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1.
BMC Neurol ; 20(1): 48, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033580

RESUMO

BACKGROUND: The medical imaging to differentiate World Health Organization (WHO) grade II (ODG2) from III (ODG3) oligodendrogliomas still remains a challenge. We investigated whether combination of machine leaning with radiomics from conventional T1 contrast-enhanced (T1 CE) and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) offered superior efficacy. METHODS: Thirty-six patients with histologically confirmed ODGs underwent T1 CE and 33 of them underwent FLAIR MR examination before any intervention from January 2015 to July 2017 were retrospectively recruited in the current study. The volume of interest (VOI) covering the whole tumor enhancement were manually drawn on the T1 CE and FLAIR slice by slice using ITK-SNAP and a total of 1072 features were extracted from the VOI using 3-D slicer software. Random forest (RF) algorithm was applied to differentiate ODG2 from ODG3 and the efficacy was tested with 5-fold cross validation. The diagnostic efficacy of radiomics-based machine learning and radiologist's assessment were also compared. RESULTS: Nineteen ODG2 and 17 ODG3 were included in this study and ODG3 tended to present with prominent necrosis and nodular/ring-like enhancement (P < 0.05). The AUC, ACC, sensitivity, and specificity of radiomics were 0.798, 0.735, 0.672, 0.789 for T1 CE, 0.774, 0.689, 0.700, 0.683 for FLAIR, as well as 0.861, 0.781, 0.778, 0.783 for the combination, respectively. The AUCs of radiologists 1, 2 and 3 were 0.700, 0.687, and 0.714, respectively. The efficacy of machine learning based on radiomics was superior to the radiologists' assessment. CONCLUSIONS: Machine-learning based on radiomics of T1 CE and FLAIR offered superior efficacy to that of radiologists in differentiating ODG2 from ODG3.

2.
Int J Med Sci ; 17(2): 255-262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038109

RESUMO

Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1ß, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.

4.
Intest Res ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32019290

RESUMO

Background/Aims: Overwhelming evidence suggests that inflammatory bowel disease (IBD) is caused by a complicated interplay between the multiple genes and abnormal epigenetic regulation in response to environmental factors. It is becoming apparent that epigenetic factors are significantly associated with the development of the disease. DNA methylation remains the most studied epigenetic modification, and hypermethylation of gene promoters is associated with gene silencing. Methods: DNA methylation alterations may contribute to the many complex diseases development by regulating the interplay between external and internal environmental factors and gene transcriptional expression. In this study, we used 15 tumor suppressor genes (TSGs), originally identified in colon cancer, to detect promoter methylation in patients with Crohn's disease (CD). Methylation specific polymerase chain reaction and bisulfite sequencing analyses were performed to assess methylation level of TSGs in CD patients. Results: We found 6 TSGs (sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4) are robustly hypermethylated in CD patient samples. Bisulfite sequencing analysis confirmed the methylation levels of the sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4 promoters in the representative CD patient samples. Conclusions: In this study, the promoter hypermethylation of the TSGs observed indicates that CD exhibits specific DNA methylation signatures with potential clinical applications for the noninvasive diagnosis of IBD and the prognosis for patients with IBD.

5.
J Am Chem Soc ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041401

RESUMO

Oxide-/hydroxide-derived copper electrodes exhibit excellent selectivity toward C2+ products during electrocatalytic CO2 reduction reaction (CO2RR). However, the origin of such enhanced selectivity remains controversial. Here, we prepared two Cu-based electrodes with mixed oxidation states, namely HQ-Cu (containing Cu, Cu2O, CuO) and AN-Cu (containing Cu, Cu(OH)2). We extracted ultra-thin specimen from the electrodes using a focused ion beam to investigate the distribu-tion and evolution of various Cu species by electron microscopy and electron energy loss spectroscopy. We found that at the steady stage of CO2RR, the electrodes have all been reduced to Cu0, regardless of the initial states, suggesting that the high C2+ selectivities are not associated with specific oxidation states of Cu. We verified this conclusion by control experi-ments, in which HQ-Cu and AN-Cu were pretreated to fully reduce oxides/hydroxides to Cu0, and the pretreated elec-trodes showed even higher C2+ selectivity, compared with their un-pretreated counterparts. We observed that the ox-ide/hydroxide crystals in HQ-Cu and AN-Cu were fragmented into nano-sized irregular Cu grains under the applied nega-tive potentials. Such a fragmentation process, which is the consequence of an oxidation-reduction cycle and does not oc-cur in electropolished Cu, not only built an intricate network of grain boundaries, but also exposed a variety of high-index facets. These two features greatly facilitated the C-C coupling, thus accounting for the enhanced C2+ selectivity. Our work demonstrates that the use of advanced characterization techniques enables investigating the structural and chemical states of electrodes in unprecedented detail, to gain new insights into a widely studied system.

6.
BMC Med Imaging ; 20(1): 14, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041549

RESUMO

BACKGROUND: Our study aims to reveal whether the low b-values distribution, high b-values upper limit, and the number of excitation (NEX) influence the accuracy of the intravoxel incoherent motion (IVIM) parameter derived from multi-b-value diffusion-weighted imaging (DWI) in the brain. METHODS: This prospective study was approved by the local Ethics Committee and informed consent was obtained from each participant. The five consecutive multi-b DWI with different b-value protocols (0-3500 s/mm2) were performed in 22 male healthy volunteers on a 3.0-T MRI system. The IVIM parameters from normal white matter (WM) and gray matter (GM) including slow diffusion coefficient (D), fast perfusion coefficient (D*) and perfusion fraction (f) were compared for differences among defined groups with different IVIM protocols by one-way ANOVA. RESULTS: The D* and f value of WM or GM in groups with less low b-values distribution (less than or equal to 5 b-values) were significantly lower than ones in any other group with more low b-values distribution (all P <  0.05), but no significant differences among groups with more low b-values distribution (P > 0.05). In addition, no significant differences in the D, D* and f value of WM or GM were found between group with one and more NEX of low b-values distribution (all P > 0.05). IVIM parameters in normal WM and GM strongly depended on the choice of the high b-value upper limit. CONCLUSIONS: Metrics of IVIM parameters can be affected by low and high b value distribution. Eight low b-values distribution with high b-value upper limit of 800-1000 s/mm2 may be the relatively proper set when performing brain IVIM studies.

7.
Sci Adv ; 6(4): eaax5611, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32010780

RESUMO

Dysregulated physical stresses are generated during tumorigenesis that affect the surrounding compliant tissues including adipocytes. However, the effect of physical stressors on the behavior of adipocytes and their cross-talk with tumor cells remain elusive. Here, we demonstrate that compression of cells, resulting from various types of physical stresses, can induce dedifferentiation of adipocytes via mechanically activating Wnt/ß-catenin signaling. The compression-induced dedifferentiated adipocytes (CiDAs) have a distinct transcriptome profile, long-term self-renewal, and serial clonogenicity, but do not form teratomas. We then show that CiDAs notably enhance human mammary adenocarcinoma proliferation both in vitro and in a xenograft model, owing to myofibrogenesis of CiDAs in the tumor-conditioned environment. Collectively, our results highlight unique physical interplay in the tumor ecosystem; tumor-induced physical stresses stimulate de novo generation of CiDAs, which feedback to tumor growth.

8.
Chin Med J (Engl) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32049747

RESUMO

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

9.
Arch Microbiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052095

RESUMO

Invasins and intimins, members of virulence-related adhesin family which is involved in attachment and adherence to epithelial cells during infection, are found in various pathogens. These pathogens can attach to enterocytes and lead to the formation of a pedestal-like structure. Invasins and intimins belong to type Ve secretion systems, and the N-terminal ß-barrel domain acts as a translocation pore to secrete the C-terminal passenger domain. However, the relationship between invasins/intimins and type III secretion system (T3SS) has been poorly studied. Based on the transposon insertion mutant library of Edwardsiella piscicida, we got a transposon insertion mutant with significant T3SS defect and identified the mutated gene ETAE_0323 (named inV later). This gene encoded a protein with 2359 amino acid residues and was predicted to be an invasin. To study the relationship between InV and T3SS, strains with N-terminus or C-terminus deleted InV fragments were made. However, none of them was able to copy the phenotype of the transposon insertion mutant previously identified. The localization of InV in ΔT3SS strain was not significantly different from WT, suggesting that the T3SS defect in the transposon insertion mutant was likely to be caused by polar effect. Nevertheless, depletion of inV still showed dramatic internalization and virulence defect in HeLa cell and zebrafish model, respectively, suggesting InV as a virulence related protein.

10.
Int J Infect Dis ; 92: 141-150, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31931167

RESUMO

BACKGROUND: Tuberculosis (TB) treatment takes a long time, and a gold standard test to define TB cure is lacking. This may lead to early discharge of TB patients, resulting in an increased risk of disease transmission and drug resistance. Plasma lncRNAs might act as potential biomarkers to evaluate TB cure in an efficient and precise manner. METHODS: A lncRNA microarray assay was used to screen differentially expressed plasma lncRNAs in untreated TB and cured TB subjects. The expression levels of lncRNAs were verified by qPCR. Target genes of lncRNAs were predicted using a coding-non-coding gene co-expression network and mRNA-lncRNA-miRNA interaction network analysis. RESULTS: The expression levels of lncRNAs uc.48+ (p < 0.001) and NR_105053 (p = 0.03) were found to differ significantly between the untreated TB group and the cured TB group. The predicted target genes of uc.48+ were EP300, BAI1 and NR_105053 were TLR9, MYD88, BAI1, respectively. A predictive model for cured TB was established by the combination of uc.48+ and NR_105053 expression, with a sensitivity of 90.00% and specificity of 86.36%, and an area under the curve (AUC) value of 0.945. CONCLUSIONS: lncRNAs uc.48+ and NR_105053 may serve as potential biomarkers to distinguish between untreated TB patients and cured TB subjects. This study provides an experimental basis to evaluate the effect of TB treatment and may also provide new clues to the pathological mechanisms of TB.

11.
Tissue Eng Regen Med ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997256

RESUMO

BACKGROUND: The stromal vascular fraction (SVF) isolated from adipose tissue, which contains stem cells as well as other cell types, has been applied in various research fields. Although different enzymatic concentrations and treatment durations have been applied to isolate the SVF, optimal conditions have not been established. Thus, we aimed to establish the optimal conditions for isolation of the SVF from adipose tissue by automated systems. METHODS: The SVF was collected from removed adipose tissues of five donors during surgery. The SVF was treated with 0.1% or 0.2% collagenase type I for 20, 40, or 60 min. Then, colony forming unit (CFU) assays and flow cytometry were performed to characterize the adipose stem cells (ASCs). A cytokine array was used to investigate the correlation between colony-formation ability and the secretion of isolated ASCs. RESULTS: Treatment with 0.1% collagenase type I for 60 min resulted in a higher SVF yield, whereas treatment with 0.1% collagenase for 40 min resulted in higher CFU values. In addition, expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 in the SVF was higher in the high-CFU group than in the low-CFU group. CONCLUSION: The optimal conditions for isolation of the SVF from adipose tissue were treatment with 0.1% collagenase type I for 40 min. We identified the conditions required for efficient SVF isolation based on high CFU values, and our results will facilitate the development of automated systems.

12.
Oncol Res Treat ; : 1-9, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958797

RESUMO

INTRODUCTION: Platinum is widely used in the treatment of esophageal cancer. In clinical practice, it is significant to distinguish patients who respond to platinum from those who do not. Excision repair cross-complementation group 1 (ERCC1) is thought to be the key in the resistance to platinum. However, whether it is related to the platinum-based chemotherapy response on real esophageal cancer patients is controversial. We conducted this meta-analysis to explore the association between ERCC1 polymorphisms, its expression levels and platinum-based chemotherapy response, and identify the most sensitive genotypes. METHODS: The study was carried out according to the Cochrane handbook for systemic reviews of intervention. The study protocol has been registered on PROSPERO. RESULTS: Three studies were included in the analysis of C8092A polymorphisms, 5 in the C118T, and another 6 in ERCC1 expression levels. In C118T polymorphisms, compared to wild genotype, patients with mutant genotypes had a significantly higher response rate. As for C8092A polymorphisms, the mutant genotypes also presented a better response than the wild genotype. The pooled analysis indicated a significantly higher response rate in patients with a low expression of ERCC1. CONCLUSIONS: ERCC1 is a valuable biomarker for platinum-based chemotherapy in esophageal cancer. Patients with ERCC1 mutations or low-level ERCC1 expression are more sensitive to platinum-based chemotherapy.

13.
Anat Rec (Hoboken) ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909895

RESUMO

Patients with multidrug-resistant tuberculosis (MDR-TB) tend to have a long course of anti-TB treatment and severe side effects. Traditional Chinese Medicine (TCM) has a synergistic effect in attenuation of MDR-TB. However, the lack of objective biological standards to classify and diagnose MDR-TB TCM syndromes could result in less effective TCM treatment. Therefore, in this study, we identified differentially expressed proteins (DEPs) in serum of individuals with MDR-TB TCM syndromes by applying isobaric tags for relative and absolute quantification coupled with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) method and bioinformatics analysis. The functional analysis of DEPs was also performed. Additionally, DEPs among three different TCM syndromes of MDR-TB were validated by enzyme-linked immunosorbent assay (ELISA). Finally, a receiver operating characteristic (ROC) curve was performed to estimate the diagnostic ability of DEPs. A total of 71 DEPs were identified in the three different MDR-TB TCM syndrome groups such as the pulmonary Yin deficiency (PYD) syndrome group, the Hyperactivity of Fire due to Yin deficiency (HFYD) syndrome group, and the deficiency of Qi and Yin (DQY) syndrome group. The results showed that the expression level of transforming growth factor-beta-induced protein ig-h3 (TGFBI) was lower in the PYD syndrome group (p = .002), the proprotein convertase subtilisin/kexin type 9 (PCSK9) was overexpressed in the HFYD syndrome group (p < .0001), and the C-C motif chemokine ligand 14 (CCL14) expression level was reduced in the DQY syndrome group (p = .004). Our study demonstrated that serum TGFBI, PCSK9, and CCL14 may serve as potential novel biomarkers for PYD syndrome, HFYD syndrome and DQY syndrome of MDR-TB, respectively. The study provides a biological basis for MDR-TB TCM syndromes classification and can be of great significance for the treatment of different TCM syndromes.

14.
Anat Rec (Hoboken) ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909898

RESUMO

Yin-deficiency-heat (YDH) syndrome is a common sub-health state of the human body in traditional Chinese medicine (TCM). However, due to the lack of objective quantitative diagnostic indicators, patients with early-stage YDH syndrome cannot be treated in time and can develop a pathological (disease) state. Therefore, it is necessary to apply modern diagnostic techniques in order to identify the biological markers for the diagnosis of early-stage YDH syndrome. In the present study, we performed Solexa sequencing and non-targeted metabolomics analysis using high-performance liquid chromatography coupled with mass spectrometry to screen differentially expressed mRNAs and differential metabolites in individuals with early-stage YDH syndrome and healthy controls. Bioinformatics methods were used to perform enrichment analysis of differentially expressed mRNAs and differential metabolites for biological functions and signaling pathways. Furthermore, we found that differentially expressed mRNAs and differential metabolites were related to energy metabolism. Real-time PCR was used to validate the mRNA expression in the serum of subjects with early-stage YDH syndrome. We found that the mitochondrially encoded NADH dehydrogenase 2 (MT-ND2) mRNA was differentially expressed in the serum of individuals with early-stage YDH syndrome. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to evaluate the efficacy of the diagnostic model based on eight differential metabolites. We combined the three metabolites such as Glycine, Sphingomyelin, and Isocitrate to establish the diagnostic model with a sensitivity of 0.853 and a specificity of 0.800. The combination of the above three metabolites may serve as a potential biomarker for the diagnosis of early-stage YDH syndrome. Our study reveals potential biomarker for the diagnosis of early-stage YDH syndrome and also provides a new method for the quantification and objectification of TCM syndromes.

15.
Biomaterials ; 235: 119748, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978841

RESUMO

Understanding the pathways and mechanisms of human tooth decay is central to the development of both prophylaxes and treatments, but only limited information is presently available about the initiation of caries at the nanoscale. By combining atom probe tomography and high-resolution electron microscopy, we have found three distinct initial sites for human dental enamel dissolution: a) along the central dark line (CDL) within carbonated apatite nanocrystals, b) at organic-rich precipitates and c) along high-angle grain boundaries. 3D maps of the atoms within hydroxyapatite nanocrystallites in sound and naturally-decayed human dental enamel reveal a higher concentration of Mg and Na in the CDL. The CDL is therefore thought to provide a pathway for the exchange of ions during demineralization and remineralization. Mg and Na enrichment of the CDL also suggests that it is associated with the ribbon-like organic-rich precursor in amelogenesis. Organic-rich precipitates and high-angle grain boundaries were also shown to be more vulnerable to corrosion while low-angle grain boundaries remained intact. This is attributed to the lower crystallinity in these regions.

16.
Eur J Radiol ; 124: 108839, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981878

RESUMO

PURPOSE: To determine the diagnostic performance and cutoff value of two-dimensional shear wave elastography (2D SWE) for detecting significant liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: A systematic literature search of the PubMed, EMBASE, Cochrane Library databases and Web of Science was conducted. Bivariate modelling and summary receiver-operating-characteristic (ROC) modelling were constructed to summarize the diagnostic performance of 2D SWE. Meta-regression analyses were performed to explore the source of heterogeneity. RESULTS: Eleven eligible studies with 2623 patients were included. 2D SWE showed a summary sensitivity of 88 % (95 % CI: 83-91), specificity of 83 % (95 % CI: 78-88) and area under the ROC curve of 0.92 (95 % CI: 0.89-0.94) for detecting significant fibrosis in CHB patients. The mean threshold of 2D SWE was 7.91 kPa (range: 6.73-10.00 kPa). Notably, the cutoffs of studies excluding patients with history of prior antiviral therapy were generally lower than that of studies without excluding those who had received antiviral treatment, with an average of 7.15 kPa and 8.87 kPa, respectively (p < 0.01). Meta-regression analysis revealed that enrollment of consecutive patients was the only significant factor influencing heterogeneity (p < 0.01). Specifically, studies recruiting consecutive patients with CHB had significantly lower sensitivity than those with absence of consecutive enrolment (0.83 vs 0.92, p < 0.01). CONCLUSIONS: 2D SWE is an excellent modality for predicting significant liver fibrosis in CHB populations. Further work is required to establish the cutoffs that account for antiviral treatment as a potential confounding factor.

17.
Cancer Lett ; 474: 138-150, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987921

RESUMO

Mitochondrial Lon is a chaperone protein whose upregulation increases the production of mitochondrial reactive oxygen species (ROS). However, there is a lack of information in detail on how mitochondrial Lon regulates cancer metastasis through ROS production in the tumor microenvironment (TME). Our results show that elevated Lon promotes epithelial-mesenchymal transition (EMT) via ROS-dependent p38 and NF-κB-signaling. We further identified pyrroline-5-carboxylate reductase 1 (PYCR1) as a client of chaperone Lon, which induces mitochondrial ROS and EMT by Lon. Mitochondrial Lon induces ROS-dependent production of inflammatory cytokines, such as TGF-ß, IL-6, IL-13, and VEGF-A, which consequently activates EMT, angiogenesis, and M2 macrophage polarization. In addition, Lon expression is induced upon the activation and M2 polarization of macrophages, which further promotes M2 macrophages to enhance the immunosuppressive microenvironment and metastatic behaviors in the TME. This raises the possibility that manipulation of the mitochondrial redox balance in the TME may serve as a therapeutic strategy to improve T cell function in cancer immunotherapy.

18.
ACS Appl Mater Interfaces ; 12(5): 5999-6006, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944658

RESUMO

Removal of CH4 and CO2 from C2H2 streams remains challenging in the chemical industry. Herein, a robust three-dimensional metal-organic framework, Cu-CPAH, was designed and synthesized through a hydrothermal method. Cu-CPAH exhibits highly selective C2H2 adsorption capacity with respect to both CH4 and CO2, which is ascribed to the enrichment of active sites in the framework. Dynamic breakthrough results reveal that Cu-CPAH serves as a solid adsorbent for high-efficiency purification of C2H2 from an equal proportion of C2H2/CO2 or C2H2/CO2/CH4 at room temperature. Discrete Fourier transform simulations confirm that various active sites preferentially interact with C2H2 other than CO2 and CH4, signifying for the first time that the imino functional groups in the cage contribute greatly to the preferential affinity to C2H2 over CO2 and CH4.

19.
Metallomics ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31950952

RESUMO

Zinc is the second most abundant transition metal in humans and an essential nutrient required for growth and development of newborns. During lactation, mammary epithelial cells differentiate into a secretory phenotype, uptake zinc from blood circulation, and export it into mother's milk. At the cellular level, many zinc-dependent cellular processes, such as transcription, metabolism of nutrients, and proliferation are involved in the differentiation of mammary epithelial cells. Using mouse mammary epithelial cells as a model system, we investigated the remodeling of zinc homeostasis during differentiation induced by treatment with the lactogenic hormones cortisol and prolactin. RNA-Seq at different stages of differentiation revealed changes in global gene expression, including genes encoding zinc-dependent proteins and regulators of zinc homeostasis. Increases in mRNA levels of three zinc homeostasis genes, Slc39a14 (ZIP14) and metallothioneins (MTs) I and II were induced by cortisol but not by prolactin. The cortisol-induced increase was partially mediated by the nuclear glucocorticoid receptor signaling pathway. An increase in the cytosolic labile Zn2+ pool was also detected in lactating mammary cells, consistent with upregulation of MTs. We found that the zinc transporter ZIP14 was important for the expression of a major milk protein, whey acid protein (WAP), as knockdown of ZIP14 dramatically decreased WAP mRNA levels. In summary, our study demonstrated remodeling of zinc homeostasis upon differentiation of mammary epithelial cells resulting in changes in cytosolic Zn2+ and differential expression of zinc homeostasis genes, and these changes are important for establishing the lactation phenotype.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31965162

RESUMO

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In lung cancer patients with unexpected pleural metastasis detected during operation, is surgical resection of primary tumour superior to exploratory thoracotomy without resection in improving long-term survival?'. Altogether, 1443 papers were found using the reported search, of which 1 meta-analysis and 10 retrospective observational cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. One meta-analysis and 9 cohort studies found that surgical resection of the primary tumour, on the discovery of pleural metastases, yielded a better overall survival than exploratory thoracotomy alone, while 1 cohort study showed no difference. Six studies found that main tumour resection was an independent favourable prognostic factor for overall survival in lung cancer patients with unexpected pleural metastasis detected during operation, while 3 cohort studies also showed improved progression-free survival over exploratory thoracotomy. Therefore, we conclude that surgical resection of the primary tumour is superior to exploratory thoracotomy in treating lung cancer patients with unexpected pleural metastasis detected during operation.

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