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1.
Artigo em Inglês | MEDLINE | ID: mdl-32496449

RESUMO

BACKGROUND: Percutaneous compression of the trigeminal ganglion (PCTG) can induce significant hemodynamic perturbations secondary to the trigeminocardiac reflex (TCR). The aim of this study was to investigate the effect of atropine pretreatment on hemodynamic responses during PCTG for trigeminal neuralgia. MATERIALS AND METHODS: A total of 120 patients who received PCTG were randomly assigned to control and atropine groups that were pretreated with saline (n=60) and atropine 0.004 mg/kg intravenously (n=60), respectively. Heart rate (HR) and mean arterial pressure (MAP) were measured at 9 timepoints from before induction of anesthesia until the end of the PCTG procedure; the incidence of TCR was also observed. RESULTS: HR was higher in the atropine compared with control group from the time of skin puncture with the PCTG needle until after the procedure was completed (P<0.05). MAP was also higher in the atropine compared with control group, but only at entry of the needle into the foramen ovale until 1 minute after trigeminal ganglion compression (P<0.05). HR was reduced in both groups during entry of the needle into the foramen ovale and during ganglion compression, but less so in the atropine compared with the control group (P<0.05). MAP increased during PCTG compared with baseline in both groups, but with a larger increase in the atropine group (P<0.05). Two and 52 cases in the control group, and 6 and 1 cases in the atropine group, exhibited a TCR during entry of the needle into the foramen ovale and at ganglion compression, respectively (P<0.05). CONCLUSION: Pretreatment with atropine was effective in most patients at minimizing abrupt reduction in HR during PCTG.

2.
Adv Ther ; 37(5): 2246-2255, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32277344

RESUMO

INTRODUCTION: The present study aimed to compare the pharmacokinetic/pharmacodynamic (PK/PD) parameters of imipenem administered by two-step (50% delivered in a 30-min bolus, 50% for the following 90 min) or extended (administered continuously for 2 h) infusion. METHODS: Patients with sepsis and septic shock were prospectively enrolled and randomized into four groups. Subjects in the two-step or extended groups were given two doses of imipenem (0.5 g q6h and 1.0 g q8h). The plasma imipenem concentrations were measured at given time points after the fifth dose. The PK/PD target was defined as the achievement of a fractional time above the minimal inhibitory concentration (MIC) of > 40%. RESULTS: Thirty-five patients were eventually enrolled. No significant difference was observed in the percentage of patients achieving 40% T > MIC between the different infusion modes with the same dosage, although the two-step groups exhibited a significantly shorter Tmax compared with the extended groups (0.5 g q6h: 1.5 ± 0.8 vs. 2.0 ± 0.0 h; 1.0 g q8h: 1.0 ± 0.6 vs. 2.0 ± 0.0 h; both, p < 0.05). All four groups achieved 40% T > MIC when MIC was 0.5-4.0 µg/ml, but only regimens with a higher dose (1.0 g q8h) achieved target when MIC was 8 µg/ml. CONCLUSION: The two-step and extended regimens of imipenem are comparable to the PK/PD target in the treatment of sepsis and septic shock. A higher dose (1.0 g q8h) should be considered for target achievement at an MIC of > 8 µg/ml. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02616354.

3.
J Ultrasound Med ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125002

RESUMO

OBJECTIVES: Interventricular septal geometry and motion reflect the interaction between the ventricles, and an abnormal shape and abnormal motion are always regarded as signs of increased right ventricular or pulmonary artery pressure. During the neonatal period, there are profound changes in the cardiac circulation. The aims of this study were to quantitatively analyze neonatal septal deformations under normal physiologic conditions and evaluate the changes in association with the hemodynamic changes occurring during the transitional period. METHODS: This was a retrospective study of 114 healthy full-term neonates from birth to 14 days of age. Normalized septal curvatures were measured on left ventricular parasternal short-axis views during end diastole and end systole. The interventricular pressure gradient, ratio of ventricular volumes, septal strain, thickness, and some clinical characteristics were assessed, along with the association of these parameters with septal curvature. RESULTS: All 4 normalized septal curvatures were found to have a significant correlation with the trans-septal pressure gradient (TSPG) and the end-diastolic volume ratio of the left and right ventricles (P < .0001). The TSPG had the highest impact on septal curvature, and among the 4 curvatures, the middle end-systolic normalized septal curvature had the highest correlation with the TSPG (r2 = 0.948; P < .0001). CONCLUSIONS: There were significant correlations between septal curvature and the interventricular pressure gradient and ventricular volume ratio in healthy full-term neonates. The normalized septal curvatures gradually increased with increasing age and could be good indicators of the hemodynamic changes occurring during the transitional period.

4.
BMC Infect Dis ; 20(1): 168, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087697

RESUMO

BACKGROUND: Respiratory tract infection (RTI) in young children is a leading cause of morbidity and hospitalization worldwide. There are few studies assessing the performance for bronchoalveolar lavage fluid (BALF) versus oropharyngeal swab (OPS) specimens in microbiological findings for children with RTI. The primary purpose of this study was to compare the detection rates of OPS and paired BALF in detecting key respiratory pathogens using suspension microarray. METHODS: We collected paired OPS and BALF specimens from 76 hospitalized children with respiratory illness. The samples were tested simultaneously for 8 respiratory viruses and 5 bacteria by suspension microarray. RESULTS: Of 76 paired specimens, 62 patients (81.6%) had at least one pathogen. BALF and OPS identified respiratory pathogen infections in 57 (75%) and 49 (64.5%) patients, respectively (P > 0.05). The etiology analysis revealed that viruses were responsible for 53.7% of the patients, whereas bacteria accounted for 32.9% and Mycoplasma pneumoniae for 13.4%. The leading 5 pathogens identified were respiratory syncytial virus, Streptococcus pneumoniaee, Haemophilus influenzae, Mycoplasma pneumoniae and adenovirus, and they accounted for 74.2% of etiological fraction. For detection of any pathogen, the overall detection rate of BALF (81%) was marginally higher than that (69%) of OPS (p = 0.046). The differences in the frequency distribution and sensitivity for most pathogens detected by two sampling methods were not statistically significant. CONCLUSIONS: In this study, BALF and OPS had similar microbiological yields. Our results indicated the clinical value of OPS testing in pediatric patients with respiratory illness.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , Criança Hospitalizada , Testes Diagnósticos de Rotina/métodos , Orofaringe/microbiologia , Orofaringe/virologia , Infecções Respiratórias/diagnóstico , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
5.
Eur J Clin Microbiol Infect Dis ; 39(2): 339-343, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901114

RESUMO

The roll-out of molecular diagnostic tools continues to be the most important shift in the tuberculosis diagnostic landscape. The aim of this study was to develop a novel external quality assessment (EQA) panels for molecular TB diagnostics. In addition, we also assessed the performance of the laboratories with the EQA panels in China. Dried Mycobacterium tuberculosis (MTB) DNA in the chelex resin was designed as part of an EQA program. The storage of genomic DNA in the chelex resin layer had no effect on the stability of genomic DNA, even after 12 weeks of storage. Seventy-one laboratories have participated in EQA of molecular diagnostics for TB diagnosis in 2018. GeneXpert (74.6%, 53/71) was the most predominant molecular method, followed by GeneChip (32.3%, 23/71), MeltPro (22.5%, 16/71), and TB-LAMP (7.0%, 5/71). Out of 105 EQA panels, 103 EQA results (98.1%) achieved perfect scores, whereas the other two (1.9%) had satisfactory scores. There were a total of two false-negative results reported from two laboratories with local LAMP, respectively. In conclusion, we firstly develop feasible EQA panels for molecular diagnostics for tuberculosis in China. Our data demonstrate that a majority of participating laboratories are able to produce perfect results with molecular diagnostics in China, giving us important hints for the implementation of molecular diagnostics.

6.
Virol Sin ; 35(1): 93-102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31552611

RESUMO

Zika virus (ZIKV) causes rash, moderate fever, conjunctivitis, and arthralgia, and has serious connection with neurological complications; therefore, it is a major threat to public health. A rapid and supersensitive method for detecting anti-ZIKV antibodies in humans and animals is thus urgently required. Here, we report an NS1-based luciferase immunosorbent assay (LISA), developed to detect ZIKV-specific IgG. Fusion proteins including a reporter Nano-luciferase (NLuc) and various fragments of ZIKV NS1 protein were expressed in 293 T cells. LISA was performed using the above cell lysates containing the expressed fusion proteins. Sample panels of humans and animals infected with ZIKV were examined for sensitivity of LISA, relative to those of ZIKV RT-PCR, commercial NS1-based ELISA, and micro-neutralization (MN) assays. Specificity and potential cross-reactivity were also evaluated using various convalescent serum samples derived from patients infected with dengue virus (DENV), Japanese encephalitis virus (JEV), and hepatitis C virus (HCV). Results indicated the optimal antigenic domain for anti-ZIKV IgG detection was located within 172-352 amino acids (aa) of ZIKV NS1 protein. NS1-based LISA performs better than commercial ELISA in anti-ZIKV IgG detection. LISA was shown to be at least fourfold more sensitive than commercial ELISA, and could detect anti-ZIKV IgG in various animal hosts without the need of species-specific labeled antibody. This novel assay is potentially useful for the rapid and sensitive detection of anti-ZIKV IgG in human and animal samples.

7.
J Altern Complement Med ; 26(1): 58-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31580705

RESUMO

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.


Assuntos
Massagem , Manipulações Musculoesqueléticas , Vertigem/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/fisiopatologia , Vertigem/fisiopatologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-29994260

RESUMO

Feature selection is the process of selecting a subset of landmark features for model construction when there are many features and a comparatively few samples. The far-reaching development technologies such as biological sequencing at single cell level make feature selection a more challenging work. The difficulty lies in four facts: those features measured are in high dimension and with noise; dropouts make the data much sparse; many features are either redundant or irrelevant; and samples are not well-labeled in the experiments. Here, we propose a new model called ELF (Extract Landmark Features) to address the above challenges. ELF aims to simultaneously maximize topology maintenance to keep the pairwise relationships among samples, minimize feature redundancy to diversify the features, and maximize feature specificity to make every selected feature more representative. This makes ELF a nonlinear combinatorial optimization. To solve this difficult problem, we propose a heuristic algorithm based on greedy strategy. We show ELF's outstanding performance on two single cell RNA-seq datasets. One is the direct reprogramming from mouse embryonic fibroblasts to induced neuron and the other is hepatoblast differentiation. ELF is able to choose only hundreds of landmark genes to maintain the cells' correlativity. Topology maintenance, redundancy removal, and specificity each plays its important role in selecting landmark features and revealing cells' biological functions. In addition, ELF can be generally applied in other scenarios. We demonstrate that ELF can reveal pivotal pixel in writing region and human face in two public image datasets. We believe that ELF is a useful tool to obtain more interpretable results by revealing key features while clustering the samples well.

9.
Eur Radiol ; 30(1): 57-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31372782

RESUMO

PURPOSE: To investigate the diagnostic capability of whole-lesion (WL) histogram and texture analysis of dynamic contrast-enhanced (DCE) MRI inline-generated quantitative parametric maps using CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) to differentiate malignant from benign breast lesions and breast cancer subtypes. MATERIALS AND METHODS: From February 2018 to November 2018, DCE MRI using CDTV was performed on 211 patients. The inline-generated parametric maps included Ktrans, kep, Ve, and IAUGC60. Histogram and texture features were extracted from the above parametric maps respectively based on a WL analysis. Student's t tests, one-way ANOVAs, Mann-Whitney U tests, Jonckheere-Terpstra tests, and ROC curves were used for statistical analysis. RESULTS: Compared with benign breast lesions, malignant breast lesions showed significantly higher Ktrans_median, 5th percentile, entropy, and diff-entropy, IAUGC60_median, 5th percentile, entropy, and diff-entropy, kep_mean, median, 5th percentile, entropy, and diff-entropy, and Ve_95th percentile, diff-variance, and contrast, and significantly lower kep_skewness and Ve_SD, entropy, diff-entropy, and skewness (all p ≤ 0.011). The combination of all the extracted parameters yielded an AUC of 0.85 (sensitivity 76%, specificity 86%). kep_contrast showed a significant difference among different subtypes of breast cancer (p = 0.006). kep_skewness showed a significant difference between lymph node-positive and lymph node-negative breast cancer (p = 0.007). The IAGC60_5th percentile had an AUC of 0.71 (sensitivity 50%, specificity 91%) for differentiating between high- and low-proliferation groups of breast cancer. CONCLUSIONS: The WL histogram and texture analyses of CDTV-DCE-derived parameters may give additional information for further evaluation of breast cancer. KEY POINTS: • Inline DCE mapping with CDTV is effective and time-saving. • WL histogram and texture-extracted features could distinguish breast cancer from benign lesions accurately. • kep_contrast, kep_skewness, and IAUGC60_5th percentile could predict breast cancer subtypes, lymph node metastasis, and proliferation abilities, respectively.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Meios de Contraste , Entropia , Métodos Epidemiológicos , Feminino , Humanos , Metástase Linfática , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto Jovem
10.
Analyst ; 144(24): 7326-7335, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31663525

RESUMO

4-Mercaptopyridine (4-Mpy) is a pH reporter molecule commonly used to functionalize nanoprobes for surface-enhanced Raman spectroscopy (SERS) based pH measurements. However, nanoprobes functionalized by 4-Mpy alone have low pH sensitivity and are subject to interference by halide ions in sample media. To improve nanoprobe pH sensitivity and reliability, we functionalized gold nanoparticles (AuNPs) with both 4-Mpy and bromide ion (Br-). Br- electrostatically stabilizes protonated 4-Mpy, thus enabling sensitive SERS detection of the protonation state of 4-Mpy as a function of pH while also reducing variability caused by external halide ions. Through optimization of the functionalization parameters, including suspension pH, [4-Mpy], and [Br-], the developed nanoprobes enable monitoring of pH from 2.1 to 10 with high SERS activity and minimal interference from halide ions within the sample matrix. As a proof of concept, we were able to track nanoprobe location and image the pH distribution inside individual cancer cells. This study provides a novel way to engineer reliable 4-Mpy-functionalized SERS nanoprobes for the sensitive analysis of spatially localized pH features in halide ion-containing microenvironments.

11.
Chaos ; 29(8): 083112, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472492

RESUMO

We study numerically the evolutions of perturbations at critical points between modulational instability and stability regimes. It is demonstrated that W-shaped solitons and rogue waves can be both excited from weak resonant perturbations at the critical points. The rogue wave excitation at the critical points indicates that rogue wave comes from modulation instability with resonant perturbations, even when the baseband modulational instability is absent. The perturbation differences for generating W-shaped solitons and rogue waves are discussed in detail. These results can be used to generate W-shaped solitons and rogue waves controllably from weak perturbations.

12.
Eur J Clin Microbiol Infect Dis ; 38(10): 1961-1968, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342215

RESUMO

Mycobacterial culture remains the gold standard for detection of Mycobacterium tuberculosis (MTB) in clinical samples. However, no external quality assessment (EQA) tools exist to validate results obtained using this sophisticated method. Therefore, we developed EQA panels to assess the quality of mycobacterial culture results produced by designated TB hospitals in China. Artificial sputum containing methylcellulose was used to supplement quantified mycobacterial solutions to simulate culture-negative and culture-positive clinical sputum samples of low or high mycobacterial concentration, respectively. After storage of the quantified simulated EQA panels for 4 weeks at 4 °C, experimental bacterial quantification of the panels was again conducted, with no impact of artificial sputum on mycobacterial culture results observed. Next, 47 tuberculosis (TB) hospitals were recruited for evaluation of the EQA panels. Overall, 29 hospitals (61.7%) produced mycobacterial culture test results matching expected results for the EQA panels, while the remaining 18 (38.3%) hospitals did not. False-negative results for the low mycobacterial concentration panel sample accounted for 33 (73.3%) diagnostic errors. Compared with hospitals using solid culture methods as a control group, hospitals using the liquid culture method were less likely to produce uncertified results (aOR 0.064, 95% CI 0.005-0.770). In conclusion, we first developed then evaluated EQA panels for validation of mycobacterial culture testing in China. Our data demonstrate that approximately one-third of TB hospitals failed to produce results that met criteria for classification as certified mycobacterial culture testing providers, emphasizing the importance of quality control and quality assurance in TB diagnostics.


Assuntos
Técnicas Bacteriológicas/métodos , Testes Diagnósticos de Rotina/métodos , Ensaio de Proficiência Laboratorial/métodos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose/diagnóstico , Técnicas Bacteriológicas/normas , China , Testes Diagnósticos de Rotina/normas , Hospitais , Humanos
13.
Placenta ; 82: 17-24, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174622

RESUMO

INTRODUCTION: Invasive deficiency of the trophoblast and poor remodeling of the uterine spiral arteries were probably the primary pathogenesis causes of preeclampsia (PE). The expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) during embryogenesis had been previously confirmed and was closely related to the function of tumor cells, which was similar to the characteristics of trophoblasts. In this work, we investigated the expression profile of ROR1 in preeclampsia placentas and the functional role of ROR1 in trophoblast cells, as well as the associated molecular mechanisms. METHODS: The localization expression of ROR1 in the placenta was detected by immunohistochemistry in 20 cases of normal term pregnancy, preterm delivery, late-onset severe PE, and early-onset severe PE, respectively. The expression levels were determined by fluorescence quantitative PCR and Western blot. The influence of ROR1 on trophoblast proliferation, migration, invasion, and potential regulatory pathways was evaluated in HTR-8/SVneo cell lines by transient transfection methods. RESULTS: The levels of ROR1 in the placental tissues in PE were significantly lower than those in normal term pregnancy and preterm delivery. Moreover, the expression levels of ROR1 in early-onset severe PE were significantly lower than those in its late counterparts. ROR1 overexpression increased cell proliferation, migration, and invasion of HTR-8/SVneo cells, whereas its silencing had the opposite effect. Meanwhile, the phosphorylation levels of critical kinases in the PI3K/AKT/mTOR pathways were increased by ROR1 overexpression, whereas they were decreased by the silencing of ROR1. CONCLUSION: ROR1 might be involved in the development of PE through regulating trophoblast viability, migration, and invasion by PI3K/AKT/mTOR signaling pathway.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Regulação para Baixo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Transdução de Sinais/fisiologia , Trofoblastos/metabolismo , Linhagem Celular , Sobrevivência Celular/fisiologia , Feminino , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Serina-Treonina Quinases TOR/metabolismo , Trofoblastos/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-31145173

RESUMO

BACKGROUND: Percutaneous compression of the trigeminal ganglion (PCTG) has been used to treat trigeminal neuralgia since 1983. A PCTG-related trigeminocardiac reflex (TCR) can induce dramatic hemodynamic disturbances. This study investigates the effects of depth of propofol anesthesia on hemodynamic changes during PCTG. MATERIALS AND METHODS: A total of 120 patients who underwent PTCG for trigeminal neuralgia were randomly assigned to control group-intravenous saline pretreatment before PCTG puncture and anesthesia targeted to bispectral index (BIS) 40 to 60 throughout, and study group-intravenous propofol 1 to 2 mg/kg pretreatment to deepen anesthesia to BIS<40 before PCTG. Mean arterial pressure, heart rate (HR), cardiac output, system vascular resistance, and BIS were measured at 9 time points during the procedure, and the incidence of the TCR was observed at T5 and T6. RESULTS: BIS was lower in the study group compared with the control after pretreatment with propofol or saline, respectively. Compared with the control group, mean arterial pressure was lower in the study group at several points during the procedure, but there was no difference in HR between the 2 groups at any point. Cardiac output was higher and system vascular resistance lower in the study compared with the control group. In the control group, 42 (70.0%) and 52 (86.7%) of patients developed a TCR at the 2 points, and 37 (67.1%) and 45 (75.0%) in the study group. There was no difference in the incidence of TCR between the 2 groups. CONCLUSION: Increasing the depth of propofol anesthesia partially attenuated PTCG-related elevation of blood pressure but did not modify the abrupt reduction in HR.

15.
Biosci Rep ; 39(4)2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30962263

RESUMO

microRNAs (miRNA), as tumor suppressors or oncogenes, are involved in modulating cancer cell behavior, including cell proliferation and apoptosis. The miR-140-5p acts as a tumor suppressor in several tumors, but the role of miR-140-5p in chronic myeloid leukemia (CML) remains unclear. Here, we investigated the suppression of miR-140-5p in CML patients and CML cell lines using quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). Overexpression miR-140-5p in CML cells significantly inhibited cell proliferation as revealed by the CCK-8 assay and promoted cell apoptosis as revealed by flow cytometry. Moreover, the sine oculis homeobox 1 (SIX1) gene had been confirmed as a direct target of miR-140-5p using bioinformatics analysis and luciferase reporter assays. Overexpression of miR-140-5p decreased the SIX1 protein level in CML cells. SIX1 mRNA and protein levels were significantly up-regulated in CML patients and CML cell lines. Knockdown of SIX1 expression significantly inhibited CML cell proliferation and promoted cell apoptosis. Furthermore, SIX1 as a transcriptional factor positively regulated pyruvate kinase isozyme type M2 (PKM2) expression and played an important role in the Warburg effect. In addition, these findings indicated that miR-140-5p functions as a tumor suppressor and plays a critical role in CML cell apoptosis and metabolism by targeting SIX1. Moreover, the miR-140-5p/SIX1 axis may be a potential therapeutic target in CML.

16.
Chin Med J (Engl) ; 132(11): 1344-1353, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30939485

RESUMO

BACKGROUND: The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia. METHODS: A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 µmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3ß (GSK-3ß)/GSK-3ß, and ß-catenin/ß-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy. RESULTS: In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ±â€Š0.9 µg/g vs. 12.3 ±â€Š1.9 µg/g, P = 0.005; 6.7 ±â€Š0.6 µg/g vs. 12.3 ±â€Š1.9 µg/g, P < 0.01), increased the expression of claudin-5 (0.79 ±â€Š0.08 vs. 0.41 ±â€Š0.06, P < 0.01; 0.97 ±â€Š0.07 vs. 0.41 ±â€Š0.06, P < 0.01), and elevated the ZO-1 protein level (P < 0.05) in brain microvascular segments in a dose-dependent manner in comparison with the corresponding values in the model group. There was no significant difference in occludin expression (P > 0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3ß/GSK-3ß, and ß-catenin/ß-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05). CONCLUSION: NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3ß/ß-catenin signaling pathway.


Assuntos
Benzofuranos/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo , Animais , Barreira Hematoencefálica/ultraestrutura , Western Blotting , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Células Cultivadas , Claudina-5/metabolismo , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
17.
J Cell Biochem ; 120(9): 15083-15088, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31026090

RESUMO

Long noncoding RNA (lncRNA) PTCSC3 (hereafter PTCSC3 is used to represent lncRNA PTCSC3) inhibits glioma and thyroid cancer, indicating its potential tumor suppression function in other types of cancers. We explored the potential involvement of PTCSC3 in triple-negative breast cancer (TNBC). In the current study, we found that PTCSC3 was downregulated in tumor tissues of patients with TNBC. PTCSC3 expression was positively correlated with plasma levels of PTCSC3. LncRNA H19 was upregulated and was inversely correlated with PTCSC3 in tumor tissues. PTCSC3 overexpression led to downregulated H19 in TNBC cells, while H19 overexpression did not affect PTCSC3 expression. PTCSC3 inhibited and H19 promoted proliferation of TNBC cells. H19 overexpression attenuated the effects of PTCSC3 overexpression. Cancer cell migration and invasion were not significantly affected by PTCSC3 overexpression. Therefore, lncRNA PTCSC3 inhibits TNBC cell proliferation by downregulating lncRNA H19.

18.
Fitoterapia ; 137: 104151, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30999024

RESUMO

The norbisabolane-type sesquiterpenoids bearing a spiroketal functionality have been found in Phyllanthus spp. and showed anti-HBV activities. As part of an ongoing effort to search for promising anti-HBV sesquiterpenes from Phyllanthus plants, we report four new norbisabolane-type sesquiterpenoids, phyacidusin A (1), phyacidusin B (2), phllanthacidoid A1 (3) and phllanthacidoid N1 (4), from stem of P. acidus collected in Xishuangbanna, Yunnan province, China. The absolute configuration of new compounds was established by coupling constants and ROESY correlations, as well as comparation of NMR data with those of known compounds. The absolute configuration of new compounds 1 and 2 was further confirmed by X-ray diffraction. Compound 2 showed effect to HBsAg with an IC50 value of 11.2 ±â€¯0.01 µM, while compound 3 inhibited HBeAg secretion with an IC50 value of 57.1 ±â€¯0.02 µM. The results enriched the diversity of anti-HBV norbisabolane sesquiterpenes.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Phyllanthus/química , Sesquiterpenos/farmacologia , Antivirais/isolamento & purificação , China , Células Hep G2 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Sesquiterpenos/isolamento & purificação
19.
Vaccine ; 37(15): 2122-2130, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30851967

RESUMO

The Zika virus (ZIKV) and poxvirus infection are considered as public health emergencies, necessitating the development of effective vaccines. Here, we report novel recombinant DNA-based and non-replicating vaccinia virus (NTV)-based vaccine candidates that express the precursor membrane-envelope (prME) or envelope (E) glycoproteins of ZIKV. After immunization of BABL/c mice with the vaccines using a homologous protocol (DNA/DNA, NTV/NTV) or heterogeneous (DNA/NTV) protocol, a similar level of anti-E IgG and neutralizing antibodies (microneutralization test) were detected in the mice. However, a significantly higher level of E-specific T cell responses was elicited in mice when a heterogeneous prime-boost protocol was used (DNA/NTV) with either the DNA-based or NTV-based vaccines. Furthermore, neutralizing antibodies and a T cell immune response against the vaccinia virus (VV) were detected in mice that were subjected to the prime-boost protocol (DNA/NTV), whereas those subjected to a homologous NTV/NTV protocol had higher levels of anti-VV IgG and neutralizing antibodies. Lastly, a novel H-2d-restricted CD8 T-cell epitope, VRSYCYEASISDMAS, was identified in the ZIKV E protein. These data demonstrate proof of concept of a bivalent vaccine candidate against ZIKV and orthopoxvirus, and support the use of DNA-prME prime and NTV-E boost protocols to protect against ZIKV and orthopoxvirus infections.

20.
Phys Rev E ; 99(1-1): 012216, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30780219

RESUMO

We study the excitation conditions of antidark solitons and nonrational W-shaped solitons in a nonlinear fiber with both third-order and fourth-order effects. We show that the relative phase can be used to distinguish antidark solitons and nonrational W-shaped solitons. The excitation conditions of these well-known fundamental nonlinear waves (on a continuous-wave background) can be clarified clearly by the relative phase and three previously reported parameters (background frequency, perturbation frequency, and perturbation energy). Moreover, the numerical simulations from the nonideal initial states also support these theoretical results. These results provide an important complement for the studies on relationship between modulation instability and nonlinear wave excitations, and are helpful for controllable nonlinear excitations in experiments.

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