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1.
Sci Total Environ ; 712: 135631, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050395

RESUMO

Total petroleum hydrocarbons (TPH) in activated petroleum waste sludge (PWS) hindered the disintegration of sludge, and microbubble ozonation (MB-O3) was explored to separate the TPH and solids particle, enhance the decomposition of PWS, and improve the efficiency of ozonation. The maximum solubilization of PWS reached to approximately 41.9% at an ozone dose of 5.40 gO3/gTS, two times higher than the control one. The ozone mass transfer coefficient of kLa increased from 0.1101 min-1 to 0.2293 min-1 in MB-O3, resulting in the formation of a higher concentration of 1.29 µg/L hydroxyl radicals. The medium diameter sharply declined from 38.6 µm to 17.5 µm, and more porous surface of sludge flocs was observed, indicating that MB-O3 destroyed the water-oil-gel structure and contributed to the stripping of TPH. The soluble chemical oxygen demand was released by 390% with respect to initial value (from 764 to 3740 mg/L) and acetic acid was the predominant component with yield of 590 ± 7.1 mg/L, which could be served as an additional carbon source. This study provides an efficient approach to achieve sludge disposal and simultaneous enhance the stripping of total petroleum hydrocarbons from oil refinery sludge.

2.
J Diabetes ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919985

RESUMO

BACKGROUND: This study aims to estimate type 2 diabetes mellitus (T2DM) incidence with DNA methylation of the thioredoxin-interacting protein (TXNIP) gene and its interaction with environmental factors. MATERIALS AND METHODS: This case-control study included 286 incident T2DM cases and 286 non-T2DM controls matched by sex, age, marital status, race, and residence village nested in the Rural Chinese Cohort Study. A conditional logistic regression model was used to estimate the association of DNA methylation at TXNIP gene with T2DM risk. Also, multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to investigate the interaction between TXNIP methylation and environmental risk factors. RESULTS: Methylation levels of all five CpG loci at TXNIP gene were significantly lower in T2DM than in controls (all P < .001). With increasing methylation level, risk of T2DM was significantly decreased (odds ratio, 95% CI 0.80, 0.69-0.94 for CpG1; 0.80, 0.69-0.93 for CpG2; 0.70, 0.56-0.88 for CpG3; 0.78, 0.66-0.92 for CpG4; and 0.76, 0.60-0.97 for CpG5). Additionally, the essential interactions among TXNIP methylation, obesity, and hypertriglyceridemia were identified by CART and MDR analyses. On logistic regression analysis, the risk of T2DM was reduced with terminal node 5 (CpG3 methylation ≥72%, nonobesity, normal triglyceride (TG) level, and CpG4 methylation ≥83%) vs terminal node 1 (CpG3 methylation <72%) (odds ratio 95% CI 0.20, 0.10-0.40). CONCLUSIONS: TXNIP methylation is associated with T2DM incidence in a Chinese population. Interaction between TXNIP methylation and environmental factors may influence T2DM risk and needs more investigation. HIGHLIGHTS: This is the first prospective nested case-control study in rural Chinese people to estimate the association of the methylation level of the thioredoxin-interacting protein (TXNIP) gene and its interaction with type 2 diabetes mellitus (T2DM) risk. We found a significant negative association between the methylation level of TXNIP gene and T2DM incidence. Interaction among TXNIP gene hypomethylation, obesity, and hypertriglyceridemia increased the risk of T2DM.

3.
Chemosphere ; 243: 125354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31759208

RESUMO

Dissolved organic matter (DOM) is a critical component of high-strength organic wastewater, and the study of them from molecular perspective could improve the removal efficiency. Leachate samples were collected from China's largest two stage anaerobic/aerobic membrane bioreactor and nanofiltration (A/O-MBR-NF) process, with the treatment capacity of 5000 t/d, and characterized by electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) from molecular perspective. High molecular weight (m/z > 500) compounds with 40-50 carbon atoms and 15-20 double bond equivalence (DBE) were biodegraded into medium molecular weight compounds with 10-20 carbon atoms and ∼10 DBE. Contribution of lipids and unsaturated hydrocarbons compounds in DOM turned into 42.1% and 2.5%, respectively, while contribution of condensed aromatics in DOM dramatically increased to 15.4% in leachates along the A/O-MBR process. Most of DOM was converted into higher polymerization degree and accumulated in concentrated leachate (CL). Sulfur-containing compounds, whose relative peak ratio accounted for 56.4%, were regarded as recalcitrant DOM in CL. Increase of retention time in anaerobic unit for raw leachate might be useful for decomposing the long-chain organic compounds, which could also reduce loadings for the following A/O-MBR process. Well-focus techniques such as sulfur-oxidation bacteria could be introduced into the MBR unit for better removing organo-sulfur compounds. Advanced oxidation processes for CL degradation would be efficiency for the removal of recalcitrant DOM. Thus, leachate could be disposed in a zero-discharge way based on the practical experience of such a typical working treatment process.

4.
J Hazard Mater ; 384: 120912, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31640936

RESUMO

Odor nuisance related to municipal solid waste (MSW) disposal is one of the main incentives to counter the Not-In-My-Backyard Syndrome. Moreover, integrated odor management contributes to specific odor control at different waste treatment stages. In this study, odor emissions along typical MSW streams were categorized based on their olfactive and environmental impacts after a field investigation of the residential district (RD), transfer station (TS), and landfill (LF) in the Chongming Eco-island. It was found that odorants, especially NH3 and sulfides, increased along the MSW stream, with total chemical concentration increasing from 1241.5 ± 235.6 to 6947.2 ± 1726.8 µg/m3. Source separation and co-landfill system, which premixes the MSW with bottom ash (BA) at a ratio of 5:1, were speculated to efficiently attenuate odorants. Sulfides reduced owing to an increase in trace metal dissolution and carbon source consumption with the addition of BA at the LF, whereas NH3 in the leachate pond increased due to enhanced biodegradation and alkalinity. Photochemical ozone formation (6.7 × 10-8-8.6 × 10-5 personal equivalent, PE), nutrient enrichment (5.4 × 10-8-4.6 × 10-5 PE), and acidification (4.8 × 10-8-4.1 × 10-5 PE) were the major environmental impact categories. The priority odor pollutants screened using ternary fuzzy synthetic system could reflect the impact of olfaction and environment and greatly varied along the waste stream.

5.
J Drug Target ; 28(2): 142-153, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31305176

RESUMO

Polydopamine (PDA), a dopamine-derived endogenous catecholamine polymer, has recently attracted considerable interest as photothermal reagent, particularly interesting in the application of multimodal synergistic cancer therapeutics. For surface-mediated drug delivery, PDA-based platforms exhibited excellent stability, biocompatibility and photothermal performance under the near infra-red (NIR) irradiation. Unfortunately, it was limited by concerns about non-selectivity, lower anticancer efficiency and potential cytotoxicity. Therefore, numbers of literatures have been reported on various modified PDA to improve targeting ability, reduce toxicity and combine with multiple treatment modes. Here, the purpose of this review is to summarise these contemporary PDA-based novel designs including physical, chemical as well as biological for potential strategies in the cancer target treatment according to their various stimuli-responsive properties, such as formulation types, pH, glutathione (GSH), peptides and receptors. In addition, we also discussed the structural properties and possible synthesis mechanisms of PDA in general which may provide an understanding of these current approaches and hope to explore the potential applications for future improvements about PDA.

6.
Dig Dis Sci ; 65(1): 329-335, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332625

RESUMO

BACKGROUND: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux. AIMS: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL. METHODS: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated. RESULTS: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients. CONCLUSIONS: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients.

7.
Prostate ; 80(3): 256-266, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31856338

RESUMO

BACKGROUND: Because androgen receptor (AR) signaling is essential for prostate cancer (PCa) initiation and progression, castration is the main approach for treatment. Unfortunately, patients tend to enter a stage called castration-resistant prostate cancer (CRPC) despite the initial response to castration. For various reasons, AR signaling is reactivated in CRPC. As such, AR signaling inhibitors, such as enzalutamide, has been approved by the Food and Drug Administration to treat CRPC in the clinic. However, the limited success of these new drugs suggests an immediate unmet need to understand the underlying mechanisms for resistance so novel targets can be identified to enhance their efficacy. METHODS: An unbiased bioinformatics analysis was performed with the existing human patient dataset and RNA-seq results of in-house PCa cell lines to identify new targets to overcome enzalutamide resistance. Cell viability and growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and colony formation assay. Cell invasion and migration were detected by transwell assay. Protein levels were detected by Western blot or immunofluorescence. RESULTS: We found that the noncanonical Wnt signaling was activated in enzalutamide-resistant PCa cells and that the activation of noncanonical Wnt signaling was correlated with AR expression and disease progression. This was validated by the elevated expression of noncanonical Wnt pathway members such as Wnt5a, RhoA, and ROCK in enzalutamide-resistant PCa cells in comparison to their enzalutamide-sensitive counterparts. And, both Y27632, an inhibitor of ROCK, and depletion of ROCK enhanced the efficacy of enzalutamide in enzalutamide-resistant PCa cells. Of significance, a combination of Y27632 and enzalutamide inhibited 22RV1-derived xenograft tumor growth synergistically. Finally, ROCK depletion plus enzalutamide treatment inhibited invasion and migration of enzalutamide-resistant PCa cells via inhibition of epithelial-mesenchymal transition. CONCLUSIONS: The noncanonical Wnt pathway is activated in enzalutamide-resistant PCa and inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance and enhances its efficacy in CRPC.

8.
Nat Mater ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873228

RESUMO

Nature has evolved strategies to encode information within a single biopolymer to program biomolecular interactions with characteristic stoichiometry, orthogonality and reconfigurability. Nevertheless, synthetic approaches for programming molecular reactions or assembly generally rely on the use of multiple polymer chains (for example, patchy particles). Here we demonstrate a method for patterning colloidal gold nanoparticles with valence bond analogues using single-stranded DNA encoders containing polyadenine (polyA). By programming the order, length and sequence of each encoder with alternating polyA/non-polyA domains, we synthesize programmable atom-like nanoparticles (PANs) with n-valence that can be used to assemble a spectrum of low-coordination colloidal molecules with different composition, size, chirality and linearity. Moreover, by exploiting the reconfigurability of PANs, we demonstrate dynamic colloidal bond-breaking and bond-formation reactions, structural rearrangement and even the implementation of Boolean logic operations. This approach may be useful for generating responsive functional materials for distinct technological applications.

9.
Opt Express ; 27(24): 35700-35709, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878737

RESUMO

This paper proposes a distributed collaborative learning approach for cognitive and autonomous multi-domain elastic optical networking (EON). The proposed approach exploits a knowledge-defined networking framework which leverages a broker plane to coordinate the operations of multiple EON domains and applies machine learning (ML) to support autonomous and cognitive inter-domain service provisioning. By employing multiple distributed ML blocks learning domain-level features and working with broker plane aggregation ML blocks (through the chain rule-based training), the proposed approach enables to develop cognitive networking applications that can fully exploit the multi-domain EON states while obviating the need for the raw and confidential intra-domain data. In particular, we investigate end-to-end quality-of-transmission estimation application using the distributed learning approach and propose three estimator designs incorporating the concepts of multi-task learning (MTL) and transfer learning (TL). Evaluations with experimental data demonstrate that the proposed designs can achieve estimation accuracies very close to (with differences less than 0.5%) or even higher than (with MTL/TL) those of the baseline models assuming full domain visibility.

10.
J Diabetes ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642584

RESUMO

BACKGROUND: To study the association between anthropometric measurements and the risk of diabetes and impaired fasting glucose (IFG) and compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to determine the best indicator and its optimal cutoffs for predicting type 2 diabetes and IFG. METHODS: A Chinese prospective (2011-2019) cohort named the Jingchang cohort that included 48 001 participants was studied. Using Cox proportional hazard models, hazard ratios (HRs) for incident type 2 diabetes or IFG per 1 SD change in BMI, WC, and WHtR were calculated. Area under the curve (AUC) was compared to identify the best anthropometric variable and its optimal cutoff for predicting diabetes. RESULTS: The association of BMI, WC,0 and WHtR with type 2 diabetes or IFG risk was positive in the univariate and multivariable-adjusted Cox proportional hazard models. Of all three indexes, the AUC of BMI was largest and that of WC was smallest. The derived cutoff values for BMI, WC, and WHtR were 24.6 kg/m2 , 89.5 cm, and 0.52 in men and 23.4 kg/m2 , 76.5 cm, and 0.47 in women for predicting diabetes, respectively. The derived cutoff values for BMI, WC, and WHtR were 23.4 kg/m2 , 87.5 cm, and 0.50 in men and 22.5 kg/m2 , 76.5 cm, and 0.47 in women for predicting IFG, respectively. CONCLUSIONS: Our derived cutoff points were lower than the values specified in the most current Asian diabetes guidelines. We recommend a cutoff point for BMI in Asians of 23 kg/m2 and for WC a cutoff point of 89 cm in men and 77 cm in women to define high-risk groups for type 2 diabetes; screening should be considered for these populations. HIGHLIGHTS: We observed significant and positive associations of the risk of type 2 diabetes with BMI, WC and WHtR, and we identified BMI as the best obesity predictor for diabetes. Our derived cutoff points were lower than the values specified in the most current Asian diabetes guidelines, and we recommend a cutoff point for BMI in Asians of 23 kg/m2 and a cutoff point for WC of 89 cm in men and 77 cm in women to define high-risk groups for type 2 diabetes; screening should be considered for these populations.

11.
Nanoscale ; 11(42): 19772-19782, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31408078

RESUMO

Micro-supercapacitors (MSCs) with thick interdigital microelectrodes of carbon-based materials exhibit excellent electrochemical performance and hold tremendous promise for applications in microscale energy storage devices. Here, a scalable strategy to fabricate thick embedded multiwalled carbon nanotubes (MWCNTs) as interdigital microelectrodes for MSCs has been developed and investigated. To this end, sufficient MWNCT inks are firstly cast onto pre-patterned microcavity surfaces and then more MWCNT materials are embedded into the microcavities by rapid solvent evaporation. After removal of residual materials from the surfaces by a doctor-blading process, thick interdigital MWCNT microelectrodes with heights up to 190 µm are obtained. These embedded microelectrodes simplify the device structure and improve the mechanical flexibility by acting as both active materials and current collectors. Using interdigital microelectrodes with a width of 250 µm and an interspace of 50 µm, the fabricated MSCs exhibit outstanding electrochemical performance with a high capacitance of 19.5 mF cm-2 and an energy density of 2.48 µW h cm-2 at a power density of 24.7 µW cm-2. On the other hand, four light emitting diodes (LEDs) are successfully powered by three series of MSCs, indicating that MSCs can be connected in series and parallel to yield suitable operating voltages and currents for practical applications.

12.
Front Oncol ; 9: 523, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293967

RESUMO

Non-muscle invasive bladder cancer (NMIBC) patients often have fewer treatment options, and suffer the progression of disease due to mechanisms that are not clear, as well as due to its diversity. This study was designed to explore the molecular mechanism of bladder cancer through an RNA-seq. In addition to conventional analyses, we also simplified the network through modularization using the WGCNA algorithm, with the help of the topological overlapping matrix and hierarchical cluster tree, which are based on the PPI network of STRING. Furthermore, the hub genes were confirmed through survival analyses in the independent cohorts (n = 431). Among them, 15 genes were significantly associated with poor prognosis. Finally, we validated the results at mRNA and protein level using qRT-PCR, IHC and western blotting. Taken together, our research is important for the prediction, as well as the prospective clinical development of drug targets and biomarkers.

13.
J Biol Chem ; 294(25): 9911-9923, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31085587

RESUMO

Enzalutamide, approved by the United States Food and Drug Administration in 2018 for the management of metastatic castration-resistant prostate cancer (CRPC), is an androgen receptor (AR) inhibitor. It blocks androgen binding to the AR, AR nuclear translocation, and AR-mediated DNA binding. Unfortunately, a considerable proportion of tumors eventually develop resistance during the treatment. The molecular mechanisms underlying enzalutamide resistance are not completely understood. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressor complex 2, has been proposed as a prognostic marker for prostate cancer (PCa). With the goal to test whether EZH2 also plays a critical role in acquisition of enzalutamide resistance in CRPC, here we examined whether EZH2 inhibition/depletion enhances the efficacy of enzalutamide in enzalutamide-resistant PCa cells. We show that combining the EZH2 inhibitor GSK126 with enzalutamide synergistically inhibits cell proliferation and colony formation and promotes apoptosis in enzalutamide-resistant PCa cells. EZH2 depletion also overcomes enzalutamide resistance in both cultured cells and xenograft tumors. Mechanistically, we found that EZH2 directly binds to the promoter of prostate-specific antigen and inhibits its expression in enzalutamide-resistant PCa cells. In agreement, bioinformatics analysis of clinical RNA sequencing data involving GSEA indicated a strong correlation between AR and EZH2 gene expression during PCa progression. Our study provides critical insights into the mechanisms underlying enzalutamide resistance, which may offer new approaches to enhance the efficacy of enzalutamide in CRPC.

14.
ACS Appl Mater Interfaces ; 11(19): 17796-17803, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31007008

RESUMO

Sensitivity of the sensor is of great importance in practical applications of wearable electronics or smart robotics. In the present study, a capacitive sensor enhanced by a tilted micropillar array-structured dielectric layer is developed. Because the tilted micropillars undergo bending deformation rather than compression deformation, the distance between the electrodes is easier to change, even discarding the contribution of the air gap at the interface of the structured dielectric layer and the electrode, thus resulting in high pressure sensitivity (0.42 kPa-1) and very small detection limit (1 Pa). In addition, eliminating the presence of uncertain air gap, the dielectric layer is strongly bonded with the electrode, which makes the structure robust and endows the sensor with high stability and reliable capacitance response. These characteristics allow the device to remain in normal use without the need for repair or replacement despite mechanical damage. Moreover, the proposed sensor can be tailored to any size and shape, which is further demonstrated in wearable application. This work provides a new strategy for sensors that are required to be sensitive and reliable in actual applications.

15.
J Int Med Res ; 47(6): 2413-2423, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991874

RESUMO

OBJECTIVE: To compare modified expansive laminoplasty and fusion (MELF) with anterior cervical corpectomy and fusion (ACCF), and anterior cervical discectomy and fusion (ACDF), in treating four-level cervical spondylotic myelopathy (CSM). METHODS: This retrospective study included patients with four-level CSM who had undergone surgery at the Affiliated Hospital of Qingdao University between January 2013 and May 2015. D-values, Cobb's angle, Japanese Orthopaedic Association (JOA) score and quality of life (SF-36 scores) were compared between patients treated with ACCF/ACDF versus MELF. RESULTS: Twenty-six patients who underwent ACCF/ACDF and 26 who underwent MELF were included, and all showed bone fusion following treatment. The most common complications were dysphasia (12/26) in the ACCF/ACDF group and axial neck pain (7/26) in the MELF group. C5 nerve root palsy was not observed in either group. D value and Cobb's angle changes showed that ACDF/ACCF was more effective in curve correction than MELF. Postoperative improvements in JOA and SF-36 scores were noted in both groups, with no statistically significant between-group differences. CONCLUSION: Anterior and posterior approaches may produce similar clinical outcomes in the surgical management of four-level CSM. MELF may avoid known complications of the posterior approach.


Assuntos
Vértebras Cervicais/cirurgia , Laminoplastia/métodos , Complicações Pós-Operatórias , Doenças da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Espondilose/cirurgia , Idoso , Vértebras Cervicais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/patologia , Espondilose/patologia , Resultado do Tratamento
16.
Phytother Res ; 33(7): 1794-1804, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30993793

RESUMO

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra-zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC50 is around 150 µg/ml for human pancreatic ASPC-1 and human colon HT-29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC-1 cancer cells and human colon HT-29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT-29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC-induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Syzygium , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo
17.
Orthop Traumatol Surg Res ; 105(3): 557-562, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30935813

RESUMO

INTRODUCTION: Management of minimally displaced lateral humeral condyle fractures in pediatric patients is controversial. This is primarily because with current imaging modalities it is difficult to accurately and conveniently determine the stability of the fractures by detecting the integrity of the cartilage hinge. Nevertheless, transverse ultrasonography has not been intensively reported in previous studies. HYPOTHESIS: Transverse ultrasonography can determine the integrity of the cartilage hinge in minimally displaced lateral condyle fractures. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 39 pediatric patients with minimally displaced fractures of the lateral humeral condyle who underwent transverse ultrasonography between 2014 and 2017. Conservative treatment was given to pediatric patients with intact cartilage hinges that had been confirmed by transverse ultrasound images. Surgical treatment was recommended for pediatric patients with disrupted cartilage hinges. Data regarding healing of the lateral humeral condyle fractures were recorded and analyzed. RESULTS: According to transverse ultrasonography, there were 14 children with intact cartilage hinges and 25 children with disrupted cartilage hinges. Fourteen children with intact cartilage hinges of the fracture were treated conservatively, and none of them showed secondary displacement. There were 16 children in whom there was surgical intervention, and 9 other children decided to have conservative treatment among the 25 children with disruption of the cartilage hinge. Five of these 9 children who underwent conservative treatment were found to have further displacement during an average of 12.6 days after the fracture event, and no other patient was found to have further displacement. CONCLUSION: Transverse ultrasonography can simply and accurately determine the stability of minimally displaced lateral condyle fractures without sedation, ionizing radiation or invasive techniques. We recommend routine use of transverse ultrasonography to detect stability of the fractures, which can effectively avoid inadequate treatment and unnecessary surgery in pediatric patients with minimally displaced fractures of the lateral humeral condyle. LEVEL OF EVIDENCE: IV, retrospective cohort study.

18.
Int J Biol Sci ; 15(3): 617-627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745848

RESUMO

Metformin, a common therapeutics for type 2 diabetics, was recently demonstrated to possess antitumor activity in various cancer types. However, its therapy effect in renal cell carcinoma (RCC) still remains controversial. In this study, we found that metformin treatment in RCC cells lead to activation of AMPK, which suppressed the cell proliferation under normal condition, but enhanced cell proliferation under glucose deprivation (GD) condition. Depletion of AMPK by siRNA abolished the proliferation effect of MF under GD condition. Mechanistic investigations revealed that the effect of AMPK on cell proliferation under GD condition is dependent on its nuclear translocation. Moreover, the nuclear AMPK recruits PKM2 and ß-Catenin to form a complex, which promotes the transcription of cell proliferation related genes, including CCND1 and c-Myc. Furthermore, depletion of PKM2 or ß-Catenin abrogated the proliferative effects of metformin under GD condition. And inhibition of PKM2 also re-sensitized the A498 xenograft in response to metformin treatment. Together, our results suggested that combined of AMPK activation and PKM2 depletion or inhibition can achieve better therapeutic effect for RCC patients.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Membrana/metabolismo , Metformina/farmacologia , Hormônios Tireóideos/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
19.
Cancer Sci ; 110(4): 1220-1231, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30719823

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The most important reason for the occurrence of HCC is hepatitis C or B infection. Moreover, genetic factors play an important role in the tumorigenesis of HCC. Here, we demonstrated that Krüppel-like factor 2 (KLF2) expression was downregulated in HCC samples compared with adjacent tissues. Additionally, KLF2 was shown to inhibit the growth, migration and colony-formation ability of liver cancer cells. Further mechanistic studies revealed that KLF2 can compete with Gli1 for interaction with HDAC1 and restrains Hedgehog signal activation. Together, our results suggest that KLF2 has potential as a diagnostic biomarker and therapeutic target for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transformação Celular Neoplásica/metabolismo , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Genes Reporter , Humanos , Masculino , Camundongos , Camundongos Knockout , Proteína GLI1 em Dedos de Zinco/metabolismo
20.
J Cell Biochem ; 120(1): 243-252, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30216500

RESUMO

Chemotherapy drug resistance frequently happens in more than 50% of bladder cancer patients and is the major obstacle for the bladder cancer therapy. Recent studies have shown that long noncoding RNA (lncRNA) is involved in the development of chemoresistance. In this study, we reported hypoxia inducible factor 1α-antisense RNA 2 (HIF1A-AS2), as a subtype-specific hypoxia inducible lncRNA, is upregulated in bladder cancer cells and tissue after cisplatin (Cis) treatment. The induction of HIF1A-AS2 in bladder cancer cells rendered resistance to Cis-induced apoptosis. Silencing HIF1A-AS2 in Cis-resistant bladder cancer cells was re-sensitized to Cis-induced apoptosis. Mechanically, we found that HIF1A-AS2 suppressed the transcription activity of p53 family proteins by promoting the expression of high-mobility group A1 (HMGA1). The induction of HMGA1 physically interacts with p53, p63, and p73, and therefore constrains their transcriptional activity on Bax. Knockdown of HIF1A-AS2 or HMGA1 rescued the expression of Bax, which therefore enhanced the killing effect of Cis. Furthermore, we also found that the expression of HIF1A-AS2 was higher in the human bladder tumor tissues after Cis treatment, and was positive correlated to the expression of HIF1α and HMGA1. This study suggests that upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway to promote Cis resistance in bladder cancer. Our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer.


Assuntos
Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Proteína HMGA1a/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Transcrição Genética , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Neoplasias da Bexiga Urinária/patologia , Proteína X Associada a bcl-2/metabolismo
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