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1.
J Agric Food Chem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32054270

RESUMO

D-xylose is the most abundant hemicellulosic monomer on earth, but wild-type Saccharomyces cerevisiae has very limited D-xylose uptake capacity. We conducted bioprospecting for new sugar transporters from the D-xylose-consuming filamentous fungus Trichoderma reesei and identified three candidates belonging to the major facilitator superfamily. When they were expressed in yeast and assayed for D-xylose uptake, one of them, Xltr1p, had D-xylose transport activity that was more efficient than that of Gal2p, an endogenous yeast transporter. Site-directed mutagenesis was used to examine the functional contributions of 13 amino acid residues for the uptake of D-xylose, and these experiments identified particular amino acids that function distinctly in D-xylose vs. glucose transport (e.g., F300). Excitingly, the yeast strain expressing the N326FXltr1p variant was able to carry a 'high efficiency' transporter for D-xylose but was completely unable to utilize glucose; in contrast, the strain with the F300AXltr1p variant grew on glucose but lost D-xylose transport activity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32065261

RESUMO

PURPOSE: To evaluate a radiomic approach for the stratification of diffuse gliomas with distinct prognosis and provide additional resolution of their clinicopathological and molecular characteristics. METHODS: For this retrospective study, a total of 704 radiomic features were extracted from the multi-channel MRI data of 166 diffuse gliomas. Survival-associated radiomic features were identified and submitted to distinguish glioma subtypes using consensus clustering. Multi-layered molecular data were used to observe the different clinical and molecular characteristics between radiomic subtypes. The relative profiles of an array of immune cell infiltrations were measured gene set variation analysis approach to explore differences in tumor immune microenvironment. RESULTS: A total of 6 categories, including 318 radiomic features were significantly correlated with the overall survival of glioma patients. Two subgroups with distinct prognosis were separated by consensus clustering of radiomic features that significantly associated with survival. Histological stage and molecular factors, including IDH status and MGMT promoter methylation status were significant differences between the two subtypes. Furthermore, gene functional enrichment analysis and immune infiltration pattern analysis also hinted that the inferior prognosis subtype may more response to immunotherapy. CONCLUSION: A radiomic model derived from multi-parameter MRI of the gliomas was successful in the risk stratification of diffuse glioma patients. These data suggested that radiomics provided an alternative approach for survival estimation and may improve clinical decision-making.

3.
Complement Ther Med ; 48: 102248, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987254

RESUMO

INTRODUCTION: Diabetes is closely related with depression. Gardenia fructus antidepressant formula (GFAF) is a Chinese herbal medicine that may be beneficial for depression in diabetic patients. This study aimed to evaluate the efficacy and safety of GFAF for depression in diabetes patients. METHODS: Randomized controlled trials (RCTs) were included. The patients were diagnosed as having diabetes mellitus with depression. The experimental interventions included GFAF alone or combined with another active treatment. The control interventions included no treatment, placebo or another active treatment. The primary outcome was reduction in the Hamilton Depression Scale (HAMD) scores. Secondary outcomes included reduction in the Self-rating Depression Scale (SDS) scores, response rate, adverse events, etc. PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan fang database and Chinese Science and Technology Periodicals database (VIP) were searched from inception to May 2019 for potentially eligible studies. The meta-analysis was performed using RevMan 5.3 software. RESULTS: We identified 12 eligible RCTs including 822 diabetes patients with depression. Results of meta-analysis showed that the HAMD score was significantly reduced following GFAF treatment compared with no antidepressant treatment (SMD: -2.53, 95% CI: -4.80 to -0.27, P = 0.03). Another meta-analysis indicated that patients taking GFAF alone had lower HAMD scores compared with selective serotonin reuptake inhibitors (SSRI) treatment alone (SMD: -0.62, 95% CI: -1.07 to -0.18, P = 0.006). The HAMD scores in the GFAF plus SSRI treatment group were significantly decreased compared with the SSRI treatment group (SMD: -0.37, 95% CI: -0.69 to -0.06, P = 0.02). The same pattern of change was identified with the SDS scores. CONCLUSION: GFAF may be considered an alternative treatment for depression in patients with diabetes. However, more large-scale and well-designed RCTs are warranted.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31957191

RESUMO

OBJECTIVE: The global burden of rectal gastrointestinal stromal tumor (GIST) is increasing. However, a limited number of reports hinder our ability to reach a definitive conclusion regarding the current treatment and prognosis. In this study, we outline our experience with open transanal resection of rectal GIST following neoadjuvant therapy with imatinib mesylate (IM). PATIENTS AND METHODS: We retrospectively analyzed 11 patients with rectal GISTs treated with neoadjuvant IM therapy and open transanal resection between April 2011 and April 2017 in Shanghai Changzheng Hospital. RESULTS: The patients had 400-600 mg/day IM once daily for a median of 7 months (range: 3-9 months). Tumor size, distance from the lower margin of the tumor to the anal verge (AV), mitotic rates and mutation analysis were assessed on pretreatment biopsy. After reassessment, all 11 patients underwent transanal R0 resection. With median follow-up of 28 months (range: 8-80 months), there was no tumor recurrence or metastasis. CONCLUSION: Open transanal resection of rectal GIST after neoadjuvant treatment with IM has good surgical and survival outcomes.

5.
Pathol Res Pract ; 216(1): 152754, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31787478

RESUMO

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24-0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79-0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46-6.19) and 0.39 (95 % CI = 0.28-0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04-1.6, P = 0.02) and 1.23 (95 % CI = 0.89-1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein-protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC.

6.
Biomed Res Int ; 2019: 6096350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781628

RESUMO

Purpose: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. Materials and Methods: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. Results: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. Conclusion: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1360-1366, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607284

RESUMO

OBJECTIVE: To summarize the clinical characteristics of patients with acute myeloid leukemia-type M2 (AML-M2) and analyze the factors affecting the prognosis. METHODS: One hundred eighty-eight AML-M2 patients were retrospectively analyzed for the following parameters including peripheral blood, immune phenotypes, fusion genes and cytogenetics to explore their significance for the overall survival (OS) and progression-free survival (PFS). The prognostic factors were also analyzed. RESULTS: Among 188 patients with AML-M2, the chromosomal abnormality with t (8;21), normal chromosome and other abnormalities accounted for 37% (70/188), 41% (77/188) and 22% (41/188), respectively. For the immunopheno typing of M2 patients, the hematopoietic progenitor cell differentiation antigen CD117 (96.1%) were mainly expressed, CD34 (81.6%) and HLA-DR (55.9%), and myeloid-associated antigen of CD13 (90.5%) and CD33 (89.4%) were also highly expressed. There were lymphoid-associated antigens expressed in some patients, among which the positive expression rate of CD19 was highest (29.6%), and the next was CD7 (28.5%). The most common accompanied mutations was FLT3 mutation (30.2%). The univariate analysis showed that the patients at age<50 years old, without extramedullary infiltration, with positive expression of CD19, NPM-1 (-), CEBPA double mutation(+), and HSCT were significant superior in OS and PFS (P<0.05); the multivariate analysis showed that the patient at age<50 years old, without extramedullary infiltration, with positive expression of CD19 and CEBPA double mutation (+) were significant superior in OS and PFS (P<0.05). The analysis indicated that the Karytypes affected only OS (P<0.05), while the NPM-1 gene mutation positive affected only PFS (P<0.05). The univarate analysis of factors affecting the survival in 70 AML-M2 patients with t (8;21) abnormatity showed that the C-KIT gene mutation was a poor factor for OS and PFS. CONCLUSION: The clinical characteristics are different between M2 patients with different karyotype, and prognostic analysis shows that the karytypes have an impact on overall survival; age, extramedullary infiltration, CD19 expression and CEBPA double mutation are also the main factors impacting the prognosis of patients.


Assuntos
Leucemia Mieloide Aguda , Antígenos HLA-DR , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos
8.
J Vis Exp ; (151)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31609341

RESUMO

Development of this in vivo confocal Raman spectroscopic method enables the direct measurement of water, proteins, and lipids with depth resolution in human subjects. This information is very important for skin-related diseases and characterizing skin care product performance. This protocol illustrates a method for confocal Raman spectra collection and the subsequent analysis of the spectral dataset leveraging chemometrics. The goal of this method is to establish a standard protocol for data collection and provide general guidance for data analysis. Preprocessing (e.g., removal of outlier spectra) is a critical step when processing large datasets from clinical studies. As an example, we provide guidance based on prior knowledge of a dataset to identify the types of outliers and develop specific strategies to remove them. A principal component analysis is performed, and the loading spectra are compared with spectra from reference materials to select the number of components used in the final multivariate curve resolution (MCR) analysis. This approach is successful for extracting meaningful information from a large spectral dataset.

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 412-416, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512836

RESUMO

OBJECTIVE: We aim to determine the thickness of the labial plate, the distance between the cement-enamel junction (CEJ) and alveolar crest, and the inclination angle of the long axis of healthy maxillary anterior teeth by using cone- beam computed tomography (CBCT). METHODS: A total of 345 CBCT volumes obtained by Newtom VGI® CBCT were analyzed by using the NNT software. The digital measurements of the labial bone plate thickness at level 4 mm below the CEJ, the midpoint of tooth root and the radiological tooth apex, the distance between the CEJ and alveolar crest, and the angle between the long axis of the teeth and the long axis of alveolar process were obtained from the mid-sagittal planes of maxillary incisors and canines. Plate thickness 4 mm below the CEJ was measured, and values below ≥1 mm were recorded. RESULTS: In the central incisor, 1) the angle between the long axis of the teeth and alveolar bone was 15.2°±6.2°, the distance between the CEJ and alveolar crest was (1.5±1.0) mm, labial bone plate thick-ness at 4 mm below the CEJ was (0.8±0.4) mm, the midpoint of tooth root was (0.6±0.4) mm, and the radiological tooth apex was (1.3±0.7) mm; in the lateral incisor, 16.2°±8.8°, (1.6±1.0) mm, (0.7±0.5) mm, (0.4±0.6) mm, and (1.1±0.7) mm, respectively; and in the canine, 19.0°±6.2°, (1.8±1.0) mm, (0.9±0.6) mm, (0.4±0.6) mm, and (1.2±0.7) mm, respectively. 2) The frequencies of plate thickness ≥1 mm were 28.3%, 25.8%, and 42.7% in the central incisor, lateral incisor, and canine, respectively. 3) The distance between the CEJ and alveolar crest was positively correlated with age. The correlation coefficients was 0.42 (P<0.01) in the central incisor, 0.50 (P<0.01) in the lateral incisor, and 0.62 (P<0.01) in the canine. CONCLUSIONS: The thickness of labial bone plate is thin, the distance from CEJ to alveolar crest increases with age, and the long axis of the teeth is more inclined than the long axis of alveolar process. Knowledge of these special morphological characteristics can improve the safety and result for many dental procedures.


Assuntos
Placas Ósseas , Maxila , Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Incisivo
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1033-1039, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418353

RESUMO

]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL). METHODS: The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups. RESULTS: There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P>0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037,0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770). CONCLUSION: For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.


Assuntos
Leucemia Promielocítica Aguda , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína
11.
J Alzheimers Dis ; 71(2): 559-567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424402

RESUMO

BACKGROUND: Few studies have investigated the correlation between cerebral microbleeds (CMBs), a hemorrhagic imaging marker of cerebral small vessel disease (CSVD), and brain volume. OBJECTIVE: We investigated the association between the burden and locations of CMBs and brain volume in community-dwelling populations. METHODS: Data were obtained from 1,029 participants who underwent brain magnetic resonance imaging (MRI) and APOE genotyping. Volumes of the whole brain, subcortical white matter (WM), cortical gray matter (GM), and hippocampus were extracted. Linear regression models were used to investigate the relationship between the CMB burden and their location with structural changes. RESULTS: Regarding burden, participants with≥3 CMBs had significantly lower whole brain (ß= -1.124, p = 0.0133), subcortical WM (ß= -1.020, p = 0.0043), and hippocampus (ß= -0.015, p = 0.0088) volumes than those without CMBs. Regarding location and burden, the presence of≥3 strictly lobar CMBs was negatively associated with whole brain volume (ß= -2.838, p = 0.0088). Additionally, higher CMB burdens in strictly lobar locations or deep/mixed locations were associated with lower subcortical WM volume (ß= -1.689, p = 0.0482; ß= -0.872, p = 0.0464, respectively). Finally, the presence of≥3 deep/mixed CMBs was associated with lower hippocampus volume (ß= -0.018, p = 0.0088), and these associations were independent of other ischemic markers of CSVD. However, the CMB burden and distributional pattern did not correlate with cortical GM volumes. CONCLUSION: A higher CMB burden, in specific locations, is associated with decreased brain volumes in community-dwelling populations.

12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 813-816, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400135

RESUMO

OBJECTIVE: To carry out prenatal diagnosis for a fetus with ultrasonographic abnormality. METHODS: Chromosomal karyotyping and array comparative genomic hybridization (array-CGH) analysis were applied for the diagnosis. Peripheral blood samples were also taken from the parents for chromosome karyotyping analysis. RESULTS: The fetal karyotype showed additional material of unknown-origin attached to Yq. Array CGH analysis confirmed that the material was derived from 3q22.1q29. The father was found to carry a balanced translocation 46, X, t(Y;3)(q12;q23) (which was diagnosed as 46,XY,Y≥18 elsewhere), whilst the mother was found to be normal. CONCLUSION: 3q partial trisomy may present as malformation of multiple systems. Combination of chromosome karyotyping and array-CGH can provide reliable diagnosis for fetuses with abnormalities by ultrasonography.


Assuntos
Cromossomos Humanos Par 3/genética , Diagnóstico Pré-Natal , Trissomia , Hibridização Genômica Comparativa , Feminino , Feto , Humanos , Cariotipagem , Masculino , Gravidez
13.
Chin J Integr Med ; 25(12): 887-894, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31292845

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

14.
Exp Neurobiol ; 28(3): 362-375, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31308796

RESUMO

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.

15.
Sci Rep ; 9(1): 8276, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164704

RESUMO

Epidermal growth factor receptor (EGFR) mutations are associated with response of tyrosine kinase inhibitors (TKIs) for patients with advanced non-small cell lung cancer (NSCLC). However, the existing methods for detection of samples having rare mutations(i.e. ~0.01%) have limits in terms of specificity, time consumption or cost. In the current study, novel wild-type blocking (WTB) oligonucleotides modified with phosphorothioate or inverted dT at the 5'-termini were designed to precisely detect 11 common deletion mutations in exon 19 of EGFR gene (E19del) using a WTB-PCR assay. And internal competitive leptin amplifications were further applied to enhance the specificity of the WTB-PCR system. Our results showed that WTB-PCR could completely block amplification of wild-type EGFR when 200 ng of DNA was used as template. Furthermore, the current WTB-PCR assay facilitated the detection of E19del mutations with a selectivity of 0.01% and sensitivity as low as a single copy. And, the results showed that the current WTB-PCR system exceeded detection limits afforded by the ARMS-PCR assay. In conclusion, the current WTB-PCR strategy represents a simple and cost-effective method to precisely detect various low-abundance deletion mutations.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 729-734, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204923

RESUMO

OBJECTIVE: To explore the effect and possible mechanism of PI3K/mTOR inhibitor XL765 on KG-1 cells in vitro. METHODS: The effect of XL765 on cell proliferation was detected by CCK-8 assay. The colony formation test (200 cells were plated in a plate for 9 days) was used to detect the effect of XL765 on the colony forming ability of KG-1 cells. The apoptosis was assessed by flow cytometry with Annexin V-FITC/PI double staining. Quantitative real-time polymerase chain reaction (q-PCR) was used to detect the expression of cell apoptosis-related genes BCL-2, BAX and caspase-3, Western blot was performed to detect the expression levels of BCL-2, BAX, Caspase-3, and the phosphorylation change of p-PI3K, p-AKT and p-S6K. RESULTS: XL765 effectively inhibited the proliferation and the colony formation of KG-1 cells (P=0.0002). XL765 (150 nmol/L) induced KG-1 cell apoptosis (31.87±1.376%), very statistically significant different from (3.533±0.4179% ) in the control group (P<0.01). Treatment with 150 nmol/L XL765 could in a significantly increase the expression levels of BAX and active caspase-3, and decreases expression level of the BCL-2 (P<0.01). In accordance with these results, the Western blot further confirmed the expression decrease of BCL-2 protein along with the increase BAX and cleaved caspase-3 activity. XL765 statistically significantly down-regulated the phosphorylation levels of PI3K, AKT and S6K. CONCLUSION: PI3K/mTOR inhibitor XL765 substantially suppresses KG-1 cell proliferation and induces apoptosis by inhibiting the activation of PI3K-AKT-mTOR signaling pathway, and regulating the apoptosis-related proteins.


Assuntos
Transdução de Sinais , Apoptose , Linhagem Celular Tumoral , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quinoxalinas , Sulfonamidas , Serina-Treonina Quinases TOR
17.
Insect Sci ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31207060

RESUMO

Juvenile hormone (JH) signaling plays crucial roles in insect metamorphosis and reproduction. Function of JH signaling in germline stem cells (GSCs) remains largely unknown. Here, we found that the number of GSCs significantly declined in the ovaries of Met, Gce and JHAMT mutants. Then we inhibited JH signaling in selected cell types of ovaries by expressing Met and Gce or Kr-h1 double-stranded RNAs (dsRNAs) using different Gal4 drivers. Blocking of JH signaling in muscle cells has no effect on GSC numbers. Blocking of JH signaling in cap cells reduced GSCs cells. Inductive expression of Met and Gce dsRNA but not Kr-h1 by Nos-Gal4 increased GSC cells. These results indicate that JH signaling plays an important role in GSC maintenance.

18.
Dalton Trans ; 48(22): 7583-7588, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31066420

RESUMO

In this work, with sulfur-containing ancillary ligands of triethylamine salts of bis(4-methoxyphenyl)-phosphinodithioic acid (omess) and bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphinodithioic acid (tbuss), two four-membered red iridium(iii) complexes (tfmpqz)2Ir(omess) and (tfmpqz)2Ir(tbuss) with Ir-S-P-S structures were synthesized rapidly at room temperature within 5 min, in which 4-(4-(trifluoromethyl)phenyl)quinazoline (tfmpqz) was used as the main ligand. The calculated Gibbs free energy changes of the complex formation reactions prove that they are exothermic and thermodynamically beneficial processes. Both Ir(iii) complexes show almost the same PL emissions at 624 and 623 nm with high phosphorescence quantum yields of 0.60 and 0.72, respectively. Using the two complexes as emitters, both organic light-emitting devices (OLEDs) with the structure of ITO/HATCN (hexaazatriphenylenehexacabonitrile, 5 nm)/TAPC ((bis(4-(N,N-ditolylamino)phenyl)cyclohexane, 30 nm)/(tfmpqz)2Ir(omess) or (tfmpqz)2Ir(tbuss):26DCzppy (2,6-bis-(3-(carbazol-9-yl)phenyl)pyridine) (12 wt%, 10 nm)/TmPyPB (1,3,5-tri((3-pyridyl)-phen-3-yl)benzene, 30 nm)/LiF (1 nm)/Al (100 nm) achieve good performances. Particularly, due to the introduction of tert-butyl groups into the (tfmpqz)2Ir(tbuss) complex, its device exhibits better device properties with a maximum luminance of 26 184 cd m-2, maximum current efficiency of 30.24 cd A-1, maximum power efficiency of 22.61 lm W-1 and maximum external quantum efficiency of 21.50% with CIE coordinates at (0.65, 0.34).

19.
Zhongguo Zhen Jiu ; 39(3): 267-70, 2019 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-30942013

RESUMO

OBJECTIVE: To analyze the effects of intradermal needling for pain and tear film stability in patients after pterygium excision. METHODS: A total of 76 patients (98 affected eyes) with primary pterygium were randomly divided into an observation group (38 cases, 53 affected eyes) and a control group (38 cases, 45 affected eyes).In the control group, only pterygium resection was performed, in the observation group, intradermal needling after pterygium resection was applied at Cuanzhu (BL 2), Yuyao (EX-HN 4), Taiyang (EX-HN 5), Sibai (ST 2), Hegu (LI 4), removed after 24 h and changed three times a week. The pain level of 3 days after surgery, dry eye symptoms, the basic tear secretion test (Schirmer-Ⅰ), and the tear-break time (BUT) changes before surgery, 2 weeks after surgery and 4 weeks after surgery were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: The pain level of 3 days after surgery in the observation group was significantly lower than that in the control group (P<0.05). The dry eye symptom scores at 2 weeks and 4 weeks after surgery in the two groups were significantly lower than those before surgery (all P<0.05), and the dry eye symptom scores in the observation group were significantly lower than those in the control group (both P<0.05). The Schirmer-Ⅰ test at 2 weeks and 4 weeks after surgery was significantly prolonged than that before surgery(all P<0.05), and the Schirmer-Ⅰ test in the observation group was significantly longer than that in the control group (both P<0.05). The BUT at 2 weeks and 4 weeks after surgery in the two groups was significantly longer than that before surgery (all P<0.05), and the BUT in the observation group was significantly longer than that in the control group (both P<0.05). The total effective rate in the observation group was 89.5% (34/38), which was higher than 71.1% (27/38) in the control group (P<0.05). CONCLUSION: Intradermal needling can effectively reduce the pain level of patients after pterygium resection, improve dry eye symptoms, promote the secretion of tears and improve the tear film stability.


Assuntos
Síndromes do Olho Seco , Pterígio , Pontos de Acupuntura , Humanos , Dor , Lágrimas
20.
Chem Sci ; 10(12): 3535-3542, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30996945

RESUMO

Three red cyclometalated iridium(iii) complexes (4tfmpq)2Ir(dipdtc), (4tfmpq)2Ir(dpdtc) and (4tfmpq)2Ir(Czdtc) (4tfmpq = 4-(4-(trifluoromethyl)phenyl)quinazoline, dipdtc = N,N-diisopropyl dithiocarbamate, dpdtc = N,N-diphenyl dithiocarbamate, and Czdtc = N-carbazolyl dithiocarbamate) containing the unique four-membered Ir-S-C-S backbone ring were synthesized in five minutes at room temperature with good yields, and the Gibbs free energy calculation results indicate that all reactions are exothermic and thermodynamically favorable processes. The emission colors (λ peak = 641-611 nm), photoluminescence quantum efficiencies (Φ P = 58.3-93.0%) and bipolar properties can be effectively regulated by introducing different electron-donating substituents into the dithiocarbamate ancillary ligands. Employing these emitters, organic light emitting diodes (OLEDs) with double emissive layers exhibit excellent performances with a maximum brightness over 60 000 cd m-2, a maximum current efficiency of 40.68 cd A-1, a maximum external quantum efficiency (EQEmax) of 30.54%, and an EQE of 26.79% at the practical luminance of 1000 cd m-2. These results demonstrate that Ir(iii) complexes with sulfur-containing ligands can be rapidly synthesized at room temperature, which is key to the production of metal luminescent materials for large-scale application in highly efficient OLEDs.

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