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1.
Sci Rep ; 11(1): 8208, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859270

RESUMO

The vestibular receptor of cupula acts an important role in maintaining body balance. However, the cupula buried in the semicircular canals (SCCs) will be destroyed if it is detached from the relevant environment. The mechanical properties of human cupula still remain ambiguous. In this paper, we explored the cupula responses changing with temperature by experiments and numerical simulation of SCCs model. We obtained 3 volunteers' nystagmus induced by constant angular acceleration when the temperature of volunteers' SCCs was 36 °C and 37 °C respectively. The slow-phase velocity of 3 volunteers decreased by approximately 3°/s when the temperature of SCCs reduced by 1 °C, which corresponded to the reduction of cupula deformation by 0.3-0.8 µm in the numerical model. Furthermore, we investigated the effects of the variation of endolymphatic properties induced by temperature reduction on cupula deformation through numerical simulation. We found that the decrease of cupula deformation was not caused by the change of endolymphatic properties, but probably by the increase of cupula's elastic modulus. With the temperature reducing by 1 °C, the cupula's elastic modulus may increase by 6-20%, suggesting that the stiffness of cupula is enhanced. This exploration of temperature characteristic of human cupula promotes the research of alleviating vestibular diseases.

2.
Zhongguo Gu Shang ; 34(2): 180-90, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666009

RESUMO

OBJECTIVE: To compare clinical effect of cannulated screw and bone plate for the treatment of humeral fracture of greater tuberosity. METHODS: From January 2010 to January 2020, clinical trial literatures on the treatment of humeral tuberosity fractures with cannulated screw and bone plate were searched by PubMed, EMbase, Cochrane Library, Wanfang, CNKI, CBM Database, VIP Database and other databases. Independent literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Revman5.2 software was used to perform Meta analysis. RESULTS: Totally 5 clinical randomized controlled trials and 12 cohort studies were selected, including 1 068 patientsin which 559 patients were treated by cannulated screw internal fixation and 509 patients treated by bone plate internal fixation. Meta analysis resluts showed that there were satistical differences in operation time[MD=-23.03, 95% CI(-29.69, -16.36), P<0.000 1], blood loss[MD=-36.39, 95% CI(-53.73, -19.04), P<0.000 1], hospital stay[MD=-1.86, 95%CI(-3.09, -0.64), P=0.003], fracture healing time [MD=-2.23, 95% CI (-4.27, -0.18), P=0.03], postoperative incidence of infection [OR=0.17, 95%CI (0.03, 0.97), P=0.05], failure rate of internal fixation [OR=3.56, 95% CI (1.29, 9.81), P=0.01] bwteen two groups. While there were no differences in postoperative visual analogue scale (VAS)[MD=-1.34, 95% CI (-2.77, 0.09), P=0.07], American Shoulder and Elbow Surgeons(ASES)[MD=0.26, 95% CI(-6.43, 6.96), P=0.94], Constant shoulder score [MD=-4.05, 95% CI(-8.51, 0.42), P=0.08], excellent rate of Constant shoulder score[MD=-1.30, 95% CI(0.46, 3.72), P=0.62], excellent rate of Neer shoulder joint score[OR=2.04, 95% CI(0.97, 4.28), P=0.06], total complication rate[OR=1.50, 95% CI (0.42, 5.35), P=0.53], incidence of postoperative pain[OR=0.74, 95% CI(0.04, 14.49), P=0.84] and incidence of postoperative acromion syndrome [OR=0.88, 95% CI (0.02, 40.63), P=0.95] between two groups. CONCLUSION: Compared with bone plate, cannulated screw for the treatment of humeral fracture of greater tuberosity has advantages of shorter opertaion time, less blood loss, shorter hospital stay, lower incidence rate of postopertaive infection, and more benefit for fracture healing.


Assuntos
Placas Ósseas , Fraturas do Úmero , Parafusos Ósseos , Fixação Interna de Fraturas , Humanos , Fraturas do Úmero/cirurgia , Úmero , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
Brain Behav Immun ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737172

RESUMO

Impaired amyloid-ß (Aß) clearance is believed to be a primary cause of Alzheimer's disease (AD), and peripheral abnormalities in Aß clearance have recently been linked to AD pathogenesis and progression. Data from recent genome-wide association studies have linked genetic risk factors associated with altered functions of more immune cells to AD pathology. Here, we first identified correlations of Smad3 signaling activation in peripheral macrophages with AD progression and phagocytosis of Aß. Then, manipulating the Smad3 signaling regulated macrophage phagocytosis of Aß and induced switch of macrophage inflammatory phenotypes in our cell cultures. In our mouse models, flag-tagged or fluorescent-dye conjugated Aß was injected into the lateral ventricles or tail veins, and traced. Interestingly, blocking Smad3 signaling efficiently increased Aß clearance by macrophages, reduced Aß in the periphery and thereby enhanced Aß efflux from the brain. Moreover, in our APP/PS1 transgenic AD model mice, Smad3 inhibition significantly attenuated Aß deposition and neuroinflammation, and ameliorated cognitive deficits, probably by enhancing the peripheral clearance of Aß. In conclusion, enhancing Aß clearance by peripheral macrophages through Smad3 inhibition attenuated AD-related pathology and cognitive deficits, which may provide a new perspective for understanding AD and finding novel therapeutic approaches.

4.
Dalton Trans ; 50(11): 4045-4052, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33666620

RESUMO

It is well-known that the excellent cycling stability and high energy density of electrode materials is very important for supercapacitors. However, their actual performance falls far behind and does not satisfy the practical demand. In this study, we synthesized NiCo2S4 nanowire bundles on a nickel foam via facile hydrothermal routes. The as-obtained product as an electrode material possesses excellent specific surface area, which suggests that numerous active sites on the electrode surface can shorten the diffusion channel of ions. The assembled asymmetric supercapacitor delivers an energy density of 57.36 W h kg-1 at 1412.92 W kg-1. Also, it exhibits excellent mechanical stability even at different bending angles.

5.
Oncologist ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675070

RESUMO

PURPOSE: The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). PATIENTS AND METHODS: We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1-positive (LOX-1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. RESULTS: Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR (<2.7) displayed significantly increased OS in the discovery cohort (59.8 months vs. 21 months), the validation group (38.0 months vs. 23.6 months), and the total cohort (44.1 months vs. 22.0 months). A Cox proportional hazards model was used to combine Cancer of the Liver Italian Program (CLIP) score with discretized NAR. C-index illustrated that NAR-integrated CLIP score was the best model compared with NAR and CLIP score. Furthermore, NAR-CLIP presented superior predictive capacity for 10-, 20-, 30-, 40-, 50-, and 60-month survival compared with CLIP score by survival receiver-operator characteristic analysis in the discovery cohort, validation cohort, and total cohort. NAR was significantly associated with LOX-1+ PMN-MDSCs by linear regression. CONCLUSION: This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. IMPLICATIONS FOR PRACTICE: The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1-positive polymorphonuclear myeloid-derived suppressor cells.

6.
Patient Educ Couns ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33583647

RESUMO

OBJECTIVE: We examined the relationship between patient-centered communication and cancer risk information avoidance and estimated the mediating role of self-efficacy in this relationship. METHODS: Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N = 2033), this study aims to provide a comprehensive understanding of the relationship between patient-centered communication and cancer risk information avoidance via correlation analysis, stepwise regression models, and mediation analysis. RESULTS: Patient-centered communication was significantly negatively associated with cancer risk information avoidance (ß= -0.09, p < 0.01) after controlling for gender, income, education, and cancer risk perception. Self-efficacy fully mediated the relationship of patient-centered communication with cancer risk information avoidance. CONCLUSION: Patient-centered communication can improve patients' self-efficacy, thereby preventing them from avoiding cancer risk information. PRACTICE IMPLICATIONS: The negative relationship between patient-centered communication and cancer risk information avoidance substantiates that improving patient-centered communication is a promising approach to support caregivers in their activities, reduce patients' subjective cancer burden, and even improve their health. To address cancer-related issues, policymakers can consider interventions from the external environment and internal personal cognition perspectives.

7.
Int J Biol Sci ; 17(2): 498-513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613108

RESUMO

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/ß-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

8.
Commun Biol ; 4(1): 252, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637832

RESUMO

In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.

9.
Oral Dis ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33503275

RESUMO

BACKGROUND: Cyclin-dependent kinase 7 (CDK7) has been critically linked to human cancer. However, the roles of CDK7 in head and neck squamous cell carcinoma (HNSCC) remain incompletely known. Here, we sought to dissect the functions of CDK7 underlying HNSCC tumorigenesis and explore whether pharmacological inhibition of CDK7 could induce anti-cancer effects. METHODS: CDK7 expression was measured in a panel of HNSCC cell lines with p53 mutation and 20 pairs of HNSCC samples and adjacent non-tumor tissues. Genetic targeting and pharmacological inhibition of CDK7 were conducted to dissect the biological roles of CDK7 in p53-mutated HNSCC cells. An HNSCC xenograft model was developed to determine the therapeutic effects of THZ1 in vivo. Potential genes and pathways responsible for therapeutic effects of THZ1 were identified by genome-wide RNA-sequencing and bioinformatics interrogations. RESULTS: CDK7 expression was significantly elevated in cancerous cells and samples as compared with their adjacent non-tumor counterparts. Impaired cell proliferation, migration, and invasion as well increased apoptosis were observed in cells upon CDK7 knockdown or THZ1 exposure. THZ1 administration potently inhibited tumor overgrowth in vivo. Mechanistically, hundreds of genes enriched in cell proliferation, apoptosis, and cancer-related categories were identified to be potentially mediated the therapeutic effects of THZ1 in HNSCC. CONCLUSION: Our findings reveal that CDK7 might serve as a novel putative pro-oncogenic gene underlying HNSCC tumorigenesis and therapeutic targeting of CDK7 might be a promising strategy for p53-mutated HNSCC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33401394

RESUMO

The purpose of this paper is to summarize the research themes and hotspots of safety signs research between 1990 and 2019 through the scientometric analysis method. In total, 3102 articles of literature from the Web of Science core database were analyzed by the CiteSpace visualization tool and the results were displayed in mapping knowledge domains. The overall characteristics analysis showed that safety sign is an emerging research field in a rapid development stage-81.4% of the literature works were published in the past ten years, and the United States was in the leading position, followed by China and Canada. The keyword co-occurrence analysis indicated that traffic signs and driving safety were the most popular research topics and have been combined with simulation technology in recent years, whereby individual mental health has been added as an influential factor. The journals and category co-citation analysis showed that the safety signs research involved many subjects, mainly engineering, transportation and public safety. The results indicated that the safety signs research is multi-disciplinary, and it will continue to develop in various scientific domains in the future. The conclusions can provide help and reference for potential readers, as well as help with the sustainable development of safety signs research.


Assuntos
Condução de Veículo , Diretórios de Sinalização e Localização , Segurança , Humanos
11.
Artigo em Inglês | MEDLINE | ID: mdl-33460368

RESUMO

Heterogeneous Face Recognition (HFR) refers to matching cross-domain faces and plays a crucial role in public security. Nevertheless, HFR is confronted with challenges from large domain discrepancy and insufficient heterogeneous data. In this paper, we formulate HFR as a dual generation problem, and tackle it via a novel Dual Variational Generation (DVG-Face) framework. Specifically, a dual variational generator is elaborately designed to learn the joint distribution of paired heterogeneous images. However, the small-scale paired heterogeneous training data may limit the identity diversity of sampling. In order to break through the limitation, we propose to integrate abundant identity information of large-scale visible data into the joint distribution. Furthermore, a pairwise identity preserving loss is imposed on the generated paired heterogeneous images to ensure their identity consistency. As a consequence, massive new diverse paired heterogeneous images with the same identity can be generated from noises. The identity consistency and identity diversity properties allow us to employ these generated images to train the HFR network via a contrastive learning mechanism, yielding both domain-invariant and discriminative embedding features. Concretely, the generated paired heterogeneous images are regarded as positive pairs, and the images obtained from different samplings are considered as negative pairs. Our method achieves superior performances over state-of-the-art methods on seven challenging databases belonging to five HFR tasks, including NIR-VIS, Sketch-Photo, Profile-Frontal Photo, Thermal-VIS, and ID-Camera.

12.
Meat Sci ; 175: 108432, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453553

RESUMO

This study was designed to evaluate changes in color following pork chop supplementation with porcine hemin, astaxanthin and paprika red in response to repeated freeze-thaw processes. Surface color analyses revealed that hemin significantly enhanced the appearance of the pork chops (P < 0.05), and the coloring efficiency of 0.10% hemin was similar to that of 0.20% astaxanthin and 0.08% paprika red. Sensory evaluations conducted on both raw and fried chops showed that hemin and astaxanthin significantly enhanced the overall acceptability of the chops before and after cooking. The color stability of the pork chops was also evaluated, and the results suggested that the hemin-colored chops were the most stable among the three, upon repeated freeze-thaw cycles. The electronic nose showed that the odor of the hemin-colored samples after 0, 3, and 7 freeze-thaw cycles was better than that of the other two groups. In conclusion, hemin may be a superior supplement for the large scale preparation of prepared pork chop.

13.
Biomaterials ; 268: 120559, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310538

RESUMO

Innovative neurotechnology must be leveraged to experimentally answer the multitude of pressing questions in modern neuroscience. Driven by the desire to address the existing neuroscience problems with newly engineered tools, we discuss in this review the benefits of flexible electronics for neuroscience studies. We first introduce the concept and define the properties of flexible and stretchable electronics. We then categorize the four dimensions where flexible electronics meets the demands of modern neuroscience: chronic stability, interfacing multiple structures, multi-modal compatibility, and neuron-type-specific recording. Specifically, with the bending stiffness now approaching that of neural tissue, implanted flexible electronic devices produce little shear motion, minimizing chronic immune responses and enabling recording and stimulation for months, and even years. The unique mechanical properties of flexible electronics also allow for intimate conformation to the brain, the spinal cord, peripheral nerves, and the retina. Moreover, flexible electronics enables optogenetic stimulation, microfluidic drug delivery, and neural activity imaging during electrical stimulation and recording. Finally, flexible electronics can enable neuron-type identification through analysis of high-fidelity recorded action potentials facilitated by its seamless integration with the neural circuitry. We argue that flexible electronics will play an increasingly important role in neuroscience studies and neurological therapies via the fabrication of neuromorphic devices on flexible substrates and the development of enhanced methods of neuronal interpenetration.

14.
Food Chem ; 340: 128209, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032146

RESUMO

To improve the stabilities of low methoxy pectin (LMP) stabilized O/W emulsions for the delivery of bioactive substances, LMP was firstly modified with soy peptide (SP), corn peptide (CP) and whey protein peptide (WPP), respectively, by using dry-heat method, then the properties of LMP-peptide complexes stabilized O/W emulsions were characterized and the in vitro digestion of emulsions with ß-carotene was test to evaluate the potential applications. LMP-peptide complexes were formed by covalent bonds according to FT-IR spectroscopy. Compared to LMP stabilized emulsions, LMP-peptide complexes stabilized emulsions had smaller droplet sizes and higher stabilities in the changed pH value, temperature and ionic strength. Based on the results of in vitro digestion tests, LMP-SP and LMP-WPP obtained by incubating LMP with peptides at 60 °C for 12 h at the weight ratio of 4:1 were more suitable for the preparation of O/W emulsions to deliver camellia oil and ß-carotene.


Assuntos
Digestão , Portadores de Fármacos/química , Pectinas/química , Peptídeos/química , beta Caroteno/química , beta Caroteno/metabolismo , Emulsões , Micelas , Proteínas de Plantas/química , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Am J Cancer Res ; 10(11): 3622-3643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294258

RESUMO

Estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, was reported to be highly associated with the progression and tumorigenesis of several human malignancies. However, the biological role and underlying molecular mechanisms of ERRα in pancreatic cancer (PC) remain unknown. The present study demonstrated that ERRα was significantly overexpressed in PC tissues and cell lines. Its high expression was correlated with tumor size, distant metastasis, TNM stage, tumor differentiation and poor prognosis of PC. Subsequent functional assays showed that ERRα promoted PC cell proliferation, tumor growth, as well as migration and invasion via activating the epithelial-mesenchymal transition. In addition, knockdown of ERRα induced apoptosis and G0/G1 cell cycle arrest in PC cells. Plasminogen activator inhibitor 1 (PAI1) was identified by RNA sequencing, knockdown of which could suppress the cell proliferation, migration and invasion that promoted by ERRα overexpression. Further mechanistic investigation using chromatin immunoprecipitation and dual-luciferase reporter assays revealed that ERRα could bind to the PAI1 promoter region and transcriptionally enhance PAI1 expression. Moreover, our data indicated that ERRα played its oncogenic role in PC via activating the MEK/ERK pathway. Taken together, our study demonstrates that ERRα promotes PC progression by enhancing the transcription of PAI1 and activation of the MEK/ERK pathway, pointing to ERRα as a novel diagnostic and therapeutic target for PC.

16.
RNA Biol ; : 1-10, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295243

RESUMO

N6-methyladenosine (m6A) has emerged as a crucial epitranscriptomic mark which regulates a broad spectrum of physiological processes including stem cell differentiation. m6A-binding YTHDF proteins have recently been proposed to mediate differentiation of leukemia cell in a redundant manner. However, whether these proteins play semblable roles in pluripotent stem cell remain largely unknown. Here, we showed the differential functions of YTHDF1 and YTHDF3 in controlling the differentiation of embryonic stem cells (ESCs). Depletion of YTHDF3 in ESCs resulted in loss of pluripotency with accelerated expressions of marker genes involved in formation of three germ layers. Phenotypic and transcriptomic analyses revealed that loss of YTHDF1 led to dramatic impairment of cardiomyocytes (CMs) differentiation, accompanied by downregulated CM-specific genes. While, knockdown of YTHDF3 accelerated differentiation through facilitating the expressions of CM-specific gene. Notably, YTHDF3 appears to modulate cellular differentiation partially through suppression of YTHDF1, supporting the distinguishable but interrelated roles of YTHDF1 and YTHDF3 in cell fate determination.

17.
Cancer Lett ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33279623

RESUMO

CD45+CD71+ erythroid cells generated through splenic extramedullary erythropoiesis have recently been found to suppress anti-infection and tumor immunity in neonates and adults with malignances. However, their role in tumor microenvironment has not been investigated. In the present study, we found that the number of CD45+CD71+ erythroid cells was significantly elevated in hepatocellular carcinoma (HCC) tissues compared to that in paratumor region and circulation. Additionally, they were more abundant in HCC tissues compared to some immune suppressive cells as well as CD45-CD71+ erythroid cells. CD45+CD71+ erythroid cells suppressed T cells through generation of reactive oxygen species, IL-10, and TGF-ß in a paracrine and cell-cell contact manner, and their suppressive effect was stronger than that of myeloid-derived suppressor cells. The abundance of CD45+CD71+ erythroid cells in tumor tissue, as illustrated via immunofluorescence, predicted disease-free survival and overall survival, and its prognostic value was better than that of Cancer of the Liver Italian Program score. This study demonstrated that accumulation of intratumoral CD45+CD71+ erythroid cells in HCC tissues could play a superior immunosuppressive role in tumor microenvironment and may serve as a valuable biomarker to predict recurrence of HCC.

18.
Oncol Res ; 28(5): 559-560, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33349309

RESUMO

Overexpression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) has been detected in many cancer types and is considered to foster tumor progression. However, the role of TRAF4 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that TRAF4 was highly expressed in HCC cell lines and HCC tissues compared with normal liver cell lines and adjacent noncancerous tissues. TRAF4 overexpression in HCC tissues was correlated with tumor quantity and vascular invasion. In vitro studies showed that TRAF4 was associated with HCC cell migration and invasion. An in vivo study verified that TRAF4 overexpression facilitated metastasis in nude mice. In addition, overexpressed TRAF4 promoted the phosphorylation of Akt and induced Slug overexpression, leading to downregulated E-cadherin and upregulated vimentin, while silencing TRAF4 moderated the phosphorylation of Akt and repressed the expression of Slug, which resulted in upregulated E-cadherin and downregulated vimentin. These effects were inversed after pretreatment of the PI3K/Akt inhibitor LY294002 or overexpression of constitutively active Akt1. Our study demonstrated that TRAF4 was involved in promoting HCC cell migration and invasion. The process was induced by the EMT through activation of the PI3K/Akt signaling pathway.

19.
Int J Nanomedicine ; 15: 10285-10304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376322

RESUMO

Background: Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations. Purpose: A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects. Methods: The MSNCA@GODOX-HA was constructed by MSNCA (loading CA via physical diffusion) and GODOX-HA (modified with HA and loading DOX via π-π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively. Results: The MSNCA@GODOX-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSNCA@GODOX-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process. Conclusion: The establishment of the MSNCA@GODOX-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.


Assuntos
Acroleína/análogos & derivados , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Grafite/química , Nanopartículas/química , Dióxido de Silício/química , Acroleína/química , Acroleína/farmacologia , Doxorrubicina/química , Humanos , Células MCF-7 , Porosidade , Espécies Reativas de Oxigênio/metabolismo
20.
J Mol Neurosci ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226577

RESUMO

Hypoxia-inducible factor-3α (HIF-3α), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF-3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF-3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10-4.44; P = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02-2.97, P = 0.04; A vs G OR = 1.48, 95% CI, 1.05-2.07, P = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases (P < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.

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