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1.
Chemosphere ; 240: 124789, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561157

RESUMO

Poly- and perfluorinated compounds (PFCs) may induce potential endocrine-disrupting hormonal effects. However, the molecular mechanism of the toxicology of PFCs remains unclear, and the insufficient information is available on the biological activities of PFCs at present. In this study, the cell-based reporter gene assays were used to determine the agonistic activity of PFCs on the human pregnane X receptor (hPXR). The heuristic method combined with best subset modeling (HM-BSM) based on Dragon descriptors and comparative similarity indices analysis (CoMSIA) were employed to build classical quantitative structure-activity relationship (QSAR) and three-dimensional QSAR models, respectively. The applicability domain (AD) of the classical QSAR model was assessed. Both the HM-BSM and CoMSIA approaches demonstrated good robustness, predictive ability, and mechanistic interpretability. The r2 and leave-one-out cross-validation squared correlated coefficient (q2LOO) values were 0.872 and 0.759 for the HM-BSM, and 0.976 and 0.751 for the CoMSIA model, respectively. The hPXR agonistic activity of the PFCs predicted by the built HM-BSM and CoMSIA agreed well with experimental activity, with root mean square error (RMSE) values of 0.0803 and 0.117, respectively, and external validation squared correlated coefficients (q2EXT) of 0.972 and 0.932, respectively. The hPXR agonistic activity of PFCs was related to their molecular polarizability, charge and atomic mass. Hydrogen bonding and hydrophobic interactions constituted the primary intermolecular forces between PFCs and the hPXR. The developed models were used to screen the PFCs with high hPXR agonistic activity.

2.
Mol Genet Genomic Med ; : e1023, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774634

RESUMO

BACKGROUND: The molecular and genetic mechanisms by which different single nucleotide variant alleles in specific genes, or at the same genetic locus, cause distinct disease phenotypes often remain unclear. Allelic truncating mutations of FBN1 could cause either classical Marfan syndrome (MFS) or a more complicated phenotype associated with Marfanoid-progeroid-lipodystrophy syndrome (MPLS). METHODS: We investigated a small cohort, encompassing two classical MFS and one MPLS subjects from China, whose clinical presentation included scoliosis potentially requiring surgical intervention. Targeted next generation sequencing was performed on all the participants. We analyzed the molecular diagnosis, clinical features, and the potential molecular mechanism involved in the MPLS subject in our cohort. RESULTS: We report a novel de novo FBN1 mutation for the first Chinese subject with MPLS, a more complicated fibrillinopathy, and two subjects with more classical MFS. We further predict that the MPLS truncating mutation, and others previously reported, is prone to escape the nonsense-mediated decay (NMD), while MFS mutations are predicted to be subjected to NMD. Also, the MPLS mutation occurs within the glucogenic hormone asprosin domain of FBN1. In vitro experiments showed that the single MPLS mutation p.Glu2759Cysfs*9 appears to perturb proper FBN1 protein aggregation as compared with the classical MFS mutation p.Tyr2596Thrfs*86. Both mutations appear to upregulate SMAD2 phosphorylation in vitro. CONCLUSION: We provide direct evidence that a dominant-negative interaction of FBN1 potentially explains the complex MPLS phenotypes through genetic and functional analysis. Our study expands the mutation spectrum of FBN1 and highlights the potential molecular mechanism for MPLS.

3.
Medicine (Baltimore) ; 98(48): e17830, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770199

RESUMO

RATIONALE: Neonatal scalp mass is common in clinical practice. After birth canal compression and traction force, a cephalohematoma is usually found. However, cephalohematoma with abscess is extremely rare and dangerous. So far, there have been no reported cases of multidrug-resistant Escherichia coli infections in giant neonatal scalp hematoma. PATIENT CONCERNS: We present a 9-day-old with a scalp abscess and a large scalp defect that remained after surgical drainage. DIAGNOSIS: Physical examination showed a giant mass suggestive in the parietal region. B-mode ultrasound indicated the scalp mass was liquid. The early diagnosis was massive scalp hematoma. During conservative treatment, purulent fluid flowed from the mass region through a rupture in the scalp. MR examination showed the scalp had burst and no abnormalities were found in the medial side of the skull and skull. INTERVENTIONS: The surgeon opened up the mass and removed necrotic tissue. The scalp was severely damaged; the aseptic auxiliary materials that we made in-house were used to gradually reduce the defect. OUTCOMES: The scalp was healed by anti-infection treatment and frequent changing of the dressings. The patient was successfully treated without two-stage surgery. There were no complications. LESSONS: A scalp hematoma is a potential site of infection. Anti-infection treatment and surgery are necessary to correct infected scalp hematoma. This work offers a new way of treating other large scalp defects.

4.
JAMA Oncol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750857
5.
Scand J Clin Lab Invest ; 79(8): 619-628, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710248

RESUMO

This study investigated the relationship between endothelial pyroptosis and the occurrence of systemic inflammatory response (SIR) after radiofrequency (RF) ablation of hepatic hemangiomas. Thirty-two patients with hepatic hemangiomas were treated with RF ablation and blood samples of the patients were collected at different time points. Immunohistochemistry staining was performed to evaluate the expression of caspase-1, gasdermin D (GSDMD), IL-1ß and IL-18 in hepatic hemangioma and subablated hemangioma tissue. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with sub-ablative hyperthermia with or without the addition of caspase-1 inhibitor, Ac-YVAD-CMK in the medium. Lactate dehydrogenase (LDH), IL-18, IL-1ß, caspase-1 and GSDMD were measured by enzyme-linked immunosorbent assay, real-time PCR and Western blot methods. An elevation of general SIR parameters (CRP and WBC), pyroptosis-related inflammatory cytokines (IL-1ß and IL-18) and LDH were observed 1-day post-RF ablation and their peak values were significantly correlated with ablated volume (p < .001) and ablation time (p < .001). Moreover, levels of pyroptosis-related inflammatory cytokines correlated well with general SIR parameters, respectively (p < .001). Immunohistochemical analysis showed the increased expression of caspase-1, GSDMD, IL-18 and IL-1ß in the endothelial cells of subablated hemangioma. In vitro experiments showed that subablative hyperthermia induced the caspase-1-associated endothelial pyroptosis and Ac-YVAD-CMK attenuated pyroptosis. In conclusion, SIR in patients treated by RF ablation for hepatic hemangiomas was significantly associated with the ablated volume and ablation time and endothelial pyroptosis may involve in the occurrence of SIR following RF ablation of hepatic hemangiomas.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31752653

RESUMO

Hymenoptera venom allergy is one of the common causes of anaphylaxis. However, when physicians make the diagnosis of Hymenoptera venom allergy, the histories of being stung are not always consistent with the results of venom specific IgE. With the development of component-resolved diagnosis, it is possible to accurately localize an allergic reaction to certain sensitized proteins. This paper reviewed the studies that have addressed the identified allergenicity and cross-reactivity of Hymenoptera venom allergens accepted by the WHO/IUIS Nomenclature Sub-committee, the component-resolved diagnosis of Hymenoptera venom allergy and its predictive values for the efficacy and safety of venom immunotherapy. Also, we paid special attention to the progress of Hymenoptera venom allergy in Asian countries.

7.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710424

RESUMO

BACKGROUND: EGFR mutational testing is crucial for advanced non-squamous NSCLC. PAP is a sensitive and selective method to detect rare mutations. METHODS: Eighty-five patients with non-squamous NSCLC were enrolled in this study. A set of paired plasma samples from each patient were collected and detected by PAP and ARMS. RESULTS: Of 85 paired samples, 78.8% (67/85) presented the same mutational status by the two methods. There was no statistically significant difference between the mutation frequencies in plasma samples detected with PAP and ARMS (p = 0.096). CONCLUSIONS: PAP technology appears to be an alternative choice with relatively high sensitivity for the detection of plasma EGFR mutations.

8.
Theranostics ; 9(24): 7251-7267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695766

RESUMO

In this study, we performed a comprehensively analysis of gene expression and DNA methylation data to establish diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC). Methods: We collected gene expression and DNA methylation datasets for over 1,200 clinical samples. Integrated analyses of RNA-sequencing and DNA methylation data were performed to identify DNA methylation-driven genes. These genes were utilized in univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to build a prognostic model. Recurrence and diagnostic models for HCC were also constructed using the same genes. Results: A total of 123 DNA methylation-driven genes were identified. Two of these genes (SPP1 and LCAT) were chosen to construct the prognostic model. The high-risk group showed a markedly unfavorable prognosis compared to the low-risk group in both training (HR = 2.81; P < 0.001) and validation (HR = 3.06; P < 0.001) datasets. Multivariate Cox regression analysis indicated the prognostic model to be an independent predictor of prognosis (P < 0.05). Also, the recurrence model successfully distinguished the HCC recurrence rate between the high-risk and low-risk groups in both training (HR = 2.22; P < 0.001) and validation (HR = 2; P < 0.01) datasets. The two diagnostic models provided high accuracy for distinguishing HCC from normal samples and dysplastic nodules in the training and validation datasets, respectively. Conclusions: We identified and validated prognostic, recurrence, and diagnostic models that were constructed using two DNA methylation-driven genes in HCC. The results obtained by integrating multidimensional genomic data offer novel research directions for HCC biomarkers and new possibilities for individualized treatment of patients with HCC.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31668370

RESUMO

Anti-angiogenic drugs are an effective therapeutic method for the treatment of melanomas. Apatinib is a small-molecule tyrosine kinase inhibitor, which has potent inhibitory activity on tumor angiogenesis. Due to the low water solubility and stability of Apatinib, we aimed to design and develop poly (lactic-co-glycolic acid) (PLGA) and Poloxamer 407 nanoparticles to encapsulate Apatinib (Apa/p NPs) to improve the efficacy of application in melanoma treatment. The size and morphology of the nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro proliferation assays were used to assess the capacity of Apa/p NPs to suppress the growth of B16 cells. Furthermore, we constructed melanoma models using C57BL/6 mice, and preliminary evaluation of the effect and mechanism of Apa/p NPs on tumor inhibition was performed in vivo. The results showed that the size of Apa/p NPs averaged 136 ±â€¯0.27 nm and the nanoparticles were evenly dispersed. Moreover, Apa/p NPs significantly inhibited the growth of B16 cells and melanoma tumors, compared with the naked drug treatment and control groups. The protein levels of VEGFR-2, phosphorylated (p)-VEGFR-2 and p-ERK1/2 in tumor tissues were inhibited by Apa/p NP treatment, as detected by Western blot. The results of this study suggested that Apa/p NPs could inhibit the growth of melanoma tumors by inhibiting the phosphorylation and expression of VEGFR-2 and downstream ERK1/2, providing a theoretical basis for the clinical application of Apatinib in the treatment of melanoma.

10.
Mol Cell Probes ; : 101479, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706013

RESUMO

AIMS: The study aimed to investigate the roles of miR-483-5p and IGF2 in osteoclast formation. METHODS: Blood and bone tissues were collected from osteoporosis and non-osteoporosis patients with hip fractures for gene expression analysis. CD14 + peripheral blood mononuclear cells (PBMCs) were isolated for differentiating osteoclasts. MiR-483-5p mimic and inhibitor was transfected into CD14 + PBMCs, respectively. Predicted by TargetScan and verified by Dual-luciferase reporter assay system, insulin-like growth factor-2 (IGF2) could be targeted by miR-483-5p. IGF2 expression vector was co-transfected with miR-483-5p mimic to study the role of IGF2 in miR-483-5p affecting osteoclast differentiation. Flow cytometry was performed for cell apoptosis analysis. RESULTS: High-expressed miR-483-5p and low-expressed IGF2 were frequently found in the serums and bone tissues derived from osteoporotic patients. We found that up-regulation of miR-483-5p in CD14 + PBMCs notably increased the number of TRAP-positive cells, at the same time, the expression levels of TRAP, nuclear factor of activated T-cells (NFATc1), cytoplasmic 1 (NFAT2) and Cathepsin K (CTSK) were also up-regulated. However, overexpressed IGF2 effectively reversed such effects produced by up-regulation of miR-483-5p on osteoclastogenesis-related factors in CD14 + PBMCs. Moreover, forced expression of IGF2 could also enhance apoptosis of osteoclasts reduced by miR-483-5p. CONCLUSIONS: Our study suggests that miRNA-483-5p is involved in the pathogenesis of osteoporosis by promoting osteoclast differentiation.

11.
Environ Pollut ; : 113433, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31761597

RESUMO

Epidemiology suggests ambient temperature is the triggers and potential activator of asthma. The role of high and low temperatures on airway inflammation of asthma, and the underlying molecular mechanism are not yet understood. A mouse model of asthma was adopted in our experiment. The BALB/c mice were exposed at different temperature for 4 h (2 h in the morning and 2 h in the afternoon) on weekday. The exposure temperatures were 10 °C, 24 °C and 40 °C. Ovalbumin (OVA) was used to sensitize the mice on days 14, 18, 22, 26, and 30, followed by an aerosol challenge for 30 min from day 32-38. After the final OVA challenge, lung function, serum protein and pulmonary inflammation were assessed. Comparing the OVA with the saline group at 24 °C, we saw a significant increase in: serum Total-IgE (p < 0.05); OVA-sIgE (p < 0.01); IL-4 (p < 0.05); IL-1ß (p < 0.01); IL-6 (p < 0.01); TNF-α (p < 0.01); and the ratio of IL-4/IFN-γ (p < 0.01). At the same time, there was a significant decrease in IFN-γ (p < 0.01). As the temperature increase, there is a U shape for immune proteins and pro-inflammatory factors with a peak value at 24 °C, exception for IFN-γ (inverted U-shape). After the high and low temperature exposure, the Ri and Re increased significantly, while Cldyn decreased significantly compared with the 24 °C group. Histopathological analysis of the OVA groups showed airway remodeling, airway wall thickening and deforming, and subepithelial fibrosis. More obvious changes were found in the high and low temperature exposure groups. The immunohistochemistry suggested that TRPs changed with temperatures. High and low temperatures can aggravate airway inflammation in a mouse model of asthma. TRPs play an important role in temperature aggravation of allergic asthma. The results suggest that asthmatics should avoid exposure to high and low temperatures for too long time.

12.
Phys Chem Chem Phys ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31728475

RESUMO

The boundary between a capacitor and a battery is vague for layered transition metal sulfides, especially when it comes to TiS2 with a multi-phase transition process. In this work we analyzed both the quasi-static process and dynamic process of K+ storage in TiS2 with carbonate based electrolytes, which proved to be an intercalation pseudocapacitive behavior.

13.
Opt Express ; 27(21): 29803-29816, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684237

RESUMO

Traditional methods for distortion measurement of large-aperture optical systems are time-consuming and ineffective because they require each field of view to be individually measured using a high-precision rotating platform. In this study, a new method that uses a phase diffractive beam splitter (DBS) is proposed to measure the distortion of optical systems, which has great potential application for the large-aperture optical system. The proposed method has a very high degree of accuracy and is extremely economical. A high-precision calibration method is proposed to measure the angular distribution of the DBS. The uncertainty analysis of the factors involved in the measurement process has been performed to highlight the low level of errors in the measurement methodology. Results show that high-precision measurements of the focal length and distortion were successfully achieved with high efficiency. The proposed method can be used for large-aperture wide-angle optical systems such as those used for aerial mapping applications.

14.
Injury ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31676073

RESUMO

INTRODUCTION: Treatment of comminuted patella fractures with tension band has resulted in impaired functional outcomes because the relationship between tension band and the tendons is always underestimated. We developed a modified enlacement (ME) technique to better place the tension-band under the quadriceps and patellar tendons and close to the patella. The study aimed to compare the ME with conventional enlacement (CE) technique regarding recovery of knee function. PATIENTS AND METHODS: 51 patients with comminuted patella fractures operated between January 2012 and December 2016 were reviewed retrospectively. 22 patients in the ME group (9 males and 13 females) with a mean age of 51.3 years, 29 patients in the CE group (16 males and 13 females) with a mean age of 47.1 years. ROM was measured at postoperative intervals of 1, 2, 4, 12, and 48 weeks; Knee function was evaluated using the Rasmussen scores at 4, 12, and 48 weeks postoperative. RESULTS: There was no difference (P = 0.082) regarding the fracture healing time between the two groups. Patients with the ME technique had clinically and statistically significantly higher ROM recovery throughout the study period (P < 0.001) with an earlier recovery. The Rasmussen scores also demonstrated significant improvements in patients with ME technique than CE group at all time-points (P < 0.05). Three patients in the CE group had migration of K-wires, with no migration observed in the ME group. CONCLUSION: The ME technique enables improved clinical outcomes and functional performance for the treatment of comminuted patella fractures.

15.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691337

RESUMO

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and single-nucleotide polymorphisms (SNPs) in certain genes influence risk of ALL. Although FOXO3 had been demonstrated to be involved leukemia, the role of FOXO3 polymorphisms was still not clear. In the present study, we explored the association of FOXO3 SNPs with ALL risk in Chinese children. We genotyped four polymorphisms (rs17069665 A>G, rs4945816 T>C, rs4946936 C>T, and rs9400241 A>C) of FOXO3 in 425 ALL cases and 1339 health controls. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Further analyses were performed to explore associations of rs17069665 and rs9400241 with ALL susceptibility in terms of age, gender, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. We found rs17069665 related to the increased ALL risk (OR = 1.76; 95% CI = 1.02-3.04), rs9400241 related to decreased ALL risk (OR = 0.80; 95% CI = 0.64-0.99). The effects of rs17069665 on ALL risk were more predominant in males and children < 10 years, and patients with lower rates of platelet or neutrophil. As for rs9400241, the effects were more predominant in children < 10 years, and in patients with pre B ALL, positive MRD, anemia, or hepatomegaly. In conclusion, FOXO3 gene polymorphisms influence the risk of ALL in children and might be a potential biomarker for ALL susceptibility.

16.
Int J Occup Saf Ergon ; : 1-37, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31736413

RESUMO

Recently, the significance of organizational support and commitment in workplace safety has gained much recognition. The improvement of individual safety behavior needs more convincing and effective evidence. This study constructed a comprehensive theoretical model and used meta-analysis to examine the relationships between perceived organizational support for safety (POSS), organizational commitment (OC) and employee safety behavior (SB). Support was found for the study's hypothesis that both perceived organizational support for safety and organizational commitment had a positive association with employee safety behavior, with the latter demonstrating the stronger relationship. However, organizational commitment was not mediated by perceived organizational support for safety and employee safety behavior. Results show that in general industries and developed regions, employees' safety behavior are more vulnerable to perceived organizational support for safety and organizational commitment than those in high-risk industries and developing regions. The implications of the findings and suggestions for further research are discussed.

17.
Ecotoxicol Environ Saf ; 185: 109698, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31574370

RESUMO

Salt-tolerant rice cultivar (sea rice) is a research hotspot worldwide due to its high yield in high salinity soil. However, knowledge regarding the cadmium (Cd) effects on the growth of sea rice is limited. To determine the short-term and long-term impact of Cd stress, relatively low/high Cd-accumulative rice cultivars and sea rice were grown to compare their growth responses to Cd stress over time. The results showed that sea rice presented the highest Cd concentrations in the root, stem, and leaves under 32-days of Cd stress. Cd stress shortened and thickened the rice root, and decreased the proportion of root diameters in the 0-0.2 mm range. Cd stress remarkably increased the Cd and Fe concentration in dithionite-citrate-bicarbonate (DCB) extracts, and the DCB-Cd and DCB-Fe concentrations were the highest in sea rice. The subcellular distribution of Cd in the rice roots indicated that Cd accumulated the most in the soluble fraction and cell wall. The contents of pectin and hemicellulose 2 in the root cell wall of the low-Cd accumulative rice variety CL755 were higher than those in MXZ and sea rice. Collectively, this work provides a general understanding of the Cd effects on sea rice growth and indicates that sea rice has a relatively high Cd accumulation compared with the other two rice cultivars. However, the specifically-related mechanism remains to be further studied.

19.
J Biol Chem ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628189

RESUMO

A highly specialized cytoskeletal protein keratin 75 (K75), expressed primarily in hair follicles, nail beds and lingual papillae, was recently discovered in dental enamel - the most highly mineralized hard tissue in the human body. Among many questions this discovery poses, the fundamental question regarding the trafficking and secretion of this protein, lacking a signal peptide, is of an utmost importance. Here we present evidence that K75 is expressed during the secretory stage of enamel formation and is present in the forming enamel matrix. We further show that K75 is secreted together with major enamel matrix proteins amelogenin and ameloblastin and it was detected in Golgi and the ER-Golgi intermediate compartment (ERGIC) but not in rER. Inhibition of ER-Golgi transport by brefeldin A did not affect the association of K75 with Golgi, while ameloblastin accumulated in rER and its transport from rER into Golgi was disrupted. Together these results indicate that K75, a cytosolic protein lacking signal sequence, is secreted into the forming enamel matrix utilizing portions of conventional ER-Golgi secretory pathway. To the best of our knowledge, this is the first study providing insights into mechanisms of keratin secretion.

20.
J Cell Mol Med ; 23(12): 8173-8183, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31625681

RESUMO

Dexmedetomidine (Dex) has been proven to exert protective effects on multiple organs in response to ischaemia-reperfusion injury, but the specific mechanism by which this occurs has not been fully elucidated. The purpose of this study was to investigate whether Dex attenuates spinal cord ischaemia-reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS). Our team established a model of SCIRI and utilized the endoplasmic reticulum agonist thapsigargin. Dex (25 g/kg) was intraperitoneally injected 30 minutes before spinal cord ischaemia. After 45 minutes of ischaemia, the spinal cord was reperfused for 24 hours. To evaluate the neuroprotective effect of Dex on SCIRI, neurological function scores were assessed in rats and apoptosis of spinal cord cells was determined by TUNEL staining. To determine whether the endoplasmic reticulum apoptosis pathway CNPY2-PERK was involved in the neuroprotective mechanism of Dex, the expression levels of related proteins (CNPY2, GRP78, PERK, CHOP, caspase-12, caspase-9 and caspase-3) were detected by western blot analysis and RT-PCR. We observed that Dex significantly increased the neurological function scores after SCIRI and decreased apoptosis of spinal cord cells. The expression of ERS-related apoptosis proteins was significantly increased by SCIRI but was significantly decreased in response to Dex administration. Taken together, the results of this study indicate that Dex may attenuate SCIRI by inhibiting the CNPY2-ERS apoptotic pathway.

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