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1.
Cancer Med ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620152

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan-Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence-activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan-Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2-siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119520, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33582436

RESUMO

High pathologic tumor-node-metastasis (pTNM) stage grade or Fuhrman grade indicates poor oncological outcome in renal cell carcinoma (RCC). Early diagnosis and screening of these RCCs and adjust surgical planning accordingly are greatly beneficial to patients. Raman spectroscopy is a highly specific fingerprint spectrum on molecular level, pretty appropriate for label-free and noninvasive cancer diagnosis. In this work we established a Raman spectrum-based supporting vector machine (SVM) model to accurately ex vivo distinguish human renal tumor from normal tissues and fat with an accuracy of 92.89%. The model can also be used to determine tumor boundary, showing consistent results to pathological staining analysis. This method can be additionally used to accomplish the classification purposes of renal tumor subtypes and grades with an accuracy of 86.79% and 89.53%, respectively. Therefore, we prove that Raman spectroscopy has great potential in the rapid and accurate clinical diagnosis of renal cancers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33587586

RESUMO

Bioinspired nanoporous membranes show great potential in ionic separation and water filtration by offering high selectivity with less permeation resistance. However, complex processes always limit their applications. Here, we report a convenient approach to introduce ionic selective channels in a micron-thick polycarbonate membrane through swift heavy ion irradiation accompanied by UV sensitization and pulsed-electrical etching. The characteristic dimension of channels was tuned through regulating energy loss of the incident ion and UV sensitization time of the membrane, resulting in the sub-nanoporous membranes with mean channel diameter ranging from <2.4 to 9.7 Å. These membranes showed the voltage-activated ionic transport properties associated with the dehydration effect, and the corresponding I-V characteristics were related to ionic strength, solution pH, ionic type, and channel diameter. It was found that the transmembrane conduction of multivalent ions was severely suppressed compared to monovalent ions, until the size of the membrane channel was comparable to the hydrated diameter of multivalent ions. Ionic sieving experiments also demonstrated the excellent ionic valence selectivity of the membrane. Even for the membrane with a channel diameter close to 1 nm, the Li+/Mg2+ separation ratio was still as high as 40, and an even higher separation ratio was found for Li+/La3+ (>3000).

4.
J Int Med Res ; 49(1): 300060520983585, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33478308

RESUMO

OBJECTIVE: For patients with atherosclerotic renal artery stenosis (ARAS), the role of percutaneous transluminal renal angioplasty (PTRA) remains inconclusive. This study aimed to comparatively evaluate the benefits of best medical therapy (BMT) plus PTRA and BMT alone in treating ARAS. METHODS: We performed a systematic review and meta-analysis, and searched for all randomized, controlled trials that reported patients with ARAS. The effectiveness and safety in the BMT plus PTRA and BMT alone groups were estimated, taking into account hypertension, stroke, renal events, cardiac events, and mortality. RESULTS: Nine randomized, controlled trials involving 2309 patients were included. In the BMT plus PTRA group, the incidence of refractory hypertension was significantly lower compared with that in the BMT alone group (odds ratio 0.09; 95% confidence interval 0.01, 0.70). However, there were no significant differences in the rates of stroke, renal events, cardiac events, cardiac mortality, and all-cause mortality between the two groups. CONCLUSIONS: PTRA plus BMT improves blood pressure in patients with ARAS, but there is insufficient evidence for this therapy in improving stroke, renal events, cardiac events, and cardiac and all-cause mortality.

5.
Int J Implant Dent ; 6(1): 78, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33230662

RESUMO

OBJECTIVES: To compare the accuracy of dynamic navigation (DN) with a static surgical guide (SSG) for dental implant placement and the influence factors such as the experience of the surgeon and the implant sites. METHODS AND MATERIALS: A total of 38 implants, which underwent the dynamic navigation, and 57 implants which underwent a static surgical guide were enrolled in the retrospective study. Coronal deviation, apical deviation, and angular deviation were compared between the DN and SSG groups, along with the different experience level of surgeons and implant sites in the DN group. RESULTS: There were no statistically significant differences between the DN and SSG groups, and the experience level of the surgeons and implant sites in the DN group. However, the apical deviation of the DN was slightly higher than the SSG group in the anterior teeth (P = 0.028), and the angular deviation of DN was smaller than the SSG group in the molar. CONCLUSION: Dynamic navigation can achieve accurate implant placement as well as the static surgical guide. Additionally, the experience level of the surgeon and implant site do not influence the accuracy of dynamic navigation, while the accuracy of DN seems higher than the SSG in molar.

6.
Theranostics ; 10(23): 10791-10807, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929380

RESUMO

Background: Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) that are derived from exons or introns by special selective shearing. circRNAs have been shown to play critical roles in various human cancers. However, their roles in renal cell carcinoma (RCC) and the underlying mechanisms remain largely unknown. Methods: A novel circRNA-circPTCH1, was identified from a microarray analysis of five paired RCC tissues. Then, we validated its expression and characterization through qRT-PCR, gel electrophoresis, RNase R digestion assays and Sanger sequencing. Functional experiments were performed to determine the effect of circPTCH1 on RCC progression both in vitro and in vivo. The interactions between circPTCH1 and miR-485-5p were clarified by RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: We observed that circPTCH1 was up-regulated in RCC cell lines and tumor samples, and higher levels of circPTCH1 were significantly correlated with worse patient survival, advanced Fuhrman grade and greater risk of metastases. Elevated circPTCH1 expression led to increased migration and invasion of RCC cells both in vitro and in vivo whereas silencing circPTCH1 decreased migration and invasion and impeded the epithelial-mesenchymal transition (EMT) of RCC cells. Mechanistically, we elucidated that circPTCH1 could directly bind miR-485-5p and subsequently suppress expression of the target gene MMP14. Conclusion: circPTCH1 promotes RCC metastasis via the miR-485-5p/MMP14 axis and activation of the EMT process. Targeting circPTCH1 may represent a promising therapeutic strategy for metastatic RCC.

7.
Waste Manag ; 116: 1-8, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32781407

RESUMO

Investigations of stabilized/solidified sediment (S/S sediment) by simulated field-construction processes (crushing and filling) are fundamental to evaluating the potential reuse as fill materials. A series of tests were conducted on the samples prepared from S/S sediment grains (SG), which was obtained by crushing the cement treated sediment. By sampling the SG with different field-curing durations (t1: 28, 35, 56 and 98 days) and measuring them by unconfined compressive strength (UCS) tests, the effect of t1 on the UCS was investigated. By continually curing the samples prepared from the SG with 28 field-curing days in laboratory for an additional 7, 28, 35 and 70 days (t2) and subjecting them to UCS and tank leaching tests with different ambient (leachate) pH values (1, 4, 7, 10 and 14), the effect of t2 and ambient pH was evaluated. Increasing t1 and t2 was found to significantly influence the strength of SG, which highlights the importance of an appropriate curing period. The releases of the metals (As, Cr, Cu, Zn, Pb, Ni, and Hg) in the SG exhibited a strongly pH-dependence but less correlation with t2. Neutral conditions (pH = 7) offered the best immobilization capacity for Cu; As, Cr, Ni and Zn exhibited the lowest release at pH = 10; the release of Pb decreased moderately with increasing pH. The S/S sediment complied with the acceptance criteria in terms of metal release and can be regarded as an environmentally friendly fill material. The results highlight the technical feasibility of stabilized sediment recycling in aquatic environment projects.


Assuntos
Metais Pesados/análise , China , Materiais de Construção , Lagos , Reciclagem
8.
Anal Chim Acta ; 1125: 57-65, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32674781

RESUMO

Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are three emerging and re-emerging coronaviruses (CoVs). Symptoms caused by these three viruses are extremely similar, including acute diarrhea, vomiting and even death in piglets. To date, strict biosecurity is still the most effective disease prevention and control measures, and the early detection of pathogens is the most important link. Here, we developed a microfluidic-RT-LAMP chip detection system for the first time, which could detected PEDV, PDCoV and SADS-CoV simultaneously, and had advantages of rapid, simple, sensitive, high-throughput, and accurate at point-of-care settings. The lowest detection limits of the microfluidic-RT-LAMP chip method are 101 copies/µL, 102 copies/µL and 102 copies/µL for PEDV, PDCoV and SADS-CoV, respectively. The whole detection procedure can be finished rapidly in 40 min without any cross-reaction with other common swine viruses. A total of 173 clinical swine fecal samples characterized with diarrheal symptoms were used to evaluate the performance of the newly developed system, which presented good stabilities (C.V.s<5%) and specificities (100%), and possessed sensitivities of 92.24%, 92.19% and 91.23% for PEDV, PDCoV and SADS-CoV respectively. In summary, the established microfluidic-RT-LAMP chip detection system could satisfy the demanding in field diagnoses, which was suitable for promotion in remote areas due to its fast, portable and cost-effective characters.


Assuntos
Coronavirus/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/análise , Alphacoronavirus/genética , Alphacoronavirus/isolamento & purificação , Animais , Coronavirus/isolamento & purificação , Diarreia/diagnóstico , Diarreia/veterinária , Diarreia/virologia , Fezes/virologia , Dispositivos Lab-On-A-Chip , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , RNA Viral/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos
9.
Artigo em Inglês | MEDLINE | ID: mdl-32687004

RESUMO

OBJECTIVE: To report our preliminary results of thermal ablation, including microwave and radiofrequency ablation assisted laparoscopic partial nephrectomy for cT1b renal tumors. MATERIAL AND METHODS: A total of 56 patients with cT1b renal tumors who underwent microwave ablation or radiofrequency ablation assisted laparoscopic partial nephrectomy between January 2014 and May 2018 were enrolled. Thirty of them underwent microwave ablation assisted laparoscopic partial nephrectomy (MWA-LPN group), and the other 26 received radiofrequency ablation assisted laparoscopic partial nephrectomy (RFA-LPN group). Baseline, perioperative and follow-up data were compared between the two groups. RESULTS: There were no statistical differences with respect to patients' gender, age, tumor size, RENAL score, BMI and estimated glomerular filtration rate between the MWA-LPN and RFA-LPN group, nor were any differences observed in warm ischemia time, post-operative complications and hospital stay. Patients in the MWA-LPN group had shorter median operative time (p = .012), less estimated blood loss (p = .023). Median follow-up was 36 months (range 12-64). Three-year cancer-specific and progression-free survival was 100% and 96.4%. The overall kidney recurrence rate was 3.6% in the present study. CONCLUSIONS: Thermal ablation assisted laparoscopic partial nephrectomy is a safe, effective nephron-sparing treatment which provides acceptable results for selective cT1b renal tumors.

10.
Cell Prolif ; 53(7): e12853, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32537867

RESUMO

BACKGROUND: Hypoxia-inducible factors (HIFs) are thought to play important roles in the carcinogenesis and progression of VHL-deficient clear cell renal cell carcinoma (ccRCC). METHODS: The roles of HIF-1/2α in VHL-deficient clear cell renal cell carcinoma were evaluated by bioinformatics analysis, immunohistochemistry staining and Kaplan-Meier survival analysis. The downstream genes that counteract the cancer-promoting effect of HIF were analysed by unbiased proteomics and verified by in vitro and in vivo assays. RESULTS: There was no correlation between the high protein level of HIF-1/2α and the poor prognosis of ccRCC patients in our large set of clinical data. Furthermore, NDRG1 was found to be up-regulated by both HIF-1α and -2α at the cellular level and in ccRCC tissues. Intriguingly, the high NDRG1 expression was correlated with lower Furman grade, TNM stage and longer survival for ccRCC patients compared with the low NDRG1 expression. In addition, NDRG1 suppressed the expression of series oncogenes as well as the proliferation, metastasis and invasion of VHL-deficient ccRCC cells in vitro and vivo. CONCLUSIONS: Our study demonstrated that HIF downstream gene of NDRG1 may counteract the cancer-promoting effect of HIF. These results provided evidence that NDRG1 may be a potential prognostic biomarker as well as a therapeutic target in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Proteínas de Ciclo Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Renais/genética , Regulação para Cima/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gravidez , Ativação Transcricional/genética , Adulto Jovem
11.
Transl Androl Urol ; 9(2): 646-653, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32420171

RESUMO

Correspondence to: Yonghui Chen; Wei Xue. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. Email: cyh1488@163.com; xuewei@renji.com. Background: Aberrantly expressed microRNAs play important biological functions in the pathogenesis, progression and metastasis of numerous malignancies. Thus, further identification of these non-coding transcriptions is warranted. Methods: miRNAs expression data of renal cell carcinoma (RCC) as well as the normal renal tissue samples was downloaded from TCGA and GEO database, and was analyzed by both computational and experimental approaches. The bio-functional role of the miRNA was then moreover identified by over-expression and inhibition assays. Beyond that, Western blots, luciferase assays, along with immunohistochemistry (IHC) tests were conducted for further study of the potential mechanisms. Results: In this study, a novel regulatory miRNA, miR-30a-3p, was identified along with its biological function as well as prognostic value in RCC. Functionally, miR-30a-3p inhibits RCC cell invasion and migration. miR-30a-3p targets autophagy related 12 (ATG12), which we confirmed by luciferase reporter assays and Western blotting. Conclusions: In conclusion, miR-30a-3p, as a new prognostic marker in RCC, down-regulates RCC cell invasion and migration by targeting ATG12. This consistently improves the overall survival of RCC patients.

12.
Sci Total Environ ; 733: 138551, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32422459

RESUMO

Management strategies for the safe disposal of contaminated dredged marine sediment constitute a global-scale environmental issue. The stabilization/solidification method was investigated as a sustainable approach to the recycling of the sediment as a construction material. A systematic study of the factors affecting the mechanical performance and contaminant release was performed. The physico-chemical variables selected to assess the potential re-use of the sediment treated with Ordinary Portland cement (OPC) and Ground Granulated Blast Furnace Slag (GGBS) in an aquatic environment were: curing duration (7, 28, 56 and 98 days), curing temperature (5, 20 and 40 °C) and ambient (leachate) pH (1, 4, 7 and 10). Unconfined compressive strength (UCS) tests were conducted and extended-duration tank leaching tests were used to characterize the long-term leaching of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Ba, Pb. The results showed that S/S methods provide excellent immobilization of metals in marine sediment at a pH range of 4 to 10. Immobilization efficiencies of >99.9% for Mn, Fe, Zn, As, Ba, Pb and >97.8% for Al, Cu and Zn are reported over 100 days. GGBS replacement is an effective way to further improve sediment properties by enhancing strength, mitigating sediment alkalization and offering a better immobilization capacity for Fe, Ni and Zn. The release of metals (Al, Mn, Cu, As, Ba and Pb) was strongly associated with a coupling effect of the physico-chemical factors, with metal-specific responses to curing temperature, curing duration and pH. Mn mobility showed a dramatic sensitivity to ambient pH while Ba was less pH-dependent. Al release is related to strength and leached out by dissolution in all situations considered. Considering that dredged marine sediments may contain multiple metal contaminants which exhibit individual responses to remediation, treatment with GGBS may be considered a potentially suitable management option.

13.
BMC Med Imaging ; 20(1): 47, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375663

RESUMO

BACKGROUND: With the development of three dimensional (3D) reconstruction and printing technology, it has been widely using in the field of urology. However, there have been few studies reporting the role of 3D reconstruction in zero-ischemia partial nephrectomy (PN). The aim of this study was to assess the role of 3D reconstruction and conventional computer tomography angiography (CTA) in zero-ischemia laparoscopic partial nephrectomy (LPN). METHODS: A total of 60 consecutive patients undergoing zero-ischemia LPN between October 2017 and March 2018 who underwent CTA (CTA group including 30 patients) and 3D reconstruction (3D group including the remaining 30 patients) preoperatively were included. 3D reconstruction and CTA images were prepared which were used to demonstrate the number and spatial interrelationships of the location of renal tumors and tumor feeding arteries. These radiological findings were directly correlated with intraoperative surgical findings at laparoscopy. Baseline, perioperative variables and the rate of accurate tumor feeding artery orientation were compared between groups. RESULTS: All LPNs were completed without conversion to renal hilar clamping or open surgery. Preoperative 3D reconstruction identified that 15 patients had only one tumor feeding artery, 12 had two, and another 3 had three, while the conventional CTA revealed that 22 patients had one tumor feeding artery, 8 had two (P > 0.05). The mean operation time was shorter and estimated blood loss was less in the 3D group (P < 0.05) and the rate of accurate tumor feeding artery dissection was higher in the 3D group (91.7%) in comparison with the CTA group (84.2%). The baseline characteristics and renal function outcomes had no statistical differences between groups. CONCLUSIONS: 3D reconstruction can provide comprehensive information for the preoperative evaluation and intraoperative orientation about tumor feeding arteries that may facilitate tumor resection during zero-ischemia LPN for renal tumors.

14.
ACS Appl Mater Interfaces ; 12(21): 23984-23994, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32352277

RESUMO

Although organic-inorganic halide perovskite solar cells (PSCs) have shown dramatically enhanced power conversion efficiencies (PCEs) in the last decade, their long-term stability is still a critical challenge for commercialization. To address this issue, tremendous research efforts have been devoted to exploring all-inorganic PSCs because of their intrinsically high structural stability. Among them, CsPbIBr2-based all-inorganic PSCs have drawn increasing attention owing to their suitable band gap and favorable stability. However, the PCEs of CsPbIBr2-based PSCs are still far from those of their organic-inorganic counterparts, thus inhibiting their practical applications. Herein, we demonstrate that by simply doping an appropriate amount of Cu2+ into a CsPbIBr2 perovskite lattice (0.5 at. % to Pb2+), the perovskite crystallinity and grain size are increased, the perovskite film morphology is improved, the energy level alignment is optimized, and the trap density and charge recombination are reduced. As a consequence, a decent PCE improvement from 7.81 to 10.4% is achieved along with an enhancement ratio of 33% with a CsPbIBr2-based PSC. Furthermore, the long-term stability of CsPbIBr2-based PSCs against moisture and heat also remarkably improved by Cu2+ doping. This work provides a facile and effective route to improve the PCE and long-term stability of CsPbIBr2-based all-inorganic PSCs.

15.
ACS Appl Mater Interfaces ; 12(20): 23340-23346, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32348113

RESUMO

Magnetic nanostructures with conical shape are highly desired for pursuing extraordinary magnetic properties and microwave absorption. However, the fabrication of such nanostructures with controlled shape and size uniformities and alignment is not yet realized. Accordingly, the magnetic properties and their application as microwave absorber are not well understood. Here, we report on the first demonstration of controlled fabrication of soft magnetic nickel nanocone arrays with sharp geometry, large aspect ratio, uniform size, and parallel alignment. The imaginary part of the relative complex permeability shows multiband absorption in the 2-17 GHz range. Such an exceptional microwave absorption results from the uniform conical shape and size and the parallel alignment. The absorption mechanisms are discussed under the framework of natural resonance and exchange resonance. The natural resonance is dependent on the shape anisotropy and facilitated by the conical geometry. The exchange resonance is well explained by the observation of the bulk spin waves with exchange coupling at the tip of nanocones using the inelastic light scattering and is consistent with exchange theory predictions for the quantization of bulk spin waves. We expect that our work will shed light on the physical insights into the magnetic properties of nanocones and find great potential in applications of microwave absorption.

16.
Cell Death Dis ; 11(3): 163, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123166

RESUMO

While B cells in the tumor microenvironment (TME) might play important roles in cancer progression, their impacts on the renal cell carcinoma (RCC) metastasis remained unclear, which drew our attention to further explore. We found that RCC tissues could recruit more B cells than the surrounding normal renal tissues from human clinical RCC samples. Wound healing assay, transwell assay and 3D invasion assays demonstrated that recruited B cells, also known as tumor-educated B cells (TEB), could significantly increase the RCC cell migration and invasion. In addition, in vivo data from xenograft RCC mouse model also confirmed that TEB could enhance RCC cell invasive and metastatic capability. Mechanism dissection revealed that TEB activated IL-1ß/HIF-2α signals in RCC cells that could induce the downstream Notch1 signaling pathway. The above results demonstrated the key roles of TEB within renal cancer associated tumor microenvironment were metastasis-promotor and might help us to develop the potential therapies via targeting these newly identified IL-1ß/HIF-2α/Notch1 signals in RCC progression.

17.
Cancer Med ; 9(5): 1830-1841, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31943867

RESUMO

Cancer susceptibility candidate 9 (CASC9) is a recently identified lncRNA that acted as a tumor promotor in diversified cancer types. However, its role in papillary thyroid cancer (PTC) remains unknown. The expression of CASC9 was measured in 52 human PTC tissues and PTC cell lines as well as their controls. The proliferation, migration, and invasion of PTC cells were determined after knockdown or overexpression of CASC9 to evaluate the effect of CASC9 on PTC cells. Also, the role of PTC tumorigenesis was confirmed in mice xenograft models. Additionally, the underlying mechanisms of CASC9 were further researched. We found that CASC9 expression was augmented in human PTC tissues and cells. Higher CASC9 expression was associated with large tumor size, advanced stage, or lymph node metastasis. Downregulation of CASC9 significantly attenuated the proliferative, migrative, and invasive abilities of PTC cells, and suppressed tumorigenesis in vivo. While overexpression of CASC9 elevated the proliferation, migration, and invasion of PTC cells. miR-488-3p expression was decreased, and ADAM9 level was increased in PTC tissues and cells. CASC9 expression was negatively related to miR-488-3p, but positively associated with ADAM9 expression in PTC tissues. Molecular mechanism analysis revealed that CASC9 functioned via sponging miR-488-3p to regulate ADAM9 expression, followed by activation of EGFR-Akt signaling. In conclusion, lncRNA CASC9 promoted the malignant phenotypes of PTC via modulating miR-488-3p/ADAM9 pathway. This study may provide a novel therapeutic target for the treatment of PTC.

18.
Nanotechnology ; 31(6): 065102, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31645027

RESUMO

Melittin (MEL), the primary active component of bee venom, has recently emerged as a promising cancer chemotherapeutic agent. However, the instability and rapid degradation of MEL is a significant challenge in practical therapeutic applications. In the present study, graphene oxide (GO)-based magnetic nanocomposites (PEG-GO-Fe3O4) were prepared and adopted as the drug delivery vehicles of MEL, and the anticancer effects of PEG-GO-Fe3O4/MEL complexes on human cervical cancer HeLa cells were studied. PEG-GO-Fe3O4 exhibited a series of unique physical and chemical properties resulting in multiple interactions with MEL, and ultimately the release of MEL. In vitro experiments showed that PEG-GO-Fe3O4/MEL not only distinctly enhanced the inhibition effect on HeLa cells, but also induced pore formation in the cell membrane that ultimately led to cell lysis. In this newly developed drug delivery system, PEGylated GO plays the role of a MEL protector while Fe3O4 nanoparticles act as magnetic responders; therefore active MEL can be released over a long period of time (up to 72 h) and maintain its inhibition effect on HeLa cells.

19.
Mol Cell Endocrinol ; 500: 110634, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678422

RESUMO

BACKGROUND: Thyroid cancer is the most common malignant tumor with relatively high incidence and mortality in endocrine system. Research about thyroid cancer-related targets is the basis for the diagnosis of thyroid cancer and the development of new drugs. However, the predictive value of long non-coding RNA (lncRNA) for the diagnosis and prognosis of thyroid cancer is still in the preliminary stage of exploration. Thus, we for the first time investigated the effects and associated regulatory mechanism of lncRNA Forkhead box D3 antisense RNA 1 (FOXD3-AS1) in thyroid cancer in vitro and in vivo. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA FOXD3-AS1 and miR-296-5p. Cell proliferation was detected through colony formation assay. Cell cycle was analyzed through flow cytometry. Cell mobility was valued through transwell invasion assay and wound healing assay. Western blotting was used to examine the expression of proteins related to cell proliferation and cell migration and TGF-ß1/Smads signaling pathway. Luciferase reporter assay was used to verify the targeting relationship between FOXD3-AS1 and miR-296-5p. Tumor xenograft model was established and immunohistochemistry (IHC) was used to examine the expression of Ki67 and VEGF. RESULTS: We found that the expression of lncRNA FOXD3-AS1was upregulated and it had negative correlation with the level of miR-296-5p in thyroid cancer tissues and cells. LncRNA FOXD3-AS1 knockdown effectively suppressed cell proliferation and cell invasion in vitro. Further study revealed that miR-296-5p was a target of lncRNA FOXD3-AS1 and FOXD3-AS1 exerted anti-tumor effect through up-regulating miR-296-5p. Moreover, we found that FOXD3-AS1 knockdown suppressed the aggressive biological behaviors of thyroid cancer through inactivating the TGF-ß1/Smads signaling pathway. Subsequently, the in vivo experiments further verified that the FOXD3-AS1/miR-296-5p axis exerted obvious anti-tumor effect through inhibiting tumor growth and metastasis and the TGF-ß1/Smads signaling pathway was also inactivated in vivo by the inhibition of FOXD3-AS1. CONCLUSION: Inhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-ß1/Smads signaling pathway.


Assuntos
MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/patologia , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Proteínas Smad/metabolismo , Neoplasias da Glândula Tireoide/genética
20.
Toxicol Lett ; 319: 187-196, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756459

RESUMO

The clinical drug-drug interactions mediated by heterotropic activation on cytochrome P450 (CYP450) kinetics, especially CYP3A4, have received wide concern in recent years. Flavonoids, a group of important natural substances with various pharmacological activities, distribute widely among vegetables, fruits and herbs. The frequent and numerous uses of flavonoids may increase the risk of food/herb-drug interactions. However, little is known about activation effects of flavonoids on CYP3A4. The aim of this study was to investigate activation of CYP3A4 by flavonoids, explore the molecular mechanism, and assess the biological effects on dronedarone (DND) induced toxicity. The results showed that flavone, tangeretin, sinensetin and 6-hydroxyflavone increased the cell viability by decreasing DND-induced cytotoxicity. These four flavonoids could activate the metabolism of DND in hamster pharmacokinetics study. Furthermore, both molecular docking and circular dichroism analysis partially illustrated the molecular mechanism of heterotropic activation. Finally, the pharmacophore model suggested B aromatic ring, hydrophobic groups at 7-position and hydrogen bond acceptors at 4-position may play a vital role in activation of flavonoids on CYP3A4. Taken together, our findings would provide useful information for predicting the potential risks of flavonoid-containing food/herb-drug interactions in humans.


Assuntos
Antiarrítmicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Dronedarona/toxicidade , Ativadores de Enzimas/farmacologia , Flavonoides/farmacologia , Animais , Antiarrítmicos/farmacocinética , Dicroísmo Circular , Cricetinae , Dronedarona/farmacocinética , Ativação Enzimática , Interações Ervas-Drogas , Ligação de Hidrogênio , Masculino , Mesocricetus , Modelos Moleculares , Simulação de Acoplamento Molecular
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