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1.
Artigo em Inglês | MEDLINE | ID: mdl-32026291

RESUMO

For further understanding the genetic control mechanisms of growth and development in Tan sheep, and culturing good traits on meat performance, which is very important to both in developing local species and improving economic efficaciously. In our study, we recruited a total of 250 Tan sheep and 174 healthy Hu sheep to detect 32 SNPs in GH, GHR, NPY, Leptin, H-FABP, MSTN, and CAST by using direct sequencing techniques, in order to explore genetic marking loci which were an association with growth characters. From the results, we found different SNPs with an obvious difference for the growth traits. In the different genetic model analysis, we found SNP12, SNP29, SNP41, SNP8, SNP34, SNP35, SNP9, SNP10, SNP36, SNP45, and SNP39 were a significantly negative association with the two kinds of sheep. And SNP46, SNP42, and SNP69 with the positive association between the different trait in sheep were analyzed. From the LD and haplotype analysis, we found three blocks with the positive association in growth traits between Tan sheep and Hu sheep. The block of SNP29, SNP32, SNP34, SNP35, SNP36, SNP39, SNP41, SNP42, SNP45, and SNP46 with the genotype "AATCTACTTA" is the most significantly association with the traits. In summary, the study initially explored the genes for growth and reproduction between Tan sheep and Hu sheep and found some statistically significant results which demonstrate that there are genetic differences. These differential molecular markers may provide a scientific theoretical basis for the preferred species of Tan sheep which with good meat performance and better utilization of species resources.

2.
Anal Chim Acta ; 1101: 65-73, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32029120

RESUMO

A facile strategy was developed for the fabrication of a magnetic covalent organic framework (COF) via grafting of the monomers, 2,5-dihydroxyterephthalaldehyde (Dt) and 1,3,5-tris(4-aminophenyl) benzene (Tb) onto surface-modified Fe3O4 nanoparticles. The magnetic COF, named as magnetic COF-DtTb, was readily fabricated without high temperature or harsh reaction conditions. The synthesized magnetic COF-DtTb nanoparticles were fully characterized, presenting a regular core-shell spherical structure, large specific surface area, superparamagnetism, and good thermal stability. Their potential as an enrichment adsorbent was investigated to establish an efficient magnetic solid-phase extraction method for the determination of organophosphorus pesticide residues in fruits. Systematic method validation revealed good linearity in the concentration range of 1-200 µg L-1 (correlation coefficient >0.9957). The method limits of detection were in the range of 0.002-0.063 µg kg-1, the method limit of quantification was 1.00 µg kg-1 and recoveries ranged from 72.8% to 111% with RSDs lower than 12.3%. The results indicated that magnetic COF-DtTb possesses superior trace enrichment properties for organophosphorus pesticides in fruits.

3.
Ann Plast Surg ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32040004

RESUMO

BACKGROUND: Impaired brow function in adult patients with arteriovenous malformation is a serious disability that can even influence the field of vision. Brow reanimation techniques are used to recover a more natural appearance and brow function. Many static procedures have been set to augment brow elevation, but only dynamic procedures can lead to better functional results. In this study, the experience of a single surgeon addressing the challenge of brow restoration with dynamic procedures is presented. METHODS: A retrospective review was performed using the records of 4 adult patients who underwent dynamic procedures using a soft tissue expander for brow restoration after arteriovenous malformation excision in the unilateral site of the forehead with the expander on the contralateral side. Movement and electrodiagnostic examinations were performed postoperatively at 2 months. RESULTS: The patients included 3 males and 1 female (mean age, 20.5 ± 4.04 years). Brow improvement was noted in all patients. The results of the electrodiagnostic examination showed synchronous and spontaneous motor unit potentials and compound muscle action potentials with the contralateral forehead. CONCLUSIONS: Dynamic procedures using a soft tissue expander can provide both static and dynamic functional brow elevation of the contralateral frontalis and skin.

4.
Asian J Androl ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32031084

RESUMO

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31977645

RESUMO

PURPOSE: The purpose of this study was to explore the perceptions and experiences of patients with wound healing by secondary intention after the removal of a thoracic drainage tube. DESIGN: A qualitative phenomenological study. SUBJECTS AND SETTING: After removal of the tube, patients who were attending a nursing clinic that provides WOC care to a population of around 1 million people in Suzhou, China, were invited to participate. METHODS: Semistructured interviews were digitally audio-recorded and transcribed verbatim. Analysis of data was performed using Colaizzi's 7-step thematic analysis. RESULTS: Three major themes emerged from the interviews, namely, emotional stress response, impaired social function, and increased disease burden. CONCLUSION: Patients with wound healing by secondary intention after the removal of the drainage tube perceived they experienced an emotional stress reaction accompanied by increased psychological and economic burden. They also experienced impaired social function. There is a critical need to develop health education plans for use during the pre- and postoperative periods to reduce emotional, social, and economic consequences associated with delayed wound healing.

6.
J Food Sci ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999364

RESUMO

Salmonella enterica, Listeria monocytogenes, Shigella flexneri, Escherichia coli O157:H7, Vibrio parahaemolyticus, Staphylococcus aureus, Vibrio cholerae, Clostridium botulinum type A, Bacillus cereus, Clostridium perfringens Alpha toxin, and Yersinia enterocolitica are 11 common foodborne pathogens. Traditional bacterial culture methods for detecting pathogens are time-consuming and labor-intensive. Multiplex PCR technology, which can detect multiple targets in a single tube, has been increasingly applied to microbial detection due to its high specificity, sensitivity, and fast response. This paper is to establish a multiplex PCR technology mediated by a common primer for the detection of these 11 common foodborne pathogens in order to achieve the goal of nondirectional screening for these 11 common foodborne pathogens. The specificity of the established CP-MPCR detection system was first verified by 100 clinical isolates. The sensitivity of the CP-MPCR detection system was then detected by using cultured bacteria preparations and has been confirmed with a high sensitivity of 103 to 104 CFU/mL, among them, the sensitivity of the CP-MPCR for Vibrio cholerae and S. flexneri can even achieve 102 CFU/mL. Sixty anal swab samples collected from Suzhou CDC and 16 enrichment cultured solutions of food samples collected from the Suzhou Food Inspection and Testing Center were tested using the CP-MPCR system. A total of 32 positive results were detected. PRACTICAL APPLICATION: Food poisoning incidents occur frequently around the world, mainly because of the contamination of food by pathogenic bacteria and serious harm to human health. The method provided in this study can detect 11 foodborne pathogens in food, which can effectively prevent the spread of pathogenic microorganisms. At the same time, for the food poisoning incident that has already occurred, this method can be used for diagnosis to find out the cause.

7.
Biosens Bioelectron ; 151: 111983, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999589

RESUMO

In the last decades, enzyme mimics have been regarded as strong substitutes to natural enzymes. The construction of biosensors based on these enzyme mimics with competitive catalytic activity and substrate specificity has attracted a lot of research interest. Herein, for the first time, we investigated the capability of nanoscale FeS2 to serve as enzyme mimics. Then, a facile and effective biosensor is fabricated based on its intrinsic peroxidase-like catalytic activity. In the presence of H2O2, FeS2 nanoparticles (NPs) possess high peroxidase-like activity to 3,3',5,5'-tetramethylbenzidine (TMB) oxidation, which can be ascribed to the generation of hydroxyl radicals (·OH) from the H2O2 decomposition catalyzed by FeS2 NPs. As for TMB, the resulting Michaelis-Menten constant (Km) value of FeS2 NPs is found to be about 12 times lower than that of natural horseradish peroxidase (HRP), highlighting the superiority of FeS2 NPs. Based on these intriguing observations, a reliable colorimetric method is then developed for detection of H2O2 and glutathione (GSH) by a simple mix-and-detect strategy. The detection limits of H2O2 and GSH are as low as 0.91 µM and 0.15 µM (3σ/slope), respectively. Moreover, FeS2 NPs can also catalyse the photoluminescence (PL) substrate terephthalic acid (TA) under the assistance of H2O2. This work remarkably extends the utilization of FeS2 NPs in the construction of colorimetric and PL biosensors in the fields of biosensing, environmental monitoring, and medical diagnosis.

8.
J Appl Clin Med Phys ; 21(2): 67-72, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31925999

RESUMO

PURPOSE: To demonstrate a specific skin dose limiting technique in radiotherapy treatment planning for esophageal cancer and carry out a comparative analysis combining with clinical cases. MATERIAL AND METHODS: Thirty patients with cervical and upper thoracic esophageal carcinoma previously treated in our institution were selected. A treatment plan had been finished previously according to the planning parameters directives from physician and delivered for each patient. In this study, we copied the previously delivered plans in radiotherapy treatment planning system and converted a low dose level (usually 5Gy) to a skin dose limiting structure (SDLS), then we set the objective functions of the SDLS in the Pinnacle Inverse Planning module and re-optimize the plans to reduce the skin doses. Finally, we compared the dose distribution and other parameters of target volume and organs at risk (OARs) between the old plans and the new plans. RESULTS: There was no significant difference in most of OARs sparing. However, for all plans, the maximum dose to the SDLS decreased from 6145.90 ± 416.96 cGy to 5562.09 ± 616.69 cGy with maximum difference of 1361.30 cGy (P < 0.05), the percentage volume of 40Gy received by the SDLS decreased from (10.20 ± 6.36)% to (5.46 ± 4084)% with maximum difference of 9.89% (P < 0.05). For the target volume, there was no significant difference in the average dose and maximum dose, the approximate minimum dose to the target volume decreased from 5711.28 ± 164.61 cGy to 5584.93 ± 157.70 cGy (P < 0.05), the conformal index and homogeneity index of the target volume were hardly changed. CONCLUSION: In radiotherapy treatment planning for esophageal cancer patients, the skin dose can be significantly reduced using the skin dose limiting technique, and the impact on the dose to target volume and OARs is little, this technique can be used in most radiotherapy treatment planning.

9.
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.

10.
Chin Med J (Engl) ; 133(1): 61-67, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923105

RESUMO

BACKGROUND: Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. METHODS: This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. DISCUSSION: The tACS applied in this trial may have treatment effects on MDD with minimal side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

11.
Asian J Androl ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31929198

RESUMO

To evaluate whether prostate volume (PV) would provide additional predictive utility to the prostate health index (phi) for predicting prostate cancer (PCa) or clinically significant prostate cancer, we designed a prospective, observational multicenter study in two prostate biopsy cohorts. Cohort 1 included 595 patients from three medical centers from 2012 to 2013, and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014. Area under the receiver operating characteristic curves (AUC) and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models. Linear regression analysis showed that both total prostate-specific antigen (tPSA) and free PSA (fPSA) were significantly correlated with PV (all P < 0.05). [-2]proPSA (p2PSA) was significantly correlated with PV in Cohort 2 (P< 0.001) but not in Cohort 1 (P= 0.309), while no significant association was observed between phi and PV. When combining phi with PV, phi density (PHID) and another phi derivative (PHIV, calculated as phi/PV0.5) did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort 2. Logistic regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa (all P < 0.05); however, PV did not provide additional predictive value to phi when combining these derivatives in a regression model (all models vs phi were not statistically significant, all P > 0.05). In conclusion, PV-based derivatives (both PHIV and PHID) and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.

12.
World Neurosurg ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982596

RESUMO

OBJECTIVE: Diaphragmatic paralysis following phrenic nerve injury is an infrequent but serious condition. The destruction of respiratory function after unilateral phrenic nerve injury has been the subject of many investigations. METHODS: In this study, we used a rat model of complete paralysis of the unilateral diaphragm to observe the changes of pulmonary function. RESULTS: It is found that in the young rats of complete paralysis of the unilateral diaphragm, the vital capacity and total lung capacity show compensation after 4 weeks, and contralateral phrenic nerve transfer can enhance pulmonary function. However, in the aged rats, respiratory function parameters do not show compensation until 16 weeks after injury. CONCLUSION: These findings suggest that contralateral phrenic nerve end-to-side anastomosis is a promising therapeutic strategy. In general, our results suggest that this surgical method may hold great potential to be a secure, feasible, and effective technique to rescue diaphragmatic function.

13.
Sensors (Basel) ; 20(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941160

RESUMO

Micro-electro-mechanical system (MEMS) accelerometer-based inclinometers are widelyused to measure deformations of civil structures. To further improve the measurement accuracy, anew calibration technique was proposed in this paper. First, a single-parameter calibration modelwas constructed to obtain accurate angles. Then, an image-processing-based method was designedto obtain the key parameter for the calibration model. An ADXL355 accelerometer-basedinclinometer was calibrated to evaluate the feasibility of the technique. In this validationexperiment, the technique was proven to be reliable and robust. Finally, to evaluate theperformance of the technique, the calibrated MEMS inclinometer was used to measure thedeflections of a scale beam model. The experimental results demonstrate that the proposedtechnique can yield accurate deformation measurements for MEMS inclinometers. .

14.
Inflammation ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907686

RESUMO

Disordered glucose and lipid metabolism contributes to the progression of several liver diseases, while the upregulation of phosphatase and tensin homology deleted on chromosome ten (PTEN), a well-known tumour suppressor gene, can improve the condition through metabolic programming. This study first characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum (S. japonicum) to provide a novel clue for metabolism-targeted treatment. Compared with control mice, infected mice showed infiltrated immune cells in their livers, increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased glucose levels in their sera. The expression of key enzymes in the glycolytic pathway was significantly increased, and the expression of gluconeogenic genes was distinctly decreased. Moreover, the infection upregulated the hepatic expression of enzymes involved in fatty acid oxidation, which was consistent with the decreased number of lipid droplets in livers and the lowered levels of triglyceride in sera. Consistently, PTEN and its downstream signalling were significantly inhibited. In vitro, soluble egg antigen (SEA) downregulated the expression of PTEN in both the macrophage RAW264.7 cell line and the murine hepatocellular carcinoma HEP1-6 cell line, and induced a metabolic phenotype similar to the in vivo results. Overall, this study showed that S. japonicum infection induced the reprogramming of glucose and lipid metabolism in mice during the period of liver fibrosis and that SEA could act as a modulator to trigger such a metabolic switch in macrophages and hepatocytes. PTEN might play an essential role in mediating these metabolic reprogramming events.

15.
Acta Crystallogr D Struct Biol ; 76(Pt 1): 63-72, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31909744

RESUMO

The combination of cryo-electron microscopy (cryo-EM) and X-ray crystallography reflects an important trend in structural biology. In a previously published study, a hybrid method for the determination of X-ray structures using initial phases provided by the corresponding parts of cryo-EM maps was presented. However, if the target structure of X-ray crystallography is not identical but homologous to the corresponding molecular model of the cryo-EM map, then the decrease in the accuracy of the starting phases makes the whole process more difficult. Here, a modified hybrid method is presented to handle such cases. The whole process includes three steps: cryo-EM map replacement, phase extension by NCS averaging and dual-space iterative model building. When the resolution gap between the cryo-EM and X-ray crystallographic data is large and the sequence identity is low, an intermediate stage of model building is necessary. Six test cases have been studied with sequence identity between the corresponding molecules in the cryo-EM and X-ray structures ranging from 34 to 52% and with sequence similarity ranging from 86 to 91%. This hybrid method consistently produced models with reasonable Rwork and Rfree values which agree well with the previously determined X-ray structures for all test cases, thus indicating the general applicability of the method for X-ray structure determination of homologues using cryo-EM maps as a starting point.

17.
Eur Urol Focus ; 6(1): 53-62, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30217630

RESUMO

BACKGROUND: Accumulated evidence suggests that metastatic prostate cancer (mPCa) with a low prostate-specific antigen (PSA) level may be a unique entity. However, its clinical features and prognosis have not been fully evaluated. OBJECTIVE: To investigate the clinical features of low-PSA mPCa and the impact of low PSA level on overall survival (OS) and PCa-specific mortality (PCSM) of mPCa. DESIGN, SETTING, AND PARTICIPANTS: A total of 8479 mPCa patients were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). The median follow-up was 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression and Fine-Gray competing risk were used to calculate the hazard ratio (HR) and subdistribution hazard ratio (sHR) for OS and PCSM, respectively. RESULTS AND LIMITATIONS: A higher rate of T4 stage disease (19.8%) and visceral metastasis (18.2%) and the shortest median OS (34 mo) were observed in mPCa patients with Gleason 8-10 and PSA ≤4ng/ml. In the Cox regression model, PSA ≤4ng/ml was a significant predictor of OS for Gleason 8-10 disease. The distribution of PCSM by PSA was U-shaped for Gleason score 8-10 (PSA 4.1-10ng/ml as the referent), with an adjusted sHR of 1.52 for PSA ≤4.0ng/ml (95% confidence interval: 1.17-1.96) versus 0.99 for PSA 10.1-20ng/ml and 1.35 for PSA >20ng/ml. In contrast, the distribution of PCSM by PSA was linear for Gleason 5-7. Sensitivity analyses showed similar results in Gleason 9-10 and Gleason 10 subgroup. The study is limited by its retrospective design. CONCLUSIONS: Low PSA, high-grade mPCa has a higher proportion of T4 stage disease, visceral metastasis, and PCSM. PATIENT SUMMARY: We found that 2.8% of high-grade metastatic prostate cancer has a prostate-specific antigen level ≤4ng/ml at diagnosis. This population has aggressive clinical features and a poor cancer-specific outcome. Our results highlighted this under-reported population, and the management of these patients warrants further research.

18.
Biochem Biophys Res Commun ; 522(3): 724-730, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31791587

RESUMO

Abundant evidences have demonstrated the essential roles of long noncoding RNA (lncRNA) in the papillary thyroid cancer (PTC). Here, we aim to explore the biological roles of lncRNA SNHG1 in the PTC tumorigenesis. Firstly, we discovered the ectopically expressed ncRNAs using lncRNA microarray profiling. Among these candidate lncRNAs, SNHG1 was identified to be up-regulated in both PTC tissue and cells. Functionally, knockdown of SNHG1 repressed the proliferation, invasion and tumor growth in vitro and in vivo. Mechanistically, SNHG1 sponged miR-199a-5p by complementary binding with specificity protein 1 (SP1) 3'-UTR. Interestingly, transcription factor SP1 targeted the promoter region of SNHG1 to promote its transcriptional level. The interaction within lncRNA, miRNA and target mRNA constructed the feedback loop of SP1/SNHG1/miR-199a-5p/SP1 in PTC. Collectively, these findings unveil the potential regulation of SNHG1 on the PTC tumorigenesis via feedback loop, providing a novel insight for PTC.

19.
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.

20.
J Cell Biochem ; 121(2): 1552-1562, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31512789

RESUMO

OBJECTIVE: Serine palmitoyltransferase, long chain base subunit 1 (SPTLC1) catalyzes the first step in sphingolipid synthesis and has been implicated in the progression of various cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we investigated the expression and prognostic value of SPTLC1 in ccRCC. METHODS: Three ccRCC patient cohorts were studied. ccRCC and adjacent normal kidney tissue samples were obtained from 183 patients at the Fudan University Shanghai Cancer Center (FUSCC) and subjected to immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction to evaluate SPTLC1 protein and messenger RNA (mRNA) expression. Two validation cohorts consisting of mRNA and clinicopathological data sets from patients with ccRCC were obtained from the Cancer Genome Atlas (TCGA, n = 429) and Oncomine (n = 178) databases. Associations between low and high SPTLC1 mRNA and protein expression and survival were evaluated using the Kaplan-Meier method and log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox regression analysis. RESULTS: SPTLC1 mRNA or protein were expressed at significantly lower levels in ccRCC tissues compared with normal kidney tissues in all three patient cohorts (P < .001). Low SPTLC1 expression was significantly associated with shorter overall survival in the FUSCC (P = .041) and Oncomine (P < .001) cohorts, and was significantly associated with shorter overall survival (P < .0001) and progression-free survival (P < .001) in the TCGA cohort. Bioinformatics analysis identified 10 genes significantly coregulated with SPTLC1 in ccRCC, most of which contributed to sphingomyelin metabolism (SPTLC2, SPTLC3, SPTSSA, SPTSSB, ORMDL1, ORMDL2, ORMDL3, ZDHHC9, GOLGA7B, and KDSR). Functional enrichment analysis predicted that SPTLC1 and its network play significant roles in inflammatory, hypoxia, and interferon gamma responses, and in allograft rejection pathways. CONCLUSION: Low SPTLC1 expression is significantly associated with disease progression and poor survival in patients with ccRCC, suggesting that SPTLC1 may function as a tumor suppressor. Thus, SPTLC1 could be a potential new biomarker and/or therapeutic target for ccRCC.

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