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1.
Chemosphere ; 246: 125820, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918111

RESUMO

[Background] Melamine and phthalates have been reported to damage renal function in children. This association is scarce in general adults. [Method] A cross-sectional subsample population of 611 adults participating in the 2012 Shanghai Food Consumption Survey (SHFCS) was analyzed for urinary biomarkers of melamine, metabolites of phthalates, and renal function parameters. The correlations between renal function parameters and chemical exposure (either independently or interactively) were explored by linear regression models. To simplify the analysis, phthalate metabolites were dimensionally reduced using principal component analysis (PCA) method. [Result] Urinary melamine was positively associated with renal function parameters of both albumin-to-creatinine ratio (ACR) and ß2-microglobulin (B2M) in multivariate linear regression models (P < 0.05). A PCA pattern characterized by high-molecular-weight phthalates (HMWP) was positively associated with all three parameters of renal function (ACR, B2M, and N-acetyl-ß-d-glucosaminidase (NAG)). The co-exposure to melamine and HMWP presented an additive effect on increasing these parameters (ACR, B2M, and NAG). [Conclusion] Impaired renal function in Shanghai adults was associated with exposure to both melamine and HMWP.

2.
Endocr Relat Cancer ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905165

RESUMO

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR-positive and HR-negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR- HER2-positive breast tumors to understand their molecular heterogeneity. Sixty-four HR+/HER2+ and forty-three HR-/HER2+ stage I-III breast cancer patients were included in the study. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76%, 61% and 49%, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations, and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P=0.004), TGF-beta (P=0.007) and WNT (P=0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

3.
Org Lett ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31908172

RESUMO

In this work, an interesting and practical procedure for the synthesis of 1,2-diketones from aryl halides and organoaluminum reagents has been developed. Employing tert-butyl isocyanide as the CO source and palladium as the catalyst, the desired 1,2-diketones were isolated in good to excellent yields with good functional group tolerance. Concerning the reaction partners, besides aryl halides, both alkyl- and arylaluminum reagents were all suitable substrates here.

4.
Ecol Lett ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912600

RESUMO

Although interspecific competition has long been recognised as a major driver of trait divergence and adaptive evolution, relatively little effort has focused on how it influences the evolution of intraspecific cooperation. Here we identify the mechanism by which the perceived pressure of interspecific competition influences the transition from intraspecific conflict to cooperation in a facultative cooperatively breeding species, the Asian burying beetle Nicrophorus nepalensis. We not only found that beetles are more cooperative at carcasses when blowfly maggots have begun to digest the tissue, but that this social cooperation appears to be triggered by a single chemical cue - dimethyl disulfide (DMDS) - emitted from carcasses consumed by blowflies, but not from control carcasses lacking blowflies. Our results provide experimental evidence that interspecific competition promotes the transition from intraspecific conflict to cooperation in N. nepalensis via a surprisingly simple social chemical cue that is a reliable indicator of resource competition between species.

5.
Mikrochim Acta ; 187(2): 109, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915938

RESUMO

An in-situ approach is described for synthesis of poly(sulfobetaine-co-polyhedral oligomeric silsesquioxane) [poly(sulfobetaine-co-POSS)] that can be used in a hybrid monolithic column as a hydrophilic liquid chromatography (HILIC) stationary phase. Synthesis involves (a) radical polymerization of octa(propyl methacrylate)-polyhedral oligomeric silsesquioxane (MA-POSS) and organic monomers such as dimethylaminopropyl methacrylate or vinyl imidazole, and (b) in-situ ring-opening quaternization between 1,4-butane sultone and the organic monomers. The sulfobetaine groups are generated in-situ monolith. This obviates the need for synthesis of sulfobetaine monomer previously. The pore size and permeability of the material can be tuned by using a binary porogenic system (polyethyleneglycol 600 and acetonitrile) and via the composition of the polymerization mixture. The optimized hybrid monolith owns its merits to the presence of POSS and sulfobetaine groups with good mechanical stability, the lack of residual silanol groups, and adequate hydrophilicity. The column filled with the monoliths was evaluated as a stationary phase for HILIC. Several kinds of polar compounds (including nucleosides, bases, phenols, aromatic acids and amides) were separated by using mobile phases with high organic solvent fractions in capillary liquid chromatography. Graphical abstractAn in-situ approach is described for synthesis of poly(sulfobetaine-co-polyhedral oligomeric silsesquioxane) hybrid monolithic column for use in hydrophilic liquid chromatography. The optimized monolith owns good mechanical stability, the lack of residual silanol groups and adequate hydrophilicity. Baseline separation of several kinds of polar compounds is achieved on the column. MA-POSS: octa(propyl-methacrylate) polyhedral oligomeric silsesquioxane; DMAEMA: dimethylaminoethyl methacrylate; AIBN: azodiisobutyronitrile. Poly(DMABS-co-POSS): poly(N-(4-sulfobutyl)-N-methacryloxypropyl- N,N-dimethylammonium-betaine-co-polyhedral oligomeric silsesquioxane).

6.
Artif Cells Nanomed Biotechnol ; 48(1): 435-442, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31916466

RESUMO

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

7.
BMJ Open ; 10(1): e033230, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900273

RESUMO

INTRODUCTION: Stair ascent and descent require complex integration between sensory and motor systems; individuals with knee osteoarthritis (KOA) have an elevated risk for falls and fall injuries, which may be in part due to poor dynamic postural control during locomotion. Tai chi exercise has been shown to reduce fall risks in the ageing population and is recommended as one of the non-pharmocological therapies for people with KOA. However, neuromuscular mechanisms underlying the benefits of tai chi for persons with KOA are not clearly understood. Postural control deficits in performing a primary motor task may be more pronounced when required to simultaneously attend to a cognitive task. This single-blind, parallel design randomised controlled trial (RCT) aims to evaluate the effects of a 12-week tai chi programme versus balance and postural control training on neuromechanical characteristics during dual-task stair negotiation. METHODS AND ANALYSIS: Sixty-six participants with KOA will be randomised into either tai chi or balance and postural control training, each at 60 min per session, twice weekly for 12 weeks. Assessed at baseline and 12 weeks (ie, postintervention), the primary outcomes are attention cost and dynamic postural stability during dual-task stair negotiation. Secondary outcomes include balance and proprioception, foot clearances, self-reported symptoms and function. A telephone follow-up to assess symptoms and function will be conducted at 20 weeks. The findings will help determine whether tai chi is beneficial on dynamic stability and in reducing fall risks in older adults with KOA patients in community. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (#2018KY-006-1). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800018028.

8.
J Synchrotron Radiat ; 27(Pt 1): 217-221, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31868755

RESUMO

Time-resolved X-ray excited optical luminescence (TR-XEOL) was developed successfully for the 23A X-ray nanoprobe beamline located at the Taiwan Photon Source (TPS). The advantages of the TR-XEOL facility include (i) a nano-focused X-ray beam (<60 nm) with excellent spatial resolution and (ii) a streak camera that can simultaneously record the XEOL spectrum and decay time. Three time spans, including normal (30 ps to 2 ns), hybrid (30 ps to 310 ns) and single (30 ps to 1.72 µs) bunch modes, are available at the TPS, which can fulfil different experimental conditions involving samples with various lifetimes. It is anticipated that TR-XEOL at the TPS X-ray nanoprobe could provide great characterization capabilities for investigating the dynamics of photonic materials.

9.
Neurosci Lett ; 717: 134722, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31877334

RESUMO

Epidemiological evidence of the relationship between vitamin D receptor (VDR) rs2228570 (FokI) polymorphism and the susceptibility of Parkinson's disease (PD) is inconsistent, partially due to between-study variations in sample size, age, male/female ratio, and 25-OH vitamin D3 levels. Here, we examined the association between VDR rs2228570 polymorphism and PD risk in a Chinese population. A total of 940 subjects were included in this study, which consisted of 470 patients with sporadic PD (mean age: 62.65 ±â€¯9.34 years) and 470 healthy control subjects (mean age: 62.70 ±â€¯9.42 years). A TaqMan genotyping assay was applied to identify VDR rs2228570 polymorphism. The Hardy-Weinberg Equilibrium (HWE) was calculated for both groups with a Chi-square (χ2) test. The sample power was calculated with Power V3.0. The crude odds ratios (ORs) and 95 % confidence intervals (CIs) for sporadic PD in relation to VDR rs2228570 polymorphism were calculated using a logistic regression analysis. The minor A allele frequency was 0.42 and 0.48 in the control and PD groups, respectively. A allele carriers of rs2228570 were associated with an increased overall risk of PD as well as early-onset PD (EOPD) in the allele and additive genetic models. Stratification analyses showed similar results in male subjects in the allele and additive genetic models, but only in the additive genetic model in female subjects. In conclusion, our study suggests that the VDR rs2228570 A allele is associated with an increased risk of PD in a Chinese population. Further investigations with larger sample sizes with consideration of gene-gene and gene-environment interaction are needed to further elucidate the role of vitamin D receptors in the development of PD.

10.
Emerg Infect Dis ; 26(1): 164-166, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855545

RESUMO

We investigated the epidemiology of cholera in Taiwan during 2002-2018. Vibrio cholerae sequence type (ST) 75 clone emerged in 2009 and has since become more prevalent than the ST69 clone from a previous pandemic. Closely related ST75 strains have emerged in 4 countries and may now be widespread in Asia.

11.
Mar Drugs ; 17(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835449

RESUMO

To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas. To improve the chitinase production, one-factor-at-a-time and orthogonal test approaches were adopted to optimize the medium components and culture conditions. The results showed that the highest chitinolytic activity (6.36 times higher than that before optimization) was obtained with 95.41 U L-1 with 15 g L-1 of glucose, 1 g L-1 of peptone, 15 g L-1 of colloid chitin and 0.25 g L-1 of magnesium ions contained in the medium, cultivated under pH 7.0 and a temperature of 20 °C. To better understand the application potential of this strain, the enzymatic properties and the antifungal activity of the crude chitinase secreted by the strain were further investigated. The crude enzyme showed the maximum catalytic activity at 35 °C and pH 4.5, and it also exhibited excellent low-temperature activity, which still displayed more than 50% of its maximal activity at 0 °C. Furthermore, the crude chitinase showed significant inhibition of fungi Verticillium dahlia CICC 2534 and Fusarium oxysporum f. sp. cucumerinum CICC 2532, which can cause cotton wilt and cucumber blight, respectively, suggesting that strain GWSMS-1 could be a competitive candidate for biological control in agriculture, especially at low temperature.

12.
J Pharmacol Toxicol Methods ; : 106662, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837439

RESUMO

The quantification and visualization of fluorescent staining at the whole organ level remain a challenge. Deconvolution image systems allow multi-dimensional imaging and stereo-measurement via rapid 3D reconstruction. To demonstrate this technique, we investigated doxorubicin-induced cardiotoxicity in zebrafish. Fluorogenic probe and immunofluorescence were employed to identify cardiac reactive oxygen species generation and myocardial apoptosis, respectively. We revealed the spatial distribution of fluorescent staining across the whole heart by this approach. In addition, the fluorescence intensities and fluorescence-dyed volumes in the zebrafish heart were quantified automatically. Importantly, doxorubicin treatment induced more ROS generation in the ventricle as compared to the atrium, while the levels of activated caspase-3 were much higher in the atrioventricular junction. These results would have been difficult to observe using traditional 2D images. Therefore, our deconvolution imaging strategy allows the 3D quantification and visualization of fluorescent staining at the whole organ level, and will thus support in vivo studies.

13.
Nano Lett ; 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838853

RESUMO

Magnetic topological insulator, a platform for realizing quantum anomalous Hall effect, axion state and other novel quantum transport phenomena, has attracted a lot of interest. Recently, it is proposed that MnBi2Te4 is an intrinsic magnetic topological insulator, which may overcome the disadvantages in the magnetic doped topological insulator, such as disorder. Here we report on the gate-reserved anomalous Hall effect (AHE) in the MnBi2Te4 thin film. By tuning the Fermi level using the top/bottom gate, the AHE loop gradually decreases to zero and the sign is reversed. The positive AHE exhibits distinct coercive fields compared with the negative AHE. It reaches a maximum inside the gap of the Dirac cone, and its amplitude exhibits a linear scaling with the longitudinal conductance. The positive AHE is attributed to the competition of the intrinsic Berry curvature and the extrinsic skew scattering. Its gate-controlled switching contributes a scheme for the topological spin field-effect transistors. Keywords: magnetic topological insulator, anomalous Hall effect, sign reversal, Berry curvature, skew scattering.

14.
Sci Adv ; 5(12): eaax7537, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31840067

RESUMO

The efficiencies of small-pixel perovskite photovoltaics have increased to above 24%, while most reported fabrication methods cannot be transferred to scalable manufacturing process. Here, we report a method of fast blading large-area perovskite films at an unprecedented speed of 99 mm/s under ambient conditions by tailoring solvent coordination capability. Combing volatile noncoordinating solvents to Pb2+ and low-volatile, coordinating solvents achieves both fast drying and large perovskite grains at room temperature. The reproducible fabrication yields a certified module efficiency of 16.4%, with an aperture area of 63.7 cm2. This method can be applied for various perovskite compositions. The perovskite modules also show a small temperature coefficient of -0.13%/°C and nearly fully recoverable efficiency after 58 cycles of shading, much better than commercial silicon and thin-film solar modules.

15.
Environ Int ; 135: 105363, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31830728

RESUMO

Melamine is widely used to make household products including plates, cups, and large-scale industrial plastic products. Studies have shown the nephrotoxicity of melamine. However, little is known about urinary melamine concentration in adults and its association with the consumption of foods, other than milk products. In this study, we measured the urinary melamine concentration of 908 Shanghai adults and calculated the estimated daily intake (EDI) and hazard quotient accordingly. We also used a 24 h (24-hr) recall survey to identify possible risk foods associated with melamine exposure. Melamine was detectable in over 85% of the urine samples and had a median concentration of 2.524 µg/g. There were 22 participants who had EDIs exceeding the tolerable daily intake (TDI) of 3150 ng/kg bw/day, the strictest reference dose in administration by far. Melamine concentration in urine was positively associated with the 24-hr recall consumption of rice, fruits, beef, mutton, processed meats, and eggs, but no other food categories. Our study provides evidence-based data on the melamine exposure level in adults from Shanghai, China, and some possible associations with food intake.

16.
Int J Mol Sci ; 20(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31817029

RESUMO

A triphenylmethane reductase derived from Citrobacter sp. KCTC 18061P was coupled with a glucose 1-dehydrogenase from Bacillus sp. ZJ to construct a cofactor self-sufficient bienzyme biocatalytic system for dye decolorization. Fed-batch experiments showed that the system is robust to maintain its activity after 15 cycles without the addition of any expensive exogenous NADH. Subsequently, three different machine learning approaches, including multiple linear regression (MLR), random forest (RF), and artificial neural network (ANN), were employed to explore the response of decolorization efficiency to the variables of the bienzyme system. Statistical parameters of these models suggested that a three-layered ANN model with six hidden neurons was capable of predicting the dye decolorization efficiency with the best accuracy, compared with the models constructed by MLR and RF. Weights analysis of the ANN model showed that the ratio between two enzymes appeared to be the most influential factor, with a relative importance of 54.99% during the decolorization process. The modeling results confirmed that the neural networks could effectively reproduce experimental data and predict the behavior of the decolorization process, especially for complex systems containing multienzymes.

17.
Am J Surg ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31818425

RESUMO

BACKGROUND: Optimal management for papillary thyroid microcarcinoma (PTMC) remains controversial. The purpose of this study was to explore risk factors predictive of cervical lymph node metastasis in conventional PTMCs. METHODS: Conventional PTMC patients (n = 2,404) undergoing surgery between 2010 and 2017 were grouped and analyzed according to the positivity of cervical lymph node. RESULTS: Central lymph node (CLN) metastases and lateral lymph node (LLN) metastases were observed in 915 (38.1%) and 184 (7.7%) cases, respectively. Multivariate analysis found that male (odds ratio [OR] = 1.974, p < 0.001), younger age (OR = 1.601, p < 0.001), tumor size (OR = 1.935, p < 0.001), extrathyroidal extension (ETE) (OR = 1.647, p < 0.001), multifocality (OR = 1.416, p < 0.001), and intrathyroidal spreading (OR = 3.355, p < 0.001) predicted increased CLN metastasis. In particular, younger age, multifocality, and intrathyroidal spreading were significantly associated with a high number of CLN metastases (n ≥ 5). The presence of CLN metastasis was strongly associated with LLN metastasis (OR = 5.426, p < 0.001). CONCLUSION: Male, younger age, tumor size, ETE, multifocality, and intrathyroidal spreading predict increased CLN metastasis in PTMCs. In patients with suspicious lateral lymphadenopathy, the presence of CLN metastasis is independently associated with LLN metastasis.

18.
Mod Pathol ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822801

RESUMO

Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma, prevalent in Asia and Latin America. Studies in Asian cohorts have identified some recurrent gene mutations in ENKTL; however, the mutational landscape of ENKTL in Latin America is unknown. In this study, we investigated the mutational profile and EBV strains of 71 ENKTL cases from Latin America (42 from Mexico, 17 from Peru, and 12 from Argentina) and compared it with Asian cohorts. The mutational analysis was performed by next generation sequencing (NGS) using an Ion AmpliSeq™ custom panel covering for the most frequently mutated genes identified in ENKTL. STAT3 was the most frequent mutated gene (16 cases: 23%), followed by MSN (10 cases; 14%), BCOR (9 cases; 13%), DDX3X (6 cases; 8%), TP53 (6 cases; 8%), MGA (3 cases; 4%), JAK3 (2 cases; 3%), and STAT5B (1 case; 1%). Mutations in STAT3, BCOR, and DDX3X were nearly mutually exclusive, suggesting different molecular pathways involved in the pathogenesis of ENKTL; whereas mutations in MGA, MSN, and TP53 were concomitant with other mutations. Most cases (75%) carried Type A EBV without the 30-bp LMP1 gene deletion. The overall survival was significantly associated with serum LDH level, Eastern Cooperative Oncology Group (ECOG) performance status, International Prognostic Index (IPI) score, and therapy (p < 0.05), but not associated with any mutation, EBV strain or deletion in EBV LMP1 gene. In conclusion, mutational analysis of ENKTL from Latin America reveals frequent gene mutations leading to activation of the JAK-STAT pathway (25%), mostly STAT3. Compared to Asian cohorts, BCOR, DDX3X and TP53 mutations were also identified but with different frequencies. None of these mutations were associated with prognosis.

19.
Front Oncol ; 9: 1310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824866

RESUMO

A mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated immune prognostic signature (IPS) for predicting prognosis in LGGs. IDH1 mutation status and RNA expression were investigated in two different public cohorts. To develop an IPS, LASSO Cox analysis was conducted for immune-related genes that were differentially expressed between IDH1wt and IDH1mut LGG patients. Then, we systematically analyzed the influence of the IPS on the immune microenvironment. A total of 41 immune prognostic genes were identified based on the IDH1 mutation status. A four-gene IPS was established and LGG patients were effectively stratified into low- and high-risk groups in both the training and validation sets. Stratification analysis and multivariate Cox analysis revealed that the IPS was an independent prognostic factor. We also found that high-risk LGG patients had higher levels of infiltrating B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells, and expressed higher levels of CTLA-4, PD-1 and TIM-3. Moreover, a novel nomogram model was established to estimate the overall survival in LGG patients. The current study provides novel insights into the LGG immune microenvironment and potential immunotherapies. The proposed IPS is a clinically promising biomarker that can be used to classify LGG patients into subgroups with distinct outcomes and immunophenotypes, with the potential to facilitate individualized management and improve prognosis.

20.
Aging (Albany NY) ; 112019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790361

RESUMO

Clinical trials testing Janus kinase-1 (JAK1) inhibitors in cancers are under way. Whether the JAK1 mRNA levels in breast tumors correlates with outcome has not been evaluated. JAK1 expression was analyzed via the Oncomine database and Tumor IMmune Estimation Resource site. Tumor tissues from 57 breast cancer patients were used for qRT-PCR and immune infiltration assessment. JAK1 expression was significantly lower in breast invasive carcinoma compared with adjacent normal tissues. Public databases (Kaplan-Meier plotter and PrognoScan) showed that low JAK1 expression was associated with poorer survival. Data from The Cancer Genome Atlas (TCGA) showed that high JAK1 expression was associated with increased survival in both TNM I-II and TNM III-IV patients. JAK1 was inversely correlated with tumor size status, lymph node status, and TNM of breast cancer patients. JAK1 levels were correlated with the T cell transcript-enriched LYM metagene signature and was significantly lower in the low tumor infiltrating lymphocytes (TILs) group. JAK1 expression levels had significant positive correlations with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in breast cancer and not with other B cells. In conclusion, JAK1 mRNA levels were correlated with prognosis and immune infiltrating levels in breast cancer.

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