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1.
Int J Mol Med ; 44(5): 1943-1951, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31573046

RESUMO

S­allyl­cysteine sulfoxide (alliin) is the main organosulfur component of garlic and its preparations. The present study aimed to examine the protective effect of alliin on cardiac function and the underlying mechanism in a mouse model of myocardial infarction (MI). Notably, alliin treatment preserved heart function, attenuated the area of infarction in the myocardium of mice and reduced lesions in the myocardium, including cardiomyocyte fibrosis and death. Further mechanistic experiments revealed that alliin inhibited necroptosis but promoted autophagy in vitro and in vivo. Cell viability assays showed that alliin dose­dependently reduced the necroptotic index and inhibited the expression of necroptosis­related receptor­interacting protein 1, receptor­interacting protein 3 and tumor necrosis factor receptor­associated factor 2, whereas the levels of Beclin 1 and microtubule­associated protein 1 light chain 3, which are associated with autophagy, exhibited an opposite trend upon treatment with alliin. In addition, the level of peroxisome proliferator­activated receptor γ was increased by alliin. Collectively, these findings demonstrate that alliin has the potential to protect cardiomyocytes from necroptosis following MI and that this protective effect occurs via the enhancement of autophagy.

2.
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.

3.
Pain Pract ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31505082

RESUMO

The objective of the present analysis was to determine whether changes in Brief Pain Inventory (BPI) average pain by patient global impression of improvement (PGI-I) category and the cut-off for clinically important difference (CID) were different between Asian and Caucasian patients with chronic pain due to osteoarthritis. This analysis used data from 3 (Caucasian) and 2 (Asian) randomized, placebo-controlled, 10- to 14-week duloxetine studies for the treatment of patients aged ≥40 years with osteoarthritis pain. The receiver operating characteristic (ROC) analysis was used to characterize the association between changes in BPI average pain and PGI-I levels at study endpoint. The CID was characterized by PGI-I and the cut-off point for CID in BPI average pain was determined by the intersection of a 45̊ tangent line with each ROC curve. Data from 668 Asian and 868 Caucasian patients were available for analysis. Baseline BPI average pain ratings including worst and least pain were comparable between Asians and Caucasians. Ratings for percentage change from baseline to endpoint for BPI average pain in Asian patients and Caucasian patients were similar across the 7 PGI-I categories, regardless of age, gender, study, and treatment. The ROC analysis results of cut-off points in BPI average pain demonstrated the raw change cut-off was -3.0, and percentage change cut-off was -40% for both Asian and Caucasian patients. Overall, the present analysis concludes changes in BPI average pain by PGI-I category and the cut-off for CID were similar for Asian and Caucasian patients with chronic pain due to osteoarthritis.

4.
Biomolecules ; 9(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547161

RESUMO

The herbicide fomesafen has the advantages of low toxicity and high selectivity, and the target of this compound is protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4). However, this herbicide has a long residual period and can have phytotoxic effects on succeeding crops. To protect maize from fomesafen, a series of thiazole phenoxypyridines were designed based on structure-activity relationships, active substructure combinations, and bioisosterism. Bioassays showed that thiazole phenoxypyridines could improve maize tolerance under fomesafen toxicity stress to varying degrees at a dose of 10 mg·kg-1. Compound 4i exhibited the best effects. After being treated by compound 4i, average recovery rates of growth index exceeded 72%, glutathione content markedly increased by 167% and glutathione S-transferase activity was almost 163% of fomesafen-treated group. More importantly, after being treated by compound 4i, the activity of PPO, the main target enzyme of fomesafen, recovered to 93% of the control level. The molecular docking result exhibited that the compound 4i could compete with fomesafen to bind with the herbicide target enzyme, which consequently attained the herbicide detoxification. The present work suggests that compound 4i could be developed as a potential safener to protect maize from fomesafen.

5.
J Arthroplasty ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31474324

RESUMO

BACKGROUND: Prior studies have compared fixed-bearing unicompartmental knee arthroplasty (FB-UKA) with mobile-bearing UKA (MB-UKA), suggesting that both procedures have good clinical outcomes. However, which treatment is more beneficial for patients is controversial. The purpose of our study is to evaluate the postoperative outcomes, including the revision rate, complications, functional results, range of motion, and femoral-tibial angle, between the 2 procedures. METHODS: We searched the MEDLINE, EMBASE, Cochrane Library, and Web of Science databases starting from August 2017 to May 2018. The publication date of articles was not restricted. Before we submit our contribution, we have re-searched it again. Articles that directly compared the postoperative outcomes of the 2 prosthesis type were included. RESULTS: A total of 15 comparative studies were included in our meta-analysis. The pooled data indicated no differences between the 2 operation modes in terms of revision rates, complications, and knee function, but earlier failure occurred more frequently with the MB design. CONCLUSION: Both the arthroplasty types provided satisfactory clinical results for patients with classic indications. However, MB-UKA tended to fail in early postoperative years whereas fixed-bearing UKA in later postoperative years. Therefore treatment options should be carefully considered for each patient, and surgeons should still use their personal experience when deciding between these options.

6.
Sci Rep ; 9(1): 13975, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562391

RESUMO

Polyetheretherketone (PEEK) is a new material used for the frameworks of removable partial dentures (RPD). The questions whether the PEEK framework has similar stress distribution on oral tissue and displacement under masticatory forces as titanium alloy (Ti-6Al-4V) or cobalt-chromium alloy (CoCr) remain unclear and worth exploring. A patient's intraoral data were obtained via CBCT and master model scan. Four RPDs were designed by 3Shape dental system, and the models were processed by three-dimensional finite element analysis. Among three materials tested, PEEK has the lowest maximum von Mises stress (VMS) on periodontal ligament (PDL), the greatest maximum VMS on mucosa, the maximum displacement on free-end of framework, and the lowest maximum VMS on framework. Results suggested that PEEK framework has a good protective effect on PDL, suggesting applications for patients with poor periodontal conditions. However, the maximum displacement of the free-end under masticatory force is not conducive for denture stability, along with large stress on the mucosa indicate that PEEK is unsuitable for patients with more loss of posterior teeth with free-end edentulism.

7.
J Prosthodont Res ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31395520

RESUMO

PURPOSE: To compare the effects of airborne-particle abrasion protocols on the surface morphology, the phase transformation and the resin bond strength of highly translucent zirconia (M) and conventional zirconia (Z). METHODS: Thirteen groups (N = 12) of Z and M specimens were prepared. Except for the control group, the specimens were sandblasted with conditions involving different grit sizes (50 µm or 110 µm), treatment times (10 s or 20 s) and pressures (0.1 MPa, 0.3 MPa or 0.6 MPa). The surface morphology was analyzed using scanning electron microscope (SEM) and the phase analysis was conducted with X-ray diffraction (XRD). The Ra and the shear bond strength (SBS) were measured and statistically analyzed, and the failure mode was determined by optical microscope. RESULTS: The surface morphologies were strongly dependent on treatment conditions. Larger particle size and higher pressure resulted in higher Ra for both materials. Longer blasting time resulted in higher Ra for Z but not M. Overall, the SBS increased with increasing Ra; the highest average SBS was achieved by M and exceeded 18 MPa. The monoclinic transformation was not found in any treatment for M, but was found in Z. CONCLUSIONS: Z and M showed different dependence on the airborne-particle abrasion parameters in terms of Ra, SBS and phase transformation. The conditions for maximizing SBS included a 110 µm particle size and 20 s treatment for both, with pressures of 0.3 MPa and 0.6 MPa for the M and Z, respectively.

8.
Cancer Biomark ; 26(1): 69-77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306108

RESUMO

Growing evidence have revealed the serum exosomal miRNAs emerged as biomarkers for various cancer types, including colorectal cancer (CRC). Here, we sought to explore the potential clinical significance of serum exosomal miR-150-5p in CRC. A total of 133 CRC patients and 60 healthy volunteers as control group were recruited in this study. Exosomes were isolated from the serum of all the participants. The total RNA was isolated from the exosomes and the serum exosomal miR-150-5p levels were measured by quantitative reverse transcription-polymerase chain reaction. The findings showed that the serum exosomal miR-150-5p levels were significantly reduced in CRC cases compared with those in the control group. Serum exosomal miR-150-5p levels in post-operative blood samples were greatly upregulated one month after surgical treatment. In addition, decreased serum exosomal miR-150-5p expression was closely correlated with poorly differentiation, positive lymph node metastasis and advanced TNM stage. Moreover, receiver operating characteristic (ROC) curve analysis showed serum exosomal miR-150-5p level had good performance to identify CRC cases from healthy volunteers, and a combination of serum exosomal miR-150-5p and carcinoembryonic antigen (CEA) could improve the diagnostic accuracy with an increased the area under the ROC curve (AUC) value. Furthermore, the survival time of patients with higher serum exosomal miR-150-5p expression was significantly longer than those with lower expression. Serum exosomal miR-150-5p was confirmed as an independent prognostic indicator in CRC. Mechanistically, ZEB1 was identified as a direct downstream target of miR-150-5p. Collectively, serum exosomal miR-150-5p might be a novel noninvasive biomarker for CRC diagnosis and prognosis.

9.
Med Sci Monit ; 25: 4575-4582, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31219101

RESUMO

BACKGROUND Retinoblastoma is a rare malignancy arising from the immature cells of the retina, generally in children up to the age of 3 years. Here, we assessed the anticancer effects of a natural sesquiterpene lactone - 8-deoxylactucin - on the growth of the retinoblastoma RB355 and normal RPE cells. MATERIAL AND METHODS Cell viability was assessed by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assessed by DAPI staining and annexin V/propidium iodide (PI) assay. Reactive oxygen species (ROS) levels were determined by fluorescence microscopy. Flow cytometry was used to determine the cell cycle distribution. Protein expression was determined by Western blot analysis. RESULTS The results showed that 8-deoxylactucin exerted selective and potent anticancer effects on the RB355 cells and exhibited an IC50 of 25 µM. Nonetheless, the cytotoxic effects of 8-deoxylactucin on the normal RPF cells were comparatively lower, as evident from the IC50 of 65 µM. 8-Deoxylactucin increased the production of ROS and triggering apoptosis of RB355 cells. The induction of 8-deoxylactucin-induced apoptosis was also accompanied with increased cleavage of caspase 3, upregulation of Bax, and downregulation of Bcl-2. The 8-deoxylactucin-induced cell cycle arrest of RB355 cells was also associated with inhibition of cyclin A and B1 expression, as well as the inhibition of Cdc2 phosphorylation. CONCLUSIONS 8-Deoxylactucin inhibits the growth of RB355 cells by apoptosis, cell cycle arrest, and increased production of ROS.

10.
Insect Sci ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215133

RESUMO

Hylyphantes graminicola is a resident spider species found in maize and cotton fields and is an important biological control agent of various pests. Previous studies have demonstrated that stress from elevated CO2 and Wolbachia infection can strongly affect spider species. Thus, based on CO2 levels (400 ppm, current atmospheric CO2 concentration and 800 ppm, high CO2 concentration) and Wolbachia status (Wolbachia-infected, W+ and Wolbachia-uninfected, W- ), we divided H. graminicola individuals into four treatment groups: W- 400 ppm, W- 800 ppm, W+ 400 ppm, and W+ 800 ppm. To investigate the effects of elevated CO2 levels (W- 400 vs W- 800), Wolbachia infection (W- 400 vs W+ 400), and the interactions between these two factors (W- 400 vs W+ 800), high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and identify stress-related differentially expressed genes (DEGs). De novo assembly of complementary DNA sequences generated 86 688 unigenes, 23 938 of which were annotated in public databases. A total of 84, 21, and 157 DEGs were found among W- 400 vs W- 800, W- 400 vs W+ 400, and W- 400 vs W+ 800, respectively. Functional enrichment analysis revealed that metabolic processes, signaling, and catalytic activity were significantly affected by elevated CO2 levels and Wolbachia infection. Our findings suggest that the impact of elevated CO2 levels and Wolbachia infection on the H. graminicola transcriptome was, to a large extent, on genes involved in metabolic processes. This study is the first description of transcriptome changes in response to elevated CO2 levels and Wolbachia infection in spiders.

11.
Acta Pharmacol Sin ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253937

RESUMO

The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC50 value of 744.3 nM. This compound bound to CBP BrD with a KD value of 4.01 µM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC50 value of 19.2 µM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein.

12.
Muscle Nerve ; 60(2): 192-201, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31093982

RESUMO

INTRODUCTION: We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. METHODS: Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. RESULTS: In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. DISCUSSION: These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.


Assuntos
4-Aminopiridina/farmacologia , Lesões por Esmagamento/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Bloqueadores dos Canais de Potássio/farmacologia , Remielinização/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Animais , Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Proteína Forkhead Box O1/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Camundongos , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/genética , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Regeneração/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Proteínas com Motivo Tripartido/efeitos dos fármacos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética
13.
PLoS One ; 14(5): e0216562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075129

RESUMO

BACKGROUND: Acute pancreatitis (AP) is associated with high complications. Early, reliable prediction of mortality may improve patient management. METHODS: We retrospectively reviewed medical records of 1,599 patients with AP treated at a single large hospital in southwest China. Models to predict mortality were derived from a subset of 1,062 patients (development dataset), and the models were then validated in the remaining 537 patients (validation dataset). Independent risk factors and prediction models for mortality were identified using logistic regression. RESULTS: A total of 33 patients in the development dataset and 13 in the validation dataset died during hospitalization. Independent risk factors for mortality were found to be plasma urea levels, glucose levels and platelet counts at admission; as well as peak urea levels, leukocyte counts and use of invasive ventilation during hospitalization. Based on the development dataset, a mortality prediction model based only on urea level at admission gave an area under the curve (AUC) of 0.81, which did not significantly improve by incorporating glucose level or platelet count at admission. Significantly better was a model taking into account three in-hospital parameters: peak urea level, leukocyte count and use of invasive ventilation (AUC 0.97). CONCLUSIONS: While mortality of AP patients can be predicted reasonably well based only on urea values at admission, predictions are more reliable when they take into account in-hospital data on peak urea level, leukocyte count and use of invasive ventilation.

14.
BMC Musculoskelet Disord ; 20(1): 174, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31010413

RESUMO

BACKGROUND: The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. METHODS: This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. RESULTS: Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was - 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was - 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. CONCLUSION: The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase. TRIAL REGISTRATION: ClinicalTrials.gov identification number NCT01931475 . Registered 29 August 2013.


Assuntos
Analgésicos/administração & dosagem , Artralgia/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Cloridrato de Duloxetina/administração & dosagem , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Analgésicos/efeitos adversos , Artralgia/diagnóstico , Artralgia/etiologia , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Método Duplo-Cego , Esquema de Medicação , Cloridrato de Duloxetina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Medição da Dor , Resultado do Tratamento
15.
Quintessence Int ; 50(5): 378-386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30957112

RESUMO

OBJECTIVE: The current design methods for the surface texture of prostheses are unsatisfactory: the line-drawing method relies heavily on the subjective experience of technicians, and the powder-coating method requires high costs. A new innovative method is proposed: curvature-analysis with reverse engineering. The objective was to compare operation times and esthetic parameters in generating surface textures among the three methods. METHOD AND MATERIALS: Twenty-seven patients with maxillary central incisor fixed dental prostheses were randomly divided into three groups, and prostheses were built by three technicians using line-drawing, powder-coating, or curvature-analysis methods, respectively. Porcelain grinding times were recorded. The final prostheses were analyzed regarding the three-dimensional deviation from the control group that used the contralateral tooth. A senior technician and clinician made a single-blind evaluation of the prostheses' surface texture. RESULTS: In the curvature-analysis method, large, medium, and small curvatures effectively showed an intrinsic labial surface, the developmental groove, and other surface morphology structures, respectively. Operation times in the line-drawing, powder-coating, and curvature-analysis methods were 19.51 ± 0.95, 16.87 ± 1.30, and 12.41 ± 0.94 minutes, respectively, with statistically significant differences among the three methods; evaluation scores were statistically significantly different between the line-drawing and curvature-analysis methods. The three-dimensional deviation root mean square values were 0.451 ± 0.083, 0.396 ± 0.029, and 0.295 ± 0.080 mm, respectively, indicating curvature analysis had the smallest three-dimensional deviation. CONCLUSIONS: Curvature analysis helps manufacture the surface texture accurately with enhanced efficiency, improving esthetics and reducing operation time and material waste.

16.
J Pharmacol Exp Ther ; 369(3): 473-480, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952680

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with progressive airflow limitation and functional decline. The pathogenic mechanisms for this disease include oxidative stress, inflammatory responses, disturbed protease/antiprotease equilibrium, apoptosis/proliferation imbalance, senescence, autophagy, metabolic reprogramming, and mitochondrial dysfunction. The Wnt signaling pathway is an evolutionarily conserved signaling pathway that is abnormal in COPD, including chronic bronchitis and pulmonary emphysema. Furthermore, Wnt signaling has been shown to modulate aforementioned cellular processes involved in COPD. From this perspective, we provide an updated understanding of the crosstalk between Wnt signal and these cellular processes, and highlight the crucial role of the Wnt signal during the development of COPD. We also discuss the potential for targeting the Wnt signal in future translational and pharmacological therapeutics aimed at prevention and treatment of this disease.

17.
Hepatol Res ; 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30945380

RESUMO

AIM: The expression of microRNA143HG (miR143HG) was significantly downregulated in hepatocellular carcinoma (HCC) tissues by bioinformatics analysis. This study aimed to determine the role of miR143HG in HCC cell proliferation and metastasis. METHODS: Fifty patients with HCC were divided into two groups based on median miR143HG expression levels. The correlation between miR143HG expression and prognosis, and the correlations between miR143HG expression and the patients' clinicopathological characteristics were evaluated based on the two groups. Gain-of-function and loss-of-function measurements of miR143HG were carried out to verify the biological function of miR143HG by Cell Counting Kit-8, EdU, Transwell, and western blotting assays and flow cytometric analysis. The underlying mechanism was explored by quantitative real-time polymerase chain reaction of miRNA (miR-155-5p and miR-26b-5p), luciferase reporter assay, western blotting of Wnt signaling pathway-related proteins (ß-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3ß (GSK3ß), ZEB1, and E-cadherin), mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (extracellular signal-regulated kinase [ERK]1/2, p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, P38, and p-P38), and immunofluorescence staining of ß-catenin. RESULTS: miR143HG expression was markedly downregulated in HCC tissues and cells. Its expression was associated with the presence or absence of portal vein tumor thrombus, hepatitis B virus infection, relapse and metastasis, and Barcelona Clinic Liver Cancer stage. Additionally, miR143HG expression predicted a good prognosis and acted as an independent prognostic factor in HCC for overall survival. Overexpression of miR143HG suppressed HCC cell proliferation and metastasis, and induced cell cycle arrest and apoptosis. Consistently, the depletion of miR143HG resulted in the opposite phenomenon of the aforementioned results. miR143HG inhibits miR-155 expression; miR-155 directly targets APC, which is a negative regulator of the Wnt/ß-catenin pathway, so miR143HG can act on the Wnt pathway. miR143HG was further found to reduce the expression of ß-catenin and block the nuclear accumulation of ß-catenin, ultimately inhibiting the activation of the Wnt pathway. It inhibits the expression of Wnt downstream target gene ZEB1, and then E-cadherin expression is increased and cell motility is inhibited. Furthermore, miR143HG exerts its antiproliferative function by influencing the MAPK signaling pathway and then inducing G2 /M arrest in cells. CONCLUSION: This study showed that miR143HG plays critical roles in the development and progression of HCC by suppressing the MAPK and Wnt signaling pathways.

18.
Phys Rev Lett ; 122(1): 017001, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31012685

RESUMO

With spin-orbit coupling, both local-moment magnetism and itinerant electrons are expected to behave anisotropically in spin space, but such effects' influence on the formation of unconventional superconductivity has been hitherto unexplored. Here, in an iron-based superconductor, Sr_{1-x}Na_{x}Fe_{2}As_{2}, we report spectroscopic evidence that itinerant electrons "prefer" to be assisted by c-axis polarized magnetic excitations in their formation of superconducting Cooper pairs, against the polarization of the local-moment excitations. Our result naturally explains why the superconductivity competes strongly with the tetragonal magnetic phase in this material, and provides a fresh view on how to make a good superconductor out of a magnetic "Hund's metal."

19.
Chemosphere ; 224: 316-323, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826701

RESUMO

Aspergillus niger (A. niger) and Syngonium podophyllum (S. podophyllum) have been used for wastewater treatment, and have exhibited a promising application in recent years. To determine the effects of A. niger on uranium enrichment and uranium stress antagonism of S. podophyllum, the S. podophyllum-A. niger combined system was established, and hydroponic remediation experiments were carried out with uranium-containing wastewater. The results revealed that the bioaugmentation of A. niger could increase the biomass of S. podophyllum by 5-7%, reverse the process of U(VI) reduction induced by S. podophyllum, and increase the bioconcentration factor (BCF) and translocation factor (TF) of S. podophyllum to uranium by 35-41 and 0.01-0.06, respectively, thereby improving the reduction of uranium in wastewater. Moreover, A. niger could promote the cell wall immobilization and the subcellular compartmentalization of uranium in the root of S. podophyllum, reduce the phytotoxicity of uranium entering root cells, and inhibit the calcium efflux from root cells, thereby withdrawing the stress of uranium on S. podophyllum.


Assuntos
Araceae/crescimento & desenvolvimento , Aspergillus niger/metabolismo , Urânio/análise , Águas Residuárias/química , Poluentes Radioativos da Água/análise , Purificação da Água/métodos , Araceae/metabolismo , Biodegradação Ambiental , Biomassa , Hidroponia , Minerais , Urânio/metabolismo , Poluentes Radioativos da Água/metabolismo
20.
J Clin Pharmacol ; 59(6): 890-899, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30861159

RESUMO

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for CYP3A4 20230T>C (rs2242480), CYP3A4 T>C (rs4646437), CYP3A5*3 6898A>G (rs776746), ABCB1 129T>C (rs3213619); ABCB1 c.1236C>T (rs01128503), ABCB1 c.2677G>T/A (rs2032582) and ABCB1 c.3435C>T (rs1045642) polymorphisms, and the effects of gene-gene and gene-environment interactions on the predictive accuracy of algorithm were evaluated. In wild-type CYP3A4 rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P < 1 × 10-4 ). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild-type CYP3A5 rs776746 carriers who had hypertension were higher than those without hypertension (P = 4.10 × 10-3 ). More importantly, dose-predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.

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