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1.
J Endocrinol ; 244(1): 223-236, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31648186

RESUMO

Obesity is a worldwide health problem. Semaphorins are involved in axonal guidance; however, the role of secretory semaphorin 3G (SEMA3G) in regulating adipocyte differentiation remains unclear. Microarray analysis showed that the SEMA3G gene was upregulated in an in vitro model of adipogenesis. In this study, SEMA3G was highly expressed in the white adipose tissue and liver. Analysis of 3T3-L1 cell and primary mouse preadipocyte differentiation showed that SEMA3G mRNA and protein levels were increased during the middle stage of cell development. In vitro experiments also showed that adipocyte differentiation was promoted by SEMA3G; however, SEMA3G inhibition using a recombinant lentiviral vector expressing a specific shRNA showed the opposite results. Mice were fed a chow or high-fat diet (HFD); knockdown of SEMA3G was found to inhibit weight gain, reduce fat mass in the tissues, prevent lipogenesis in the liver tissue, reduce insulin resistance and ameliorate glucose tolerance in HFD mice. Additionally, the effect of SEMA3G on HFD-induced obesity was activated through PI3K/Akt/GSK3ß signaling in the adipose tissue and the AMPK/SREBP-1c pathway in the liver. Moreover, the plasma concentrations of SEMA3G and leptin were measured in 20 obese and 20 non-obese human subjects. Both proteins were increased in obese subjects, who also exhibited a lower level of adiponectin and presented with insulin resistance. In summary, we demonstrated that SEMA3G is an adipokine essential for adipogenesis, lipogenesis, and insulin resistance and is associated with obesity. SEMA3G inhibition may, therefore, be useful for treating diet-induced obesity and its complications.

2.
J Phys Condens Matter ; 32(7): 075401, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31627192

RESUMO

The superconducting behavior in IVB-VB group transition metal nitrides and carbides has generally been associated with the phonon anomaly and Fermi surface nesting. However, the origin of phonon anomaly has remained ambiguous (i.e. longitudinal acoustic or transverse acoustic modes). We performed first-principles calculations to investigate the phononic properties of these materials and theoretically confirmed that the Kohn anomaly originates from the lower transverse acoustic mode along the ГX direction, thereby revealing the frequency derivative discontinuity of the mode. In particular, the Kohn anomaly region is found to move from the interior to the boundary X point of the Brillouin zone with increasing number of valence electrons. We deduced that the Kohn anomaly originated from the electrons of the filled energy level near the van Hove singularity. These results suggest that the screening of the ionic electric field decreases, while the coupling of conduction electrons with the highly degenerate modes between the TA∥ and LA via Umklapp scattering process increases. The Fermi surface nesting also plays a role in enhancing the superconductivity. The electronic excitation effect induces a stabilization of the V2 group transition metal nitrides.

3.
J Hazard Mater ; 383: 121160, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31518812

RESUMO

The application of current soil quality standards based on total arsenic (As) fails to assess the ecological risks of soil arsenic or to ensure the safety of crops and foods. In this study, bioavailable arsenic instead of total arsenic was applied to improve predictive models for arsenic transfer from soil to wheat (Triticum turgidum L.). The stepwise multiple-linear regression analysis showed that bioavailable arsenic and amorphous iron oxides (FeOX) were the two most important factors contributing to arsenic accumulation in wheat grain, with the explained percentage of variation being up to 82%. Compared with the bioavailable arsenic extracted by NH4H2PO4, bioavailable arsenic extracted by HNO3 from soils generated better predictions of the amount of arsenic in grain. The best reliable model was log[Asgrain] = 0.917 log[HNO3-As] - 0.452 log[FeOX] - 1.507 (R2 = 0.82, P <  0.001). Consistently, bioavailable arsenic and FeOX were also the key factors to predict arsenic accumulation in wheat straw, leaves and spikes. Our prediction models was successfully verified for three independent soils. Our results highlight the role of soil bioavailable heavy metals in predicting their transfer in soil-plant systems and can be used to improve existing Chinese soil quality standards.

4.
Chemosphere ; 239: 124737, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493755

RESUMO

Antibiotics are of concern due to their prevalent detection in aquatic environment. Sulfate radical based advanced oxidation processes show a great capacity to degrade antibiotics, but the mechanisms are still unclear. In this work, the degradation mechanism of fluoroquinolones (FQs), a major group of antibiotics, in UV/Fe2+/PMS was deeply investigated. The degradation process was in-situ and real-time monitoring by illumination-assisted droplet spray ionization mass spectrometry. A series of reactive intermediates were captured, and further characterized by high-resolution mass spectrometry (HRMS) and tandem MS. About 50 different transformation products have been identified for ciprofloxacin and norfloxacin. More than 15 products were the first time reported. Taking into consideration of the sequential formation and intensity change of intermediates, the feasible and complete transformation pathways of FQs were proposed. Compared with the photolysis process, the defluorination of FQs was not observed in this system. This work provided abundant information of FQs degradation by persulfate advanced oxidation processes (AOPs) and meanwhile demonstrated the importance of HRMS and on-line MS in mechanism research of AOPs.

5.
Arch Oral Biol ; 109: 104588, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669922

RESUMO

OBJECTIVE: Dental occlusion are frequently changed in clinic. Molecular responses in jaw muscles to aberrant dental occlusion are changes are attractive, yet remain are obscure. DESIGN: Unilateral anterior crossbite (UAC) prostheses were applied to Sprague-Dawley rats and then ceased after two weeks to detect the reactions of the masseter, a representative jaw elevator, and the lateral pterygoid muscle (LPM), a representative jaw depressor. RESULTS: Two weeks of UAC elicited mild injury of the two muscles. Myogenesis and protective reactions were detected as increases in αB-crystallin expression in the masseter after 3 days and in the LPM after 2 weeks, and increases in desmin expression in both muscles after 2 weeks. A switch in fibre types from IIb to IIx occurred in the LPM but not in the masseter. Inflammatory responses, shown by the infiltration of inflammatory cells and increases in TNF-α mRNA expression, and fibrosis responses, shown by increased mRNA expression of Type I and III collagens, appeared very mild in the two muscles. These responses were partially recovered by the cessation of UAC. During the whole process, no obvious changes were observed in mitochondrial function, as indicated by the levels of proliferator-activated receptor γ coactivator 1α, mitofusin-2 and voltage-dependent anion channel. CONCLUSIONS: UAC causes injury and very limited inflammatory and fibrosis adaption in the masseter and LPM. Both muscles respond with myogenesis and protective activity. The LPM responds also with muscle fibre isoform alternations. These alterations were partially recovered by the cessation of dental stimulation at an early stage.

6.
Dalton Trans ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777887

RESUMO

A new photochromic and porous Cd(ii) coordination polymer (CP) has been synthesized by using a robust viologen ligand, named 1-(3-carboxybenzyl)-4,4'-bipyridinium chloride (m-Hbcbpy·Cl) and CdCl2·2H2O. This CP (Cd-bcbpy) shows a fast response and reversible photochromism through the progress of ET due to the formation of viologen radicals. Cd-bcbpy shows a sharp response to blue rays and selectively detects organic amine molecules, which are electron rich, in the solid state due to the electron-deficient properties of m-Hbcbpy·Cl. The detection of organic amine and benzene molecules has been confirmed by the visual color changing phenomenon and luminescence quenching experiment. Cd-bcbpy can detect aniline in very low concentrations (10-4 M). In addition, the structure of Cd-bcbpy maintains stability in aqueous solutions of hydrochloric acid with the pH ranging from 1 to 7. The photo-controlled luminescence properties of this CP, during the coloration-decoloration process, have been studied.

7.
iScience ; 22: 16-27, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31739171

RESUMO

Accurate reference genomes have become indispensable tools for characterization of genetic and functional variations. Here we generated a high-quality assembly of the melon Payzawat using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. The final 12 chromosome-level scaffolds cover ∼94.13% of the estimated genome (398.57 Mb). Compared with the published DHL92 genome, our assembly exhibits a 157-fold increase in contig length and remarkable improvements in the assembly of centromeres and telomeres. Six genes within STHQF12.4 on pseudochromosome 12, identified from whole-genome comparison between Payzawat and DHL92, may explain a considerable proportion of the skin thickness. In addition, our population study showed that melon domesticated at multiple times from whole-genome perspective and melons in China are introduced from different routes. Selective sweeps underlying the genes related to desirable traits, haplotypes of alleles associated with agronomic traits, and the variants from resequencing data enable efficient breeding.

8.
Skelet Muscle ; 9(1): 28, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31757224

RESUMO

BACKGROUND: Low lean body mass is the most important predictor of sarcopenia with strong genetic background. The aim of this study was to uncover genetic factors underlying lean mass development. MATERIALS AND METHODS: We performed a genome-wide association study (GWAS) of fat-adjusted leg lean mass in the Framingham Heart Study (FHS, N = 6587), and replicated in the Women's Health Initiative-African American sub-sample (WHI-AA, N = 847) and the Kansas City Osteoporosis Study (KCOS, N = 2219). We also cross-validated significant variants in the publicly available body mass index (BMI) summary results (N ~ 700,000). We then performed a series of functional investigations on the identified variants. RESULTS: Four correlated SNPs at 6p21.1 were identified at the genome-wide significance (GWS, α = 5.0 × 10-8) level in the discovery FHS sample (rs551145, rs524533, rs571770, and rs545970, p = 3.40-9.77 × 10-9), and were successfully replicated in both the WHI-AA and the KCOS samples (one-sided p = 1.61 × 10-3-0.04). They were further cross-validated by the large-scale BMI summary results (p = 7.0-9.8 × 10-3). Cis-eQTL analyses associated these SNPs with the NFKBIE gene expression. Electrophoresis mobility shift assay (EMSA) in mouse C2C12 myoblast cells implied that rs524533 and rs571770 were bound to an unknown transcription factor in an allelic specific manner, while rs551145 and rs545970 did not. Dual-luciferase reporter assay revealed that both rs524533 and rs571770 downregulated luciferase expression by repressing promoter activity. Moreover, the regulation pattern was allelic specific, strengthening the evidence towards their differential regulatory effects. CONCLUSIONS: Through a large-scale GWAS followed by a series of functional investigations, we identified 2 correlated functional variants at 6p21.1 associated with leg lean mass. Our findings not only enhanced our understanding of molecular basis of lean mass development but also provided useful candidate genes for further functional studies.

9.
Lung Cancer ; 139: 118-123, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31775086

RESUMO

OBJECTIVES: The 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. MATERIALS AND METHODS: Data from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. RESULTS: Expression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients' prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). CONCLUSION: The SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.

10.
Biomaterials ; : 119637, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31776018

RESUMO

Side effect is one of the main factors affecting the success of cancer therapies in clinic. Patients treated with photodynamic therapy (PDT) suffer mainly from the phototoxicity due to the relatively long time blood circulation of the tumor enrichment and they have also to be protected from background light for days after the treatment. Here we introduce a new design of nanophotosensitizers in which the luminescence upconversion nanoparticles loaded with photosensitizers are self-assembled into a nanoball with the aid of a specific pH-sensitive polymer layer containing overloaded photosensitizers and quenching molecules. This design makes the therapy function "off/on" possible, i.e. only imaging during the circulation of the nanoballs ascribing to the near-infrared (NIR) photon upconversion of the nanoballs and the pH-sensitive shell. Activation of PDT solely occurs once the nanoballs are taken up by the cancer cells due to the acidic microenvironment. This design prevents effectively the photodamage of the photosensitizers during enrichment and targeting process of tumor, as validated in vitro and in vivo, which enables imaging-guided PDT treatment of deep-seated tumor in a much more relax and comfortable way for patients. This patient-friendly nanomaterial construction strategy can also be extended to other therapies.

11.
Oxid Med Cell Longev ; 2019: 4010764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737170

RESUMO

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.

12.
Luminescence ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749285

RESUMO

Four core-shell structured nanometre luminescent composites with different kernel sizes and different shell layer thicknesses (SiO2(500) @Eu (phen-Si)(50) , SiO2(500) @Eu (phen-Si)(15) , SiO2(250) @Eu (phen-Si)(5) and SiO2(250) @Eu (phen-Si)(10) ) were made by changing synthesis conditions. Here, initial subscript numbers in parentheses refer to the particle size of the SiO2 core, whereas the final subscript numbers in parentheses refer to shell layer thickness. In these composites, silica spheres of 500 nm or 250 nm were identified as the core. The shell layer was composited of silicon, 1,10-phenanthroline and europium perchlorate, abbreviated as Eu(phen-Si); the chemical formula of phen-Si was phen-N-(CONH (CH2 )Si(OCH2 CH3 )3 )2 . The composites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and infrared spectroscopy. The monodispersed spherical SiO2 showed characteristics of a regular microstructure and a smooth surface, as well as the advantage of dispersity, shown by SEM. The Eu(phen-Si) complex was able to self-assemble into monodispersed SiO2 spheres, as seen using TEM. Fluorescence spectra indicated that the four composites had excellent luminescence properties. Furthermore, composites composed of a SiO2 core and a 250 nm kernel size exhibited stronger fluorescence than 500 nm kernel-sized composites. Fluorescence properties were affected by shell thickness: the thicker the shell, the greater the fluorescence intensity. For the four composites, quantum yield values and fluorescence lifetime corresponded to fluorescence emission intensity data as quantum yield values and fluorescence lifetime were higher, and luminescence properties increased.

13.
Environ Monit Assess ; 191(12): 752, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732799

RESUMO

Tropical regions are characterized by hydrological extreme events, which are likely to be exacerbated by climate change. Therefore, quantifying the extent to which climate change may damage a hydrological system becomes crucial. This paper aims to evaluate the findings from previous research on projected impacts of climate change on hydrological systems located in regions bounded by the Tropic of Cancer and the Tropic of Capricorn. It intends to provide an in-depth understanding of the climatic conditions, applied approaches, climate change impacts on future streamflow, and measures to reduce prediction uncertainty in the tropics. The review revealed that there is a significant variation in the magnitude of climate change impacts on streamflow in the tropics. The reason for the inconsistent trend prediction is that projections are heavily dependent on the trajectory of greenhouse gas emissions, climate model structural differences, and uncertainty of downscaling methods and hydrological models. Therefore, to minimize the uncertainty and maximize confidence in streamflow projections, it is essential to apply multi-member model ensembles and to clarify the adaptation strategy (coping, adjusting, or transforming).

14.
Aging (Albany NY) ; 112019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31754082

RESUMO

There have been an increasing number of functional magnetic resonance imaging (fMRI) reports on brain abnormalities in mild traumatic brain injury (mTBI) at different phases. However, the neural bases and cognitive impairment after acute mTBI are unclear. This study aimed to identify brain functional hubs and connectivity abnormalities in acute mTBI patients and their correlations with deficits in cognitive performance. Within seven days after brain injury, mTBI patients (n=55) and age-, sex-, and educational -matched healthy controls (HCs) (n=41) underwent resting-state fMRI scans and cognitive assessments. We derived functional connectivity (FC) strength of the whole-brain network using degree centrality (DC) and performed Granger causality analysis (GCA) to analyze causal connectivity patterns in acute mTBI. Compared with HCs, acute mTBI patients had significantly decreased network centrality in the left middle frontal gyrus (MFG). Additionally, acute mTBI showed decreased inflows from the left MFG to bilateral middle temporal gyrus (MTG), left medial superior frontal gyrus (mSFG), and left anterior cingulate cortex (ACC). Correlation analyses revealed that changes in network centrality and causal connectivity were associated with deficits in cognitive performance in mTBI. Our findings may help to provide a new perspective for understanding the neuropathophysiological mechanism of acute cognitive impairment after mTBI.

15.
Emerg Microbes Infect ; 8(1): 1574-1583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682177

RESUMO

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR-/- A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.

16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
17.
Pharmazie ; 74(11): 688-693, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739839

RESUMO

Background: Donafenib is a novel compound similar to sorafenib that functions as a multikinase inhibitor. This phase 1b trial aimed to assess the safety, pharmacokinetics and efficacy of donafenib in treating Chinese patients with advanced hepatocellular carcinoma. Methods: From July 2014 to April 2015, 27 eligible advanced hepatocellular carcinoma patients were enrolled in the trial. They were randomly divided into 200 mg and 300 mg bid groups and received these oral doses of donafenib until the appearance of intolerance or disease progression. Results: Overall, donafenib was safe and well tolerated in the two groups, and most adverse events were grade 1 or 2. Elevated transaminase (n=19, 70.4 %), hypocalcemia (n=19, 70.4 %), and skin toxicity (n=17, 63.0 %) were the most frequently encountered adverse events. Donafenib exhibited high variability in pharmacokinetic parameters. Areas under the plasma concentration-time curve from 0-12 h increased disproportionally to the dose escalation. The treatment resulted in partial response in two patients and a stable disease status in 17 patients, and the median time to progression was 120 days for both groups. Conclusion: The results from this phase 1b trial indicate a favorable safety profile and notable anticancer efficacy of donafenib for treating advanced hepatocellular carcinoma. Comparable or better safety and efficacy were observed for a lower dosage of donafenib compared with sorafenib in the literature.

18.
Oncogene ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740785

RESUMO

Increasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-ß1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-ß1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-ß1 than in those with high HBx or high TGF-ß1 and the double-low-expression group. HBx and TGF-ß1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-ß1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial-mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-ß1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-ß1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-ß1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

19.
Mol Med Rep ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31746391

RESUMO

Previous microRNA (miR) microarray analysis revealed that miR­218 is downregulated in cervical cancer tissues. The present study aimed to further evaluate the expression of miR­218 in cervical cancer specimens, determine the association between its expression with disease progression, and investigate the roles of miR­218 in cervical cancer cells. Tissue specimens were obtained from 80 patients with cervical squamous cell carcinoma, 30 patients with high­grade cervical intraepithelial neoplasia [(CIN) II/III] and 15 patients with low­grade CIN (CINI); in addition, 60 plasma samples were obtained from patients with cervical cancer, and 15 normal cervical tissue specimens and 30 plasma samples were obtained from healthy women. These samples were used for analysis of miR­218 expression via reverse transcription­-quantitative PCR. In addition, tumor cells were transfected with miR­218 mimics, human papillomavirus (HPV)16 E6/E7 small interfering RNA, or their respective negative controls to determine the viability, colony formation, migration and invasion of cells using MTT, colony formation, wound healing and Transwell assays, respectively. Target genes of miR­218 were bioinformatically predicted and analyzed using Gene Ontology (GO) terms. The results revealed that miR­218 was downregulated in the tumor tissues and plasma of patients with cervical cancer, with expression associated with the advanced clinicopathological characteristics of patients, including HPV positivity, tumor size, blood vessel invasion and lymph node metastasis. Furthermore, miR­218 overexpression reduced tumor cell viability and xenograft growth, and suppressed tumor cell migration and invasion. HPV was detected in 75% of the 80 patients with cervical cancer, and HPV positivity was inversely associated with miR­218 expression. In addition, bioinformatics analysis predicted that roundabout guidance receptor 1 (ROBO1) was a target gene of miR­218; miR­218 overexpression significantly reduced ROBO1 levels. Furthermore, GO analysis revealed that ROBO1 was involved in regulating cell proliferation, adhesion and migration, and the cell cycle. In conclusion, the findings of the present study suggested that miR­218 may possess antitumor activities in cervical cancer.

20.
Ann Noninvasive Electrocardiol ; : e12731, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746517

RESUMO

Isolated ventricular noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven meshwork. Its mortality and morbidity are high, including heart failure, thromboembolic events, and ventricular arrhythmias. Isolated right ventricular noncompaction was reported rarely, especially that causes pulmonary embolism and ventricular tachycardia. We describe a case of isolated noncompaction of the right ventricular causing pulmonary embolism and ventricular tachycardia.

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