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BACKGROUND: The need for intraoperative endoscopic nasobiliary drainage during laparoscopic cholecystectomy and laparoscopic common bile duct exploration with primary closure is controversial in the treatment of cholecystolithiasis combined with choledocholithiasis. The aim of this study was to evaluate the safety and efficacy of laparoscopic cholecystectomy + laparoscopic common bile duct exploration + intraoperative endoscopic nasobiliary drainage + primary closure (LC + LCBDE + IO-ENBD + PC). The safety of different intubation methods in IO-ENBD was also evaluated. METHOD: From January 2018 to January 2022, 168 consecutive patients with cholecystolithiasis combined with choledocholithiasis underwent surgical treatment in our institution. Patients were divided into two groups: group A (n = 96) underwent LC + LCBDE + IO-ENBD + PC and group B (n = 72) underwent LC + LCBDE + PC. Patient characteristics, perioperative indicators, complications, stone residual, and recurrence rates were analyzed. Group A was divided into two subgroups. In group A1, the nasobiliary drainage tube was placed in an anterograde way, and in group A2, nasobiliary drainage tube was placed in an anterograde-retrograde way. Perioperative indicators and complications were analyzed between subgroups. RESULTS: No mortality in the two groups. The operation success rates in groups A and B were 97.9% (94/96) and 100% (72/72), respectively. In group A, two patients were converted to T-tube drainage. The stone clearance rates of group A and group B were 100% (96/96) and 98.6% (71/72), respectively. Common bile duct diameter was smaller in group A [10 vs. 12 mm, P < 0.001] in baseline data. In perioperative indicators, group A had a longer operation time [165 vs.135 min, P < 0.001], but group A had a shorter hospitalization time [10 vs.13 days, P = 0.002]. The overall complications were 7.3% (7/96) in group A and 12.5% (9/72) in group B. Postoperative bile leakage was less in group A [0% (0/96) vs. 5.6% (4/72), P = 0.032)]. There were no residual and recurrent stones in group A. And there were one residual stone and one recurrent stone in group B (all 1.4%). The median follow-up time was 12 months in group A and 6 months in group B. During the follow-up period, 2 (2.8%) patients in group B had a mild biliary stricture. At subgroup analysis, group A1 had shorter operation time [150 vs. 182.5 min, P < 0.001], shorter hospitalization time [9 vs. 10 days, P = 0.002], and fewer patients with postoperative elevated pancreatic enzymes [32.6% (15/46) vs. 68% (34/50), P = 0.001]. CONCLUSION: LC + LCBDE + IO-ENBD + PC is safer and more effective than LC + LCBDE + PC because it reduces hospitalization time and avoids postoperative bile leakage. In the IO-ENBD procedure, the antegrade placement of the nasobiliary drainage tube is more feasible and effective because it reduces the operation time and hospitalization time, and also reduces injury to the duodenal papilla.
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Colecistectomia Laparoscópica , Colecistolitíase , Coledocolitíase , Laparoscopia , Humanos , Coledocolitíase/complicações , Coledocolitíase/cirurgia , Colecistolitíase/complicações , Colecistolitíase/cirurgia , Ducto Colédoco/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Drenagem/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Colangiopancreatografia Retrógrada Endoscópica/métodosRESUMO
Precisely aligned optical components are crucial prerequisites for X-ray tomography at high resolution. We propose a device with a fractal pattern for precise automatic focusing. The device is etched in a Si substrate by deep reactive ion etching and then filled by a self-terminating bottom-up Au electroplating process. The fractal nature of the device produces an X-ray transmission image with globally homogeneous macroscopic visibility and high local contrast for pixel sizes in the range of 0.165 µm to 11 µm, while the high absorption contrast provided between Au and Si enables its use for X-ray energies ranging from 12 keV to 40 keV.
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The orientation mismatch between the cone beam of an X-ray tube and the grating lines in a flat substrate remains a big challenge for laboratory grating-based X-ray interferometry, since it severely limits the imaging field of view. Here, we fabricated fan-shaped G0 source gratings by modulating the electric field during the deep reactive ion etching of silicon. The gold electroplated fan-shaped G0 grating (3.0 µm pitch) in a 20 keV interferometer improves the uniformity of the field of view with an increase of average visibility from 16.2% to 18.5% and a better angular sensitivity (by a factor 5.8) at the edges.
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Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.
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Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Redes e Vias Metabólicas/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients. Dlg5-silencing promoted epithelial-mesenchymal transition, invadopodium formation, gelatin degradation function, and invadopodium-associated invasion of HepG2 cells. In contrast, Dlg5 overexpression inhibited epithelial-mesenchymal transition, functional invadopodium formation, and invasion of SK-Hep1 cells. Both Girdin and Tks5, but not the Tks5 nonphosphorylatable mutant, were responsible for the enhanced invadopodium formation and invasion of Dlg5-silenced HepG2 cells. Furthermore, Dlg5 interacted with Girdin and interfered with the interaction of Girdin and Tks5. Dlg5 silencing promoted Girdin and Tks5 phosphorylation, which was abrogated by Girdin silencing and rescued by inducing shRNA-resistant Girdin expression. Moreover, Dlg5 overexpression significantly inhibited HCC intrahepatic and lung metastasis in vivo. Taken together, our data indicate that Dlg5 acts as a novel regulator of invadopodium-associated invasion via Girdin and by interfering with the interaction between Girdin and Tks5, which might be important for Tks5 phosphorylation in HCC cells. Conceivably, Dlg5 may act as a new biomarker for prognosis of HCC patients.
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Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Podossomos/fisiologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , FosforilaçãoRESUMO
Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling.
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Antineoplásicos Fitogênicos/farmacologia , Apigenina/farmacologia , Glucuronatos/farmacologia , Proteínas dos Microfilamentos/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Proteínas de Transporte Vesicular/antagonistas & inibidores , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos , Células Hep G2/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas dos Microfilamentos/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Histidine triad nucleotide-binding protein 1 (Hint1) is a haploinsufficient tumor suppressor gene. Its role in cancer cell migration has not been previously speculated. In the current study, we examined the expression of Hint1 in metastatic and non-metastatic lymph nodes of hepatocellular carcinoma (HCC) patients and further elucidated the effect of Hint1 expression on girdin expression and phosphorylation of AKT and ERK1/2 and on the migration of HCC cells in vitro. Expression of Hint1 and girdin in primary HCC tissues and metastatic and non-metastatic lymph nodes was determined by RT-PCR assays. HepG2 cells were transfected with plasmid vectors overexpressing Hint1 or small interfering RNA (siRNA) targeting Hint1, girdin, Hint1 plus girdin, or the scrambled RNA. Migration and invasion of HCC cells were examined by wound and Transwell assays. Protein expression was detected by immunofluorescence and immunoblotting assays. RT-PCR assays revealed that the messenger RNA (mRNA) transcript levels of Hint1 were markedly lower than those of primary HCC tissues and non-metastatic lymph nodes (P < 0.01). By contrast, the mRNA transcript levels of girdin were significantly higher than non-metastatic lymph nodes (P < 0.05). Furthermore, siRNA knockdown of HINT1 resulted in a significant increase in the mRNA transcript levels of girdin in HepG2 cells (P < 0.05). Wound assays and Transwell assays showed that Hint1 knockdown by siRNA significantly enhanced the migration and invasion of HepG2 cells compared to HepG2 cells transfected with scrambled siRNA. Hint1 knockdown also led to significantly increased phosphorylation of girdin and AKT in HepG2 cells (P < 0.05), which, however, was effectively aborted by girdin knockdown by siRNA (P < 0.05). Hint1 is downregulated in metastatic lymph nodes and is implicated in migration and invasion of HCC cells in vitro by modulating girdin and AKT expression and phosphorylation. The Hint1-girdin-AKT signaling axis should be further dissected for its role in HCC migration and invasion and may be therapeutically targeted to suppress tumor growth and metastasis.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/secundário , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Técnicas In Vitro , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Metástase Linfática , Masculino , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/genética , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas , Proteínas de Transporte Vesicular/genéticaRESUMO
BACKGROUND AND AIM: There is increasing evidence that histidine triad nucleotide-binding protein 1 (HINT1) is a novel tumor suppressor. In the present study, we investigated the mechanism by which HINT1 promotes the stability of inhibitor of NF-κB α (IκBα) in the cytoplasm of hepatocellular carcinoma (HCC) cells, which was observed in our previous study (Wang et al. in Int J Cancer 124:1526-1534, 2009). METHODS: We examined HINT1 and IκBα expression in HCC cell lines and determined the effect of HINT1 overexpression and knockdown on IκBα protein and mRNA expression in these cell lines. Then, ubiquitination assays were performed to investigate the effects of HINT1 expression plasmid transfection on IκBα ubiquitination. Next, the interaction between HINT1 and ß-TrCP was investigated in immunoprecipitation and immunofluorescence assays. RESULTS: Our data showed that increased HINT1 expression in HepG2 and SMMC7702 cells markedly increased IκBα protein levels, while decreased HINT1 expression markedly decreased them. Overexpression or knockdown of HINT1 did not alter the transcription of IκBα, but HINT1 inhibited proteasomal IκBα degradation and reduced its ubiquitination levels. This inhibition might occur because HINT1 is a component of the SCF(ß-TrCP) E3 ligase, which is responsible for IκBα ubiquitination and degradation. CONCLUSION: This study provides new evidence that HINT1 is a regulator of IκBα through SCF(ß-TrCP) E3 ligase. These findings help to clarify the mechanism underlying the anticancer effects of HINT1.
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Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas I-kappa B/genética , Neoplasias Hepáticas/genética , Proteínas do Tecido Nervoso/genética , Proteínas Contendo Repetições de beta-Transducina/genética , Western Blotting , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Células HEK293 , Células Hep G2 , Humanos , Proteínas I-kappa B/metabolismo , Neoplasias Hepáticas/metabolismo , Inibidor de NF-kappaB alfa , Proteínas do Tecido Nervoso/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Ativação Transcricional , Ubiquitinação , Regulação para Cima , Proteínas Contendo Repetições de beta-Transducina/metabolismoRESUMO
The multi-scale characterization of building materials is necessary to understand complex mechanical processes, with the goal of developing new more sustainable materials. To that end, imaging methods are often used in materials science to characterize the microscale. However, these methods compromise the volume of interest to achieve a higher resolution. Dark-field (DF) contrast imaging is being investigated to characterize building materials in length scales smaller than the resolution of the imaging system, allowing a direct comparison of features in the nano-scale range and overcoming the scale limitations of the established characterization methods. This work extends the implementation of a dual-phase X-ray grating interferometer (DP-XGI) for DF imaging in a lab-based setup. The interferometer was developed to operate at two different design energies of 22.0 keV and 40.8 keV and was designed to characterize nanoscale-size features in millimeter-sized material samples. The good performance of the interferometer in the low energy range (LER) is demonstrated by the DF retrieval of natural wood samples. In addition, a high energy range (HER) configuration is proposed, resulting in higher mean visibility and good sensitivity over a wider range of correlation lengths in the nanoscale range. Its potential for the characterization of mineral building materials is illustrated by the DF imaging of a Ketton limestone. Additionally, the capability of the DP-XGI to differentiate features in the nanoscale range is proven with the dark-field of Silica nanoparticles at different correlation lengths of calibrated sizes of 106 nm, 261 nm, and 507 nm.
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Respiratory diseases are one of the most common causes of death, and their early detection is crucial for prompt treatment. X-ray dark-field radiography (XDFR) is a promising tool to image objects with unresolved micro-structures such as lungs. Using Talbot-Lau XDFR, we imaged inflated porcine lungs together with Polymethylmethacrylat (PMMA) microspheres (in air) of diameter sizes between 20 and 500 [Formula: see text] over an autocorrelation range of 0.8-5.2 [Formula: see text]. The results indicate that the dark-field extinction coefficient of porcine lungs is similar to that of densely-packed PMMA spheres with diameter of [Formula: see text], which is approximately the mean alveolar structure size. We evaluated that, in our case, the autocorrelation length would have to be limited to [Formula: see text] in order to image [Formula: see text]-thick lung tissue without critical visibility reduction (signal saturation). We identify the autocorrelation length to be the critical parameter of an interferometer that allows to avoid signal saturation in clinical lung dark-field imaging.
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Pulmão , Polimetil Metacrilato , Animais , Suínos , Pulmão/diagnóstico por imagem , Radiografia , Raios XRESUMO
Background: The mRNA vaccine has become a promising platform for cancer therapy. Lots of studies have been focusing on discovering novel potent cancer-associated antigens to develop mRNA vaccines against cancers. Besides, immunotyping shows the immune status, and immune microenvironment of immunotyping is related with therapeutic reaction. However, potential antigens for mRNA vaccines and immunotyping of liver hepatocellular carcinoma (LIHC) remain far from being understood. Methods: In this study, we collected gene expression data and clinical information data from ICGC and TCGA databases. Using GEPIA2, we calculated differential expression genes and prognostic indices. We applied TIMER to calculate the correlation coefficient between immune infiltrating cells and each gene. Consensus cluster was used for immunotyping of LIHC. Results: We uncovered four most potential candidates including PES1, MCM3, PPM1G, and KPNA2, which were all related with antigen-presenting cell (APC) infiltration and poor survival in LIHC in two independent datasets. Furthermore, three immune-related subtypes (IS1-IS3) of LIHC were identified. All these results were validated in two independent datasets. Furthermore, we validated our results in vitro. Conclusions: The above candidates will be expected to be potential antigen genes for developing anti-LIHC mRNA vaccine, and furthermore, patients with IS2 and IS3 tumors are supposed to be appropriate for mRNA vaccine in LIHC.
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Microstructural information over an entire sample is important to understand the macroscopic behaviour of materials. X-ray scattering tensor tomography facilitates the investigation of the microstructural organisation in statistically large sample volumes. However, established acquisition protocols based on scanning small-angle X-ray scattering and X-ray grating interferometry inherently require long scan times even with highly brilliant X-ray sources. Recent developments in X-ray diffractive optics towards circular pattern arrays enable fast single-shot acquisition of the sample scattering properties with 2D omnidirectional sensitivity. X-ray scattering tensor tomography with the use of this circular grating array has been demonstrated. We propose here simple yet inherently rapid acquisition protocols for X-ray scattering tensor tomography leveraging on these new optical elements. Results from both simulation and experimental data, supported by a null space analysis, suggest that the proposed acquisition protocols are not only rapid but also corroborate that sufficient information for the accurate volumetric reconstruction of the scattering properties is provided. The proposed acquisition protocols will build the basis for rapid inspection and/or time-resolved tensor tomography of the microstructural organisation over an extended field of view.
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We present a method to produce small pitch gratings for X-ray interferometric imaging applications, allowing the phase sensitivity to be increased and/or the length of the laboratory setup to be minimized. The method is based on fabrication of high aspect ratio silicon microstructures using deep reactive ion etching (Bosch technique) of dense grating arrays and followed by conformal electroplating of Au. We demonstrated that low resistivity Si substrates (<0.01 Ohm·cm) enable the metal seeding layer deposition step to be avoided, which is normally required to initiate the electroplating process. Etching conditions were optimized to realize Si recess structures with a slight bottom tapering, which ensured the void-free Au filling of the trenches. Vapor HF was used to remove the native oxide layer from the Si grating surface prior to electroplating in the cyanide-based Au electrolyte. Fabrication of Au gratings with pitch in the range 1.2-3.0 µm was successfully realized. A substantial improved aspect ratio of 45:1 for a pitch size of 1.2 µm was achieved with respect to the prior art on 4-inch wafer-based technology. The fabricated Au gratings were tested with X-ray interferometers in Talbot-Laue configuration with measured visibility of 13% at an X-ray design energy of 26 keV.
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This study aimed to investigate the value of multidisciplinary team (MDT) management in minimally invasive treatment of complex intrahepatic bile duct stones (IHDs) by laparoscopy, choledochoscopy and percutaneous choledochoscopy. The characteristics, perioperative index, complication rate and minimally invasive rate of patients in MDT group (n = 75) and non-MDT group (n = 70) were compared. The members of MDT include doctors in ultrasound, imaging, hepatobiliary and pancreatic surgery, anaesthesia and intensive care medicine. The results showed that minimally invasive surgery reduced the incidence of postoperative residual stones, OR (95% CI) = 0.365 (0.141-0.940) (p = 0.037). MDT reduced the operation time, OR (95% CI) = 0.406 (0.207-0.796) (p = 0.009). Minimally invasive surgery significantly reduced intraoperative bleeding, OR (95% CI) = 0.267 (0.133-0.534) (p < 0.001). Minimally invasive surgery also reduced hospitalization time, OR (95% CI) = 0.295 (0.142-0.611) (p = 0.001). The stone clearance rates of MDT group and non-MDT group were 81.33% and 81.43% respectively. In the MDT group, the operative time was less than that in the non-MDT group (p = 0.010); the intraoperative bleeding volume was significantly less than that in the non-MDT group (p < 0.001); the hospitalization time was less than that in the non-MDT group (p = 0.001). Minimally invasive operation rate:48 cases (64.00%) in MDT group were significantly higher than 17 cases (24.29%) in non-MDT group (p < 0.001). In conclusion, minimally invasive procedures can be selected more through MDT. MDT can shorten the operation time, and minimally invasive surgery can reduce the incidence of residual stones, reduce intraoperative bleeding, and may shorten hospital stay. Therefore, MDT management model can provide personalized and minimally invasive surgical protocol for patients with complex IHD, which has high application value.
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Colelitíase/cirurgia , Endoscopia do Sistema Digestório/métodos , Laparoscopia/métodos , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Colelitíase/diagnóstico , Endoscopia do Sistema Digestório/efeitos adversos , Feminino , Seguimentos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The key optical components of X-ray grating interferometry are gratings, whose profile requirements play the most critical role in acquiring high quality images. The difficulty of etching grating lines with high aspect ratios when the pitch is in the range of a few micrometers has greatly limited imaging applications based on X-ray grating interferometry. A high etching rate with low aspect ratio dependence is crucial for higher X-ray energy applications and good profile control by deep reactive ion etching of grating patterns. To achieve this goal, a modified Coburn-Winters model was applied in order to study the influence of key etching parameters, such as chamber pressure and etching power. The recipe for deep reactive ion etching was carefully fine-tuned based on the experimental results. Silicon gratings with an area of 70 × 70 mm2, pitch size of 1.2 and 2 µm were fabricated using the optimized process with aspect ratio α of ~67 and 77, respectively.
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Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM's impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/ß-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/ß-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Glucosídeos Iridoides/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas/metabolismo , Pironas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Glucosídeos Iridoides/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pironas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
It was previously demonstrated that the long non-coding RNA (lncRNA) small NF90-associated RNA (snaR) served an oncogenic role in human colon cancer, although its roles in other types of cancer remain unknown. To investigate the potential involvement of lncRNA snaR in hepatocellular carcinoma (HCC), expression of snaR in liver biopsies and plasma of patients with HCC and healthy controls was detected by reverse transcription-quantitative polymerase chain reaction. ELISA was used to determine the protein expression levels of transforming growth factor-ß1 (TGF-ß1). A snaR expression vector was transfected into HCC cells, and the effects on cell migration and invasion were analyzed by Transwell migration and Matrigel invasion assays, respectively. The protein expression levels of TGF-ß1 in HCC cells were detected by western blotting. The expression of snaR and TGF-ß1 was significantly increased in the patients with HCC compared with the healthy controls. The plasma expression levels of snaR and TGF-ß1 were positively correlated in patients with HCC; however, not in healthy controls. snaR overexpression significantly promoted cancer cell migration and invasion, and additionally increased TGF-ß1 expression. Treatment with TGF-ß1 did not significantly affect snaR expression. A TGF-ß1 inhibitor attenuated the effects of snaR overexpression in cancer cell migration and invasion. snaR may promote the metastasis of liver cancer through TGF-ß1.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with a high degree of malignancy and recurrence. The influence of the ceRNA network in tumor on the biological function of liver cancer is very important, It has been reported that many lncRNA play a key role in liver cancer development. In our study, integrated data analysis revealed potential eight novel lncRNA biomarkers in hepatocellular carcinoma. METHODS: Transcriptome data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal. Weighted gene co-expression network analysis was performed to identify the expression pattern of genes in liver cancer. Then, the ceRNA network was constructed using transcriptome data. RESULTS: The integrated analysis of miRNA and RNAseq in the database show eight novel lncRNAs that may be involved in important biological pathways, including TNM and disease development in liver cancer. We performed function enrichment analysis of mRNAs affected by these lncRNAs. CONCLUSIONS: By identifying the ceRNA network and the lncRNAs that affect liver cancer, we showed that eight novel lncRNAs play an important role in the development and progress of liver cancer.
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Aim: To explore gene expression profiling in hepatocellular carcinoma (HCC) cells exposed to swertiamarin. Methods: Cell viability, apoptosis and invasion were examined in HepG2 cells after swertiamarin treatment. Tumor growth of SK-Hep-1 cells xenografted in nude mice was monitored after swertiamarin treatment. Total RNA was isolated from HepG2 cells treated with swertiamarin for microarray analysis. The data of microarray were analyzed by bioinformatics. Results: Swertiamarin treatment decreased the viability and invasion while increased the apoptosis of HepG2 cells, and significantly inhibited the growth of SK-Hep-1 cells xenografted in nude mice. Pathway and biological process analysis of differentially expressed genes (DEGs) in swertiamarin treated HepG2 cells showed that PI3k-Akt was the most significant regulated pathway. 47 targets of swertiamarin were predicted by CGBVS while 21 targets were predicted by 3NN. Notably, 8 targets were predicted as the targets of swertiamarin by both programs, including two prominent targets JUN and STAT3. A large range of DEGs induced by swertiamarin could be regulated by JUN and STAT3. Conclusion: Swertiamarin treatment led to significant changes in the expression of a variety of genes that modulate cell survival, cell cycle progression, apoptosis, and invasion. Moreover, most of these genes can be clustered into pathway networks such as PI3K, JUN, STAT3, which are predicted targets of swertiamarin. Further confirmation of these targets will reveal the anti-tumor mechanisms of swertiamarin and facilitate the development of swertiamarin as a novel agent for cancer prevention and treatment.