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1.
BMC Neurosci ; 22(1): 22, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771108

RESUMO

BACKGROUND: Differences of genotypes between male and female have been studied in Parkinson's disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant. OBJECTIVE: The aim of this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD. METHODS: 613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex. RESULTS: Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135-0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167-0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361-0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228-0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428-0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078-2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102-0.849) compared with male. CONCLUSION: In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.

2.
Nurse Educ Today ; 99: 104781, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33530029

RESUMO

BACKGROUND AND OBJECTIVE: Nursing professional identity is an important factor in the development of nursing education and clinical practice. Career-planning curriculums enable students to learn relevant knowledge and skills in a targeted manner, in addition to achieve career targets. Assessment and analysis of the present situation of Chinese nursing students' career planning and professional identity may provide an important guidance for the improvement of teaching content and quality of the career-planning curriculum. This study aimed to describe nursing students' professional identity, and to find out influences of nursing students' career planning, internship experience, and other factors on professional identity. METHODS: A descriptive cross-sectional research method was employed to conduct a questionnaire on 453 full-time junior and senior undergraduate nursing students in China in December 2019. RESULTS: The average score for nursing students' professional identity was 101.42, which is at a moderately low-level. There was a significantly positive correlation between the level of nursing students' career planning and professional identity (r = 0.529, P < 0.01). Nursing students' professional identity was also influenced by grade, age, acceptance of career-planning curriculums, and other factors. CONCLUSION: The results indicated that the level of professional identity in nursing students is closely associated with their career planning. One strategy to improve this situation is to motivate universities to pay further attention to the effectiveness of career-planning curriculums and, to improve the quality of teaching and guidance system.

3.
Reprod Biol Endocrinol ; 19(1): 2, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33407571

RESUMO

BACKGROUND: The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. METHODS: ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. RESULTS: ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19. CONCLUSION: These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.

4.
Thorac Cancer ; 11(12): 3436-3447, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33107700

RESUMO

BACKGROUND: Early diagnosis improves the prognosis for non-small cell lung cancer (NSCLC); therefore, there is a pressing need for effective diagnostic methods for NSCLC. Increasing evidence indicates that serum exosomal micro RNAs (miRNAs) represent promising diagnostic and prognostic markers for multiple cancers. Here, we explored a panel of miRNAs for NSCLC diagnosis and functionally characterized miR-1269a in the pathogenesis of NSCLC. METHODS: First, we analyzed high-throughput data from The Cancer Genome Atlas (TCGA) to identify differentially expressed miRNAs between NSCLC patients and healthy controls. We examined the expression profiles of the identified miRNAs using qRT-PCR. RESULTS: We found that four micro-RNAs (hsa-miR-9-3p, hsa-miR-205-5p, hsa-miR-210-5p, and hsa-miR-1269a) were more abundant in serum exosomes from NSCLC patients. A logistic regression model validated the diagnostic efficacy of the four-microRNA panel, allowing us to distinguish NSCLC patients from healthy controls with AUCs of 0.915 and 0.878 for the training and validation sets, respectively. Functionally, NSCLC cell proliferation, migration, and invasion were affected by the aberrant expression of hsa-miR-1269a in culture. Reduced expression of miR-1269a resulted in reduced proliferation, migration, and invasion through targeting the forkhead box O1 gene (FOXO1). CONCLUSIONS: Taken together, our study identified a panel of four serum exosomal miRNAs as a potential noninvasive diagnostic biomarker for NSCLC. The interactions between FOXO1 and miR-1269a represent novel potential targets for NSCLC therapy.

5.
Theriogenology ; 158: 218-226, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32980684

RESUMO

Embryo implantation plays a decisive role in pregnancy. While in the process of implantation, microRNA (miRNA) is an important regulatory factor in the post transcriptional level. However, the role of many miRNAs in embryo implantation remained unknown. In this study, microRNA-183 (miR-183) was found differentially expressed in mouse uterus during implantation. In vivo treatment of miR-183 agomir in the uterine horn before implantation could eliminate the number of implantation site. The localization of miR-183 in mouse uteri gradually changed from epithelial to stromal layer in early pregnancy. Mice implantation models demonstrated that the decrease of miR-183 was mainly caused by maternal factors. Loss and gain function of miR-183 in endometrial cell lines showed that miR-183 could inhibit cell migration, invasion and apoptosis. MiR-183 could inhibit embryo implantation by binding Heparin-Binding EGF-like growth factor (Hbegf) and Laminin gamma one (Lamc1), which were key genes in embryo apposition and penetration. All these evidences indicate that miR-183 plays an important role during embryo implantation. This study provides new insights into the functions of miR-183 during embryo implantation and the development of contraceptive drugs in early pregnancy.

6.
J Am Chem Soc ; 142(42): 18086-18092, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32985888

RESUMO

Great attention has been paid to nanoclusters having face-centered-cubic (fcc) metal kernels, because of the similarity of metal packing to that of bulk gold. So far, there is no precedent example of an all-alkynyl-protected fcc gold nanocluster with more than 100 gold atoms. We report the synthesis and total structure determination of an alkynyl-protected gold nanocluster [NEt3H]2[Au110(p-CF3C6H4C≡C)48] (Au110). It has an fcc Au86 kernel with 24 peripheral Au(C≡CR)2 staples. The Au86 kernel consists of six close packing layers in the pattern of Au6:Au16:Au21:Au21:Au16:Au6. Electronic absorption spectroscopy shows Au110 has a molecular-like discrete electronic structure, and transient absorption experiments reveal its nonmetallic nature.

7.
Polymers (Basel) ; 12(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887279

RESUMO

In order to further understand the shape memory mechanism of a silicon dioxide/shape memory polyurethane (SiO2/SMPU) composite, the thermodynamic properties and shape memory behaviors of prepared SiO2/SMPU were characterized. Dynamic changes in the molecular orientation and interphase structures of SiO2/SMPU during a shape memory cycle were then discussed according to the small angle X-ray scattering theory, Guinier's law, Porod approximation, and fractal dimension theorem. In this paper, a dynamic mechanical analyzer (DMA) helped to determine the glass transition start temperature (Tg) by taking the onset point of the sigmoidal change in the storage modulus, while transition temperature (Ttrans) was defined by the peak of tan δ, then the test and the calculated results indicated that the Tg of SiO2/SMPU was 50.4 °C, and the Ttrans of SiO2/SMPU was 72.18 °C. SiO2/SMPU showed good shape memory performance. The programmed SiO2/SMPU showed quite obvious microphase separation and molecular orientation. Large-size sheets and long-period structures were formed in the programmed SiO2/SMPU, which increases the electron density difference. Furthermore, some hard segments had been rearranged, and their gyration radii decreased. In addition, several defects formed at the interfaces of SiO2/SMPU, which caused the generation of space charges, thus leading to local electron density fluctuations. The blurred interphase structure and the intermediate layer formed in the programmed SiO2/SMPU and there was evident crystal damage and chemical bond breakage in the recovered SiO2/SMPU. Finally, the original and recovered SiO2/SMPU samples belong to the surface fractal system, but the programmed sample belongs to the mass fractal and reforms two-phase structures. This study provides an insight into the shape memory mechanism of the SiO2/SMPU composite.

8.
J Chromatogr Sci ; 58(10): 969-975, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-32869056

RESUMO

A new capillary electrophoresis method was applied to chiral separation of three amino acids, including D,L-tryptophan, D,L-tyrosine and D,L-phenylalanine. The chiral resolution was attained in an untreated fused-sillica capillary using a dual chiral selector, which was made up of Cu(II)-L-histidine complex and ß-cyclodextrin (CD). The cardinal factors influencing its separation efficiency, such as chiral selectors, buffer pH and applied voltage, were optimized. Best results were acquired by using a buffer consisting of 10 mmol/L Cu(II), 13 mmol/L L-histidine, 8 mmol/L ß-CD, 5 mmol/L phosphate adjusted to pH 5.0 and 15 kV applied voltage. All enantiomers were entirely resolved within 20 min with high resolutions of 3.6~6.1. The analysis method was verified through the determination of D,L-tryptophan in terms of linearity, precision and accuracy. And the robustness of this method was proved. The Limit of Detection and Limit of Quantification for both enantiomers were 2.5 and 5 µg/mL, respectively. The method was perfectly applied to the determination of the enantiomeric purity of L-tryptophan. Furthermore, the interaction between Cu(II)-L-histidine complex and ß-CD was also studied using Ultraviolet-visible and 1H NMR spectroscopy to explain the synergistic effect involved. The results illustrated that Cu(II)-L-histidine complex and ß-CD played a synergistic role in the enantiomeric separation of chiral drugs, with good prospects for application.

9.
J Cell Mol Med ; 24(18): 10830-10841, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32735377

RESUMO

Overexpression of P2X7R has been observed in several tumours and is related to cancer advancement and metastasis. However, the role of P2X7R in colorectal cancer (CRC) patients is not well understood. In the current study, overexpression of P2X7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2X7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry. In this study, we found that overexpression of P2X7R increases in the in vivo growth of tumours. P2X7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2X7R up-regulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumour cells with P2X7R overexpression stimulated cytokines to recruit tumour-associated macrophage (TAMs) to increase the growth of tumours. We also found that the NF-κB signalling pathway is involved in P2X7R-induced cytokine up-regulation. P2X7R promotes NF-κB-dependent cytokine induction, which leads to TAM recruitment to control tumour growth and advancement and remodelling of the stroma. Our findings demonstrate that P2X7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.

10.
Theriogenology ; 157: 360-371, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32861000

RESUMO

The establishment of uterine receptivity is a prerequisite for embryo implantation and begins with the transformation of the luminal epithelium. MicroRNAs (miRNAs) have been widely reported to be involved in the regulation of embryo implantation, but their roles in establishing uterine receptivity remain unclear. In this study, through small RNA sequencing analysis, we showed that a low level of miR-192-5p is essential for initiating implantation in mice, and transient upregulation of miR-192-5p led to implantation failure. In situ hybridization results revealed that miR-192-5p was primarily expressed in the endometrial epithelium, and dysregulation of miR-192-5p interfered with the performance of the luminal epithelium, resulting in inadequate receptivity. By manipulating miR-192-5p expression in mouse uterus and an endometrial epithelial cell line, we showed that miR-192-5p maintains cell polarity through stabilizing adherens junction protein E-cadherin, thereby preventing epithelial-mesenchymal transition. Furthermore, miR-192-5p preserved the pattern of microvilli as well as Muc1 expression on the apical membrane of epithelial cells, thereby avoiding embryo adhesion. Moreover, miR-192-5p was found to be regulated by ovarian steroids. Collectively, this study demonstrated that the physiological role of miR-192-5p in mouse uterus is to maintain the nonreceptive state of epithelial cells and prevent their transformation to the receptive state. Thus, a sustained high level of miR-192-5p is detrimental to embryo implantation. These findings help elucidate the mechanisms involved in miRNA-based regulation of uterine physiology in early pregnancy, and may even contribute to the diagnosis and treatment of infertility.

11.
Med Sci Monit ; 26: e926441, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633271

RESUMO

BACKGROUND Hyperbilirubinemia is associated with central nervous system damage in preterm neonates due to the neurotoxicity of bilirubin. This study explored the possible mechanisms of bilirubin's neurotoxicity, and the protective effect of baicalin (BAI) was also investigated. MATERIAL AND METHODS Isolated neonatal rat hippocampal neurons were exposed to free bilirubin (Bf). BAI was used to treat these neurons. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cell viability. Terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay was used to detect apoptosis. Contents of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Protein expression and phosphorylation levels were assessed by Western blotting. Nuclear translocation was observed by immunofluorescent staining. RESULTS Bf incubation significantly induced apoptosis and decreased viabilities of neurons. The phosphorylation levels of MAP kinase kinase (MKK)3, MKK6, p38 mitogen- activated protein kinases (MAPK), nuclear translocation level of p65, and the expression levels of cleaved caspase3 and tumor necrosis factor (TNF)alpha were found to be dramatically higher in Bf-incubated neurons. BAI pre-treatment, however, increased cell viability by reducing cell apoptosis. BAI pre-treatment also reduced phosphorylation levels of MKK3, MKK6, p38 MAPK, and nuclear translocation level of p65, as well as the expression levels of cleaved caspase3 and TNFalpha, in Bf- incubated neurons. CONCLUSIONS BAI suppressed bilirubin-induced neuron apoptosis and inflammation by deactivating p38 MAPK signaling.

12.
Huan Jing Ke Xue ; 41(2): 620-629, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608720

RESUMO

Temporal evolution of black carbon (BC) in Nanjing was studied along with its main influencing factors. The multi-wavelength aethalometer (AE-33) was used to select the typical month of each season to observe BC mass concentration, combined with atmospheric pollutant data, meteorological elements, and boundary layer detection data. Seasonal, daily, weekly trends, and source characteristics of BC were analyzed. The results showed that the BC concentration in Nanjing had obvious seasonal changes, which were higher in spring and winter, in the decreasing order:spring[(3351±919) ng·m-3] > winter[(3234±2102) ng·m-3] > in autumn[(3064±967) ng·m-3] > summer[(2632±1705) ng·m-3]. The diurnal changes in BC during the four seasons are bimodal, with peaks at 06:00-08:00 and 21:00-23:00. The morning and evening peak distribution characteristics of BC in different seasons are different. The peak concentration of BC was highest in the early morning peak spring and the highest in the late peak winter. The morning peak timing of winter is 2 h behind other seasons, while the summer peak timing is 2 h ahead of other seasons. The effect of the wind speed on the seasonal distribution of BC diurnal variation is significantly larger than that on RH. The mechanism of the influence of the inversion layer on the concentration of atmospheric pollutants is complicated. The effects of height, thickness, and temperature of the inversion layer on the pollutants are different in different seasons. Weekly BC effects vary seasonally. The effect of RH and wind speed on the weekly BC effect is small, and the difference in the inversion layer is the main reason behind it. Liquid fuel combustion in Nanjing has a greater contribution to BC, whereas solid combustion contributes by a lesser extent.

13.
Sci Rep ; 10(1): 9862, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555395

RESUMO

Endometrial cancer is one of the most prevalent tumors of the female reproductive system causing serious health effects to women worldwide. Although numerous studies, including analysis of gene expression profile and cellular microenvironment have been reported in this field, pathogenesis of this disease remains unclear. In this study, we performed a system bioinformatics analysis of endometrial cancer using the Gene Expression Omnibus (GEO) datasets (GSE17025, GSE63678, and GSE115810) to identify the core genes. In addition, exosomes derived from endometrial cancer cells were also isolated and identified. First, we analyzed the differentially expressed genes (DEGs) between endometrial cancer tissues and normal tissues in clinic samples. We found that HAND2-AS1, PEG3, OGN, SFRP4, and OSR2 were co-expressed across all 3 datasets. Pathways analysis showed that several pathways associated with endometrial cancer, including "p53 signaling pathway", "Glutathione metabolism", "Cell cycle", and etc. Next, we selected DEGs with highly significant fold change and co-expressed across the 3 datasets and validated them in the TCGA database using Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we performed a survival analysis and identified four genes (TOP2A, ASPM, EFEMP1, and FOXL2) that play key roles in endometrial cancer. We found up-regulation of TOP2A and ASPM in endometrial cancer tissues or cells, while EFEMP1 and FOXL2 were down-regulated. Furthermore, we isolated exosomes from the culturing supernatants of endometrial cancer cells (Ishikawa and HEC-1-A) and found that miR-133a, which regulates expression of FOXL2, were present in exosomes and that they could be delivered to normal endometrial cells. The common DEGs, pathways, and exosomal miRNAs identified in this study might play an important role in progression as well as diagnosis of endometrial cancer. In conclusion, our results provide insights into the pathogenesis and risk assessment of endometrial cancer. Even so, further studies are required to elucidate on the precise mechanism of action of these genes in endometrial cancer.

14.
BMC Neurol ; 20(1): 114, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228519

RESUMO

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.


Assuntos
Progressão da Doença , Mesencéfalo/patologia , Ponte/patologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Paralisia Supranuclear Progressiva/diagnóstico
15.
Cells ; 9(3)2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155950

RESUMO

Synchronous communication between the developing embryo and the receptive endometrium is crucial for embryo implantation. Thus, uterine receptivity evaluation is vital in managing recurrent implantation failure (RIF). The potential roles of small extracellular vesicle (sEV) miRNAs in pregnancy have been widely studied. However, the systematic study of sEVs derived from endometrium and its cargos during the implantation stage have not yet been reported. In this study, we isolated endometrium-derived sEVs from the mouse endometrium on D2 (pre-receptive phase), D4 (receptive phase), and D5 (implantation) of pregnancy. Herein, we reveal that multivesicular bodies (MVBs) in the endometrium increase in number during the window of implantation (WOI). Moreover, our findings indicate that CD63, a well-known sEV marker, is expressed in the luminal and glandular epithelium of mouse endometrium. The sEV miRNA expression profiles indicated that miR-34c-5p, miR-210, miR-369-5p, miR-30b, and miR-582-5p are enriched during WOI. Further, we integrated the RIF's database analysis results and found out that miR-34c-5p regulates growth arrest specific 1 (GAS1) for normal embryo implantation. Notably, miR-34c-5p is downregulated during implantation but upregulated in sEVs. An implication of this is the possibility that sEVs miR-34c-5p could be used to evaluate uterine states. In conclusion, these findings suggest that the endometrium derived-sEV miRNAs are potential biomarkers in determining the appropriate period for embryo implantation. This study also has several important implications for future practice, including therapy of infertility.

16.
Oncol Lett ; 19(3): 2431-2445, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194743

RESUMO

Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using in vitro functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells in vitro and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.

17.
Nat Commun ; 11(1): 1009, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081882

RESUMO

The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1-/- driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.


Assuntos
Dano ao DNA/genética , Neoplasias Pulmonares/genética , Tumores Neuroendócrinos/genética , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Knockout , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais
18.
J Cancer ; 11(6): 1315-1324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047538

RESUMO

MicroRNA-183(miR-183) is abnormally expressed in many kinds of tumors. It participates in the initiation and development of tumors. There are many pathways regulate the expression of miR-183. The action mechanism of miR-183 in cancer is very extensive, and contradictory conclusions are often drawn. It was upregulated in 18 kinds of cancer, downregulated in 6 kinds of cancer. In addition, there are seven types of cancer, both upregulated and downregulated reports can be found. Evidence showed that miR-183 can not only directly play the role of oncogene or antioncogene, but also regulate the expression of other oncogene or antioncogene in different cancer types. In this review, we discuss the regulator of miR-183 and summarized the expression of miR-183 in different cancers. We also counted the target genes of miR-183 and the functional roles they play. Furthermore, we focused on the roles of miR-183 in cell migration, cell invasion, epithelial-mesenchymal transition (EMT) and microangiogenesis, which play the most important roles in cancer processes. It sheds light on the likely reasons why miR-183 plays different roles in various cancers. In addition, miR-183 and its downstream effectors have the potential to be promising prognostic markers and therapeutic targets in cancer.

19.
Mol Med Rep ; 20(3): 2403-2409, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257537

RESUMO

The aim of the present study was to explore the feasibility of the construction of engineered myocardial tissues in vitro with cardiomyocyte­like cells derived from bone marrow mesenchymal stem cells (BMMSCs) and a polylactic­co­glycolic acid (PLGA) polymer. The PLGA polymer was sheared into square pieces (10x10x1 mm), sterilized by Co60 irradiation, and hydrated in Dulbecco's modified Eagle's medium for 1 h. BMMSCs were isolated from the bone marrow of Sprague­Dawley rats and the third passage cells were induced by 5­azacytidine (5­aza). Following successful induction, the cells were trypsinized and suspended at a density of 1x109/ml. Then, the cell suspension was added to the PLGA scaffold and cultured for 14 days. The morphological changes of BMMSCs were observed using phase contrast microscopy. Immunofluorescence staining was used to identify the cardiomyocyte­like cells. Hematoxylin and eosin (H&E) and immunohistochemical staining were used to observe the morphology of the engineered myocardial tissues. The cell adhesion rates and scanning electron microscopy were used to observe the compatibility of the cardiomyocyte­like cells and PLGA. Transmission electron microscopy was used to view the ultrastructure of the engineered myocardial tissues. BMMSCs in primary culture presented round or short spindle cell morphologies. Following induction by 5­aza, the cells exhibited a long spindle shape and a parallel arrangement. Analysis of the cell adhesion rates demonstrated that the majority of the cardiomyocyte­like cells had adhered to the PLGA scaffolds at 24 h. H&E staining suggested that the cardiomyocyte­like cells with spindle nuclei were evenly distributed in the PLGA scaffold. Immunofluorescence staining revealed that the cardiomyocyte­like cells were positive for cardiac troponin I. Scanning electron microscopy demonstrated that the inoculated cells were well attached to the PLGA scaffold. Transmission electron microscopy indicated that the engineered myocardial tissues contained well­arranged myofilaments, desmosomes, gap junction and Z line­like structures. The present study successfully constructed engineered myocardial tissues in vitro with a PLGA polymer and cardiomyocyte­like cells derived from BMMSCs, which are likely to share various structural similarities with the original heart tissue.


Assuntos
Células-Tronco Mesenquimais/citologia , Miócitos Cardíacos/citologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Diferenciação Celular , Células Cultivadas , Masculino , Miocárdio/citologia , Ratos Sprague-Dawley
20.
J Hazard Mater ; 379: 120796, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31254789

RESUMO

Non-transfer arc assisted vacuum smelting technology is presented for the first time to recycle harmful silicon powder waste derived from diamond-wire cutting. The final yield and filling rate of silicon could reach 93.9% and 73%, respectively. The oxidation characteristics of silicon powder waste, formation mechanism of a hollow silicon block and removal efficiency of impurities were analyzed in detail to offer profound insights into a non-transfer arc granulation method. The critical conditions for continuous and efficient preparation of a solid silicon block were further confirmed through orthogonal experiments with 7.5 kW welder output power, 3 mm vertical scanning height, and 5 mm/s scanning speed. The yield of the silicon block was more than 96%. Meanwhile, the granulating process demonstrated a favorable effect on removing most impurities, such as C, Al, and Na, without introducing any other impurities. The residual impurities could be further removed by vacuum directional smelting. Given the extremely low equipment cost and huge room for improvement, this work is crucial for large-scale recovery of silicon powder waste.

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