Halide Perovskite Inducing Anomalous Nonvolatile Polarization in Poly(vinylidene fluoride)-based Flexible Nanocomposites.

Ferroelectric materials have important applications in transduction, data storage, and nonlinear optics. Inorganic ferroelectrics such as lead zirconate titanate possess large polarization, though they are rigid and brittle. Ferroelectric polymers are light weight and flexible, yet their polarization is low, bottlenecked at 10 µC cm-2. Here we show poly(vinylidene fluoride) nanocomposite with only 0.94% of self-nucleated CH3NH3PbBr3 nanocrystals exhibits anomalously large polarization (~19.6 µC cm-2) while retaining superior stretchability and photoluminance, resulting in unprecedented electromechanical figures of merit among ferroelectrics. Comprehensive analysis suggests the enhancement is accomplished via delicate defect engineering, with field-induced Frenkel pairs in halide perovskite stabilized by the poled ferroelectric polymer through interfacial coupling. The strategy is general, working in poly(vinylidene fluoride-co-hexafluoropropylene) as well, and the nanocomposite is stable. The study thus presents a solution for overcoming the electromechanical dilemma of ferroelectrics while enabling additional optic-activity, ideal for multifunctional flexible electronics applications.

Optical feedback noise-immune cavity-enhanced optical heterodyne molecular spectrometry for sub-Doppler-broadened detection of C2H2: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 202 (2024)10.1364/OL.507004.

Optical feedback noise-immune cavity-enhanced optical heterodyne molecular spectrometry for sub-Doppler-broadened detection of C2H2.

A novel, to the best of our knowledge, noise-immune cavity-enhanced optical heterodyne molecular spectrometry (NICE-OHMS) has been developed, utilizing optical feedback for laser-to-cavity locking with a common distributed-feedback diode laser. The system incorporates active control of the feedback phase and feedforward control of the laser current, allowing for consecutive laser frequency detuning by scanning a piezoelectric transducer (PZT) attached to the cavity. To enhance the fidelity of the spectroscopic signal, wavelength-modulated (wm) NICE-OHMS is implemented. Benefiting from the optical feedback, a modulation frequency of 15 kHz is achieved, surpassing the frequencies typically used in traditional NICE-OHMS setups. Then, the sub-Doppler-broadened wm-NICE-OHMS signal of acetylene at 1.53 µm is observed. A seven-fold improvement in signal to noise ratio has been demonstrated compared to NICE-OHMS alone and a limit of detection of 6.1 × 10-10cm-1 is achieved.

Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1ß production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

Pressure-Induced Modulation of Tin Selenide Properties: A Review.

Tin selenide (SnSe) holds great potential for abundant future applications, due to its exceptional properties and distinctive layered structure, which can be modified using a variety of techniques. One of the many tuning techniques is pressure manipulating using the diamond anvil cell (DAC), which is a very efficient in situ and reversible approach for modulating the structure and physical properties of SnSe. We briefly summarize the advantages and challenges of experimental study using DAC in this review, then introduce the recent progress and achievements of the pressure-induced structure and performance of SnSe, especially including the influence of pressure on its crystal structure and optical, electronic, and thermoelectric properties. The overall goal of the review is to better understand the mechanics underlying pressure-induced phase transitions and to offer suggestions for properly designing a structural pattern to achieve or enhanced novel properties.

Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox-responsive and emissive TPE-ss covalent organic framework (COF) nanocarrier by integrating aggregation-induced emission luminogens and redox-responsive disulfide motifs into the COF skeleton is developed. TPE-ss COF allows for efficient loading and delivery of matrine, a renowned anti-cryptosporidial drug, which significantly reduces MI/R-induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5 min after 30 min of ischemia. Moreover, TPE-ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE-ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE-ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri-reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.

COMMD3 Expression Affects Angiogenesis through the HIF1α/VEGF/NF-κB Signaling Pathway in Hepatocellular Carcinoma In Vitro and In Vivo.

Background: High expression of copper metabolizing MURR1 domain (COMMD3) is significantly correlated with poor prognosis in hepatocellular carcinoma (HCC) patients. Here, we explored the mechanism by which COMMD3 affects HCC angiogenesis through the HIF1α/VEGF/NF-κB signaling pathway. Methods: SK-Hep1 and Hep-3B cell lines were transfected by COMMD3 overexpression and RNA interference lentivirus and verified using RT-qPCR and western blotting techniques. Using RNA sequencing, we analyzed differentially expressed genes in COMMD3-overexpressed and COMMD3-knockdown HCC cells. Altogether, colony formation assay, wound healing assay, transwell cell invasion assay, flow cytometry apoptosis experiments, HUVEC tube formation detection, phalloidin staining assay, western blotting, immunohistochemical staining, and a nude mouse xenograft model were used for experimental verification. Results: Lentivirus COMMD3 overexpression and knockdown were successfully established in HCC cells. COMMD3 overexpression significantly promoted the proliferation, angiogenesis, migration, and invasion capacities of HCC cells with no obvious effect on apoptosis versus controls while COMMD3 knockdown showed the opposite trend. The expression and protein levels of COMMD3 as well as HIF1α, VEGF, and NF-κB were increased in COMMD3-overexpressing HCC cells versus control cells, while they were reduced after COMMD3 knockdown. In addition, RNA-seq indicated that COMMD3 is an indispensable gene for HCC angiogenesis through HIF1α and NF-κB signaling pathways. Conclusion: This study showed that low expression of COMMD3 can inhibit HCC angiogenesis by suppressing the HIF1α/VEGF/NF-κB pathway. This implicates COMMD3 as a potential biomarker for improving the therapeutic outcome of HCC.

Genetic Polymorphisms in CYP2C19 Cause Changes in Plasma Levels and Adverse Reactions to Anlotinib in Chinese Patients With Lung Cancer.

Background: Anlotinib is a small molecular multi-targeting tyrosine kinase inhibitor. Growing evidence indicates that treatment efficacy, and toxicity varies considerably between individuals. Therefore, this study aimed to investigate the relationship between cytochrome P450 (CYP450) gene polymorphisms, drug concentrations, and their adverse reactions in anlotinib-treated patients with lung cancer. Methods: We enrolled 139 patients with lung cancer, treated with anlotinib. Twenty loci in the following five genes of the CYP450 family were genotyped: CYP450 family 3 subfamily A member 5 (CYP3A5), 3 subfamily A member 4 (CYP3A4), 2 subfamily C member 9 (CYP2C9), 2 subfamily C member 19 (CYP2C19), and 1 subfamily A member 2 (CYP1A2). Data on adverse reactions were collected from patients, and plasma anlotinib concentrations were measured. Results: There were significant variances in plasma trough concentration (3.95-52.88 ng/ml) and peak plasma concentration (11.53-42.8 ng/ml) following administration of 8 mg anlotinib. Additionally, there were significant differences in the plasma trough concentration (5.65-81.89 ng/ml) and peak plasma concentration (18.01-107.18 ng/ml) following administration of 12 mg anlotinib. Furthermore, for CYP2C19-rs3814637, the peak plasma concentrations of mutant allele T carriers (TT+CT) were significantly higher than those of wildtypes (CC). For CYP2C19-rs11568732, the peak plasma concentrations of the mutant allele G carriers (GT+GG) were significantly higher than those of the wild-type (TT). More importantly, the incidence rates of hypertension and hemoptysis (peripheral lung cancer) with TT+CT in rs3814637 and GT+GG in rs11568732 were significantly higher than those with CC and TT. Conclusions: The plasma trough and peak concentrations varied significantly for both 8 and 12 mg of anlotinib. Single-nucleotide polymorphisms in CYP2C19 are significantly associated with hypertension, hemoptysis, and anlotinib peak concentrations. Polymorphisms in CYP450 may explain inter-individual differences in anlotinib-related adverse reactions.

Investigating the Association between COMMD3 Expression and the Prognosis of Hepatocellular Carcinoma.

The Copper Metabolism MURR1 Domain (COMMD) family proteins are known to play roles in promoting or inhibiting the proliferation, migration and invasion of tumor cells. However, the role of COMMD3 in hepatocellular carcinoma are still unclear. By investigating the TCGA datasets, we found that the mRNA expression of COMMD3 was significantly upregulated in hepatocellular carcinoma tissue compared with normal liver tissue, which was further supported by Oncomine dataset, Western blot, qRT-PCR, and IHC analysis. Moreover, Kaplan-Meier survival analysis showed that the high expression of COMMD3 was associated with poor overall survival (OS) and disease-free survival (DFS). Consistently, the clinic-pathological analysis found that the overexpression of COMMD3 was correlated with advanced TNM stage, advanced T stage and vascular invasion. By performing multivariate analysis, we found that the expression of COMMD3 was an independent influencing factor on OS and DFS. Furthermore, we knocked down COMMD3 in HCC cells via RNA interference. The results showed that silencing COMMD3 could inhibit the migration, invasion, and angiogenesis of HCC cells. Finally, we established xenograft tumor model in nude mice, and the knockdown of COMMD3 suppressed tumor growth and angiogenesis. In summary, our study showed that the high expression of COMMD3 was correlated with poor prognosis in HCC patients and contributed to migration, invasion and angiogenesis of HCC cells.

Long-term exposure to copper induces mitochondria-mediated apoptosis in mouse hearts.

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage.

Improvement in salt tolerance of Iris pseudacorus L. in constructed wetland by exogenous application of salicylic acid and calcium chloride.

Wetland plants play a major role in the process of wastewater treatment in constructed wetlands (CWs). The inhibitory effect of salt stress on plants may reduce the performance of CWs. In this study, salicylic acid (SA) and/or calcium ion (Ca2+) were used for root pretreatment to alleviate the salt stress in Iris pseudacorus L. The results showed that root pretreatment with SA and/or Ca2+ improved the response of Iris pseudacorus L. to salinity by increasing growth, photosynthetic pigments, Pro content, enzymes activities and K+ content. In addition, SA and/or Ca2+ application in saline conditions decreased the relative conductivity and content of malondialdehyde. RNA-seq analysis showed the expression of hormone signaling genes, potassium ion transporter genes, oxidative stress genes and photosynthesis genes were up-regulated after pretreating with SA and CaCl2. In conclusion, the addition of SA and Ca2+ could improve the saline wastewater treatment efficiency of CWs by enhancing the salt tolerance of Iris pseudacorus L.

Compact high-contrast silicon optical filter using all-passive and CROW Fano nanobeam resonators.

We propose and experimentally demonstrate a high-order coupled-resonator optical waveguide (CROW) nanobeam filter with semi-symmetrical Fano resonance enhancement. Thanks to the tight arrangement of multiple nanobeams and assistance of the partial transmission element, the designed filter has a high-contrast transmission and low insertion loss. Finally, the fabricated filter has a compact size of 20µm×10µm, a high extinction ratio as much as 70 dB, and an insertion loss as low as 1 dB. This filter shows a passive structure without thermal control configuration for calibration on each resonator. This compact filter can be a basic building block for various applications requiring high extinction ratio filtering, such as single-photon source filtering of integrated photon chips.

HIF-1α RNAi Combined with Asparagus Polysaccharide Exerts an Antiangiogenesis Effect on Hepatocellular Carcinoma In Vitro and In Vivo.

BACKGROUND: Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and life-threatening malignancies globally. Hypoxia activates hypoxia-inducible factor-1α (HIF-1α), which is the key factor in promoting angiogenesis in HCC. Currently, there are few studies on the effects of HIF-1α-targeted gene therapy combined with traditional Chinese herbal extracts. OBJECTIVE: We investigated the effects of HIF-1α RNA interference (RNAi) combined with asparagus polysaccharide (ASP) on HCC in vitro and in vivo. METHODS: CCK-8, wound-healing, transwell, and human umbilical vein endothelial cell tube formation assays were performed to evaluate the proliferation, migration, invasion, and angiogenesis of HCC cells in vitro. In addition, western blotting, qPCR, and immunohistochemistry were performed to detect the expression of HIF-1α, vascular endothelial growth factor, AKT, p-AKT, ERK, p-ERK, and CD34 in HCC cells. RESULTS: The combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep1 and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. In addition, this combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways. These results were observed both in vitro and in vivo. CONCLUSION: Our study indicates that HIF-1α RNAi combined with ASP inhibits angiogenesis in HCC via the PI3K and MAPK signaling pathways. Thus, we suggest that this combination may be an effective method for the comprehensive treatment of HCC, which may provide new ideas for the treatment of other malignant tumors.

Asparagus Polysaccharide inhibits the Hypoxia-induced migration, invasion and angiogenesis of Hepatocellular Carcinoma Cells partly through regulating HIF1α/VEGF expression via MAPK and PI3K signaling pathway.

Aim: Although there are so many treatment strategies used for hepatocellular carcinoma (HCC), the overall survival (OS) of HCC patients still remains very low. In our previous studies, asparagus polysaccharide (ASP) has been demonstrated to suppress proliferation, migration, invasion and angiogenesis of HCC cells under normoxic conditions in vitro. However, the inhibitory effects of ASP on the hypoxia-induced migration, invasion and angiogenesis of HCC cells still remain largely unexplored. Materials and methods: Cell Counting Kit-8 (CCK-8) assay, transwell assay, and tube formation assay were used to determine the effects of ASP on hypoxia-induced proliferation, migration, invasion and angiogenesis of HCC cells. ELISA, Western blotting analysis and immunofluorescence assay were used to confirm the effects of ASP on the expressions of HIF-1α and VEGF at the protein level. Moreover, effects of ASP on signaling pathway-related proteins were investigated by Western blotting analysis. Immunohistochemistry (IHC) assay was applied to test the effects of ASP on angiogenesis-associated proteins of tumor cells. Results: We showed that ASP effectively suppressed hypoxia-induced proliferation, migration, invasion and angiogenesis of SK-Hep1 and Hep-3B cells in a dose-dependent manner. In addition, the inhibitory effect of ASP might be partly attributed to down-regulation of HIF1α and VEGF proteins in SK-Hep1 and Hep-3B cells under hypoxic conditions. Moreover, signaling pathway study indicated that ASP significantly down-regulated the hypoxia-induced expressions of p-AKT, p-mTOR and p-ERK, while it had little effects on AKT, mTOR and ERK. Besides, SK-Hep1 xenograft tumor models in nude mice further confirmed that the inhibitory effect of ASP on xenograft tumors might be exerted partly via down-regulation of HIF1α and VEGF through blocking MAPK and PI3K signaling pathways. Conclusions: Our findings suggested that ASP suppressed the hypoxia-induced migration, invasion and angiogenesis of HCC cells partly through regulating HIF-1α/VEGF expression via MAPK and PI3K signaling pathways.

Diagnostic rather than prognostic markers-relationship between EpCAM overexpression and lung cancer: a meta-analysis.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs). However, the diagnostic and prognostic significance of EpCAM in lung cancer remains largely undetermined. In the present study, we systematically summarized and elucidated the correlation between EpCAM overexpression and lung cancer through a meta-analysis. METHODS: Six databases (PubMed, Web of Science, Cochrane Library, and Embase, CnKI and Wanfang Database) were systematically searched. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria were adopted to assess the qualities of the included studies. Relevant data were extracted for meta-analysis using the Stata12.0 software. Unadjusted mixed odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were estimated to evaluate the correlation between EpCAM overexpression and lung cancer. The sensitivity and specificity of the included studies were used to construct the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). RESULTS: A total of 14 studies consisting of 2,658 lung cancer patients were included following the PICOS principle. We found that the EpCAM expression was significantly higher in lung cancer patients compared with normal controls, including patients with benign pulmonary diseases (OR =63.71, 95% CI, 14.59-278.21, P=0.003) and healthy individuals (OR =520.08, 95% CI, 16.38-16,510.80, P=0.002), and its overexpression was negatively associated with the TNM stage (III + IV) (OR =0.41, 95% CI, 0.21-0.82, P=0.073. The combined sensitivity and specificity of EpCAM overexpression in the diagnosis of lung cancer were 0.79 (95% CI, 0.59-0.90) and 0.98 (95% CI, 0.95-0.99), respectively, and the SROC-AUC was 0.98 (95% CI, 0.97-0.99). Multivariate analysis of 322 lung cancer patients showed that there was no significant correlation between the EpCAM overexpression and prognosis of lung cancer (HR =2.28, 95% CI, 0.80-6.51, P=0.002). Deeks' funnel plot analysis showed the existence of publication bias (P=0.000). CONCLUSIONS: Our present findings suggested that EpCAM overexpression was not sensitive enough to predict the prognosis of lung cancer. Moreover, it was also a potential diagnostic indicator for lung cancer and correlated with TNM staging of lung cancer.

Using porphyrins as albumin-binding molecules to enhance antitumor efficacies and reduce systemic toxicities of antimicrobial peptides.

Antimicrobial peptides (AMPs) are originally developed for anti-infective treatments. Because of their membrane-lytic property, AMPs have been considered as candidates of antitumor agents for a long time. However, their antitumor applications are mainly hampered by fast renal clearance and high systemic toxicities. This study proposes a strategy aiming at addressing these two issues by conjugating AMPs with porphyrins, which bind to albumin increasing AMPs' resistance against renal clearance and thus enhancing their antitumor efficacies. Porphyrins' photodynamic properties can further augment AMPs' antitumor effects. In addition, circulating with albumin ameliorates AMPs' systemic toxicities, i.e. hemolysis and organ dysfunctions. As an example, we conjugated an AMP, K6L9, with pyropheophorbide-a (PPA) leading to a conjugate of PPA-K6L9. PPA-K6L9 bound to albumin with a KD value at the sub-micromolar range. Combining computational and experimental approaches, we characterized the molecular interaction of PPA-K6L9 with albumin. Furthermore, PPA-conjugation promoted K6L9' antitumor effects by prolonging its in vivo retention time, and reduced the hemolysis and hepatic injuries, which confirmed our design strategy.

Hamiltonian Hopping for Efficient Chiral Mode Switching in Encircling Exceptional Points.

Dynamically encircling exceptional points (EPs) can lead to chiral mode switching as the system parameters are varied along a path that encircles EP. However, conventional encircling protocols result in low transmittance due to path-dependent losses. Here, we present a paradigm to encircle EPs that includes fast Hamiltonian variations on the parameter boundaries, termed Hamiltonian hopping, enabling ultrahigh-efficiency chiral mode switching. This protocol avoids path-dependent loss and allows us to experimentally demonstrate nearly 90% efficiency at 1550 nm in the clockwise direction, overcoming a long-standing challenge of non-Hermitian optical systems and powering up new opportunities for EP physics.

Ultracompact optical switch using a single semisymmetric Fano nanobeam cavity.

We propose and theoretically analyze a generalized four-port waveguide-cavity system with a novel, to the best of our knowledge, semisymmetric Fano structure. By applying the system to a silicon-based photonic crystal nanobeam cavity (PCNC), we experimentally demonstrate an ultracompact crossbar optical switch with high drop port transmission. A low insertion loss of 1.5 dB in the drop port at the cross state is achieved comparing to the 8.5 dB insertion loss in a traditional non-Fano structure. The device is also benefited by the high quality factor and small mode volume for efficient switching and the ultracompact footprint of $ 14\;\unicode{x00B5} {{\rm m}^2} $14µm2 in the core structure. The proposed PCNC switch shows great potential in various optical systems on chip to increase the integration and reduce energy consumption.

Upregulation of hypoxia-inducible factor 1α mRNA expression was associated with poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: HIF1α mRNA expression in hepatocellular carcinoma (HCC) tissues and its relationship with the prognosis in HCC patients is still unclear. We performed this study to investigate the expression of HIF1α mRNA and its correlation with the prognosis in HCC patients. MATERIALS AND METHODS: GSE14520 and Oncomine database were used to analyse the differential expression of HIF1α mRNA among HCC tissues and corresponding peritumour tissues or normal liver tissues. The relationship between HIF1α mRNA expression and the clinicopathological features and survival in HCC patients was analysed using the GSE14520 dataset. CCK-8 assay, wound-healing assay, transwell invasion assay, tube formation assay, and subcutaneous xenograft tumour assays using nude mice were used to confirm the function of HIF1α. RESULTS: Expression of HIF1α mRNA was significantly upregulated in HCC tissues (P<0.05 in all cases); this was supported by the results of the Western blotting (P=0.031) and IHC analyses. Our analysis of the clinicopathological features of HCC patients indicated that high HIF1α mRNA expression was strongly related with TNM stage III (P=0.002) and BCLC stage C (P=0.038). Survival analysis demonstrated that HCC patients with high HIF1α mRNA expression had a short overall survival (OS) (P=0.048), but showed no significant difference in recurrence-free survival (RFS) (P=0.066) compared to patients with low HIF1α mRNA expression. We further demonstrated that HIF1α promoted the proliferation, migration, invasion, and angiogenic ability of HCC cells, by using the stably transformed SK-Hep1 and Hep-3B cell lines showing HIF1α overexpression. Finally, xenograft tumour models of nude mice showed that RNA interference-mediated HIF1α silencing suppressed tumour growth and angiogenesis in HCC. CONCLUSION: Our study suggests that the upregulation of HIF1α mRNA, which is found in HCC tissues and associated with poor prognosis in HCC patients, contributed to the proliferation, migration, invasion, and angiogenic ability of HCC cells.

Asparagus Polysaccharide Suppresses the Migration, Invasion, and Angiogenesis of Hepatocellular Carcinoma Cells Partly by Targeting the HIF-1α/VEGF Signalling Pathway In Vitro.

Hypoxia-inducible factor-1α (HIF-1α) plays a key role by triggering the transcriptional activation of a number of genes involved in migration, invasion, and angiogenesis in hepatocellular carcinoma (HCC). Thus, suppressing tumour growth by targeting the HIF-1α/VEGF signalling pathway represents a promising strategy for the treatment of HCC. In our previous studies, we found that asparagus polysaccharide (ASP) suppressed the proliferation and promoted the apoptosis of HCC cells both in vivo and in vitro. To further explore the potential mechanisms of the antitumor effects of ASP in HCC, we investigated effects of ASP on the migration, invasion, and angiogenesis of HCC cells (SK-Hep1 and Hep-3B) using an in vitro experimental model. First, we found that ASP effectively suppressed the proliferation of the SK-Hep1 and Hep-3B cells but did not cause significant cytotoxicity in normal liver cells (L-O2). Then, we found that ASP inhibited the migration and invasion of the SK-Hep1 and Hep-3B cells and HCC cells-induced angiogenesis of human umbilical vein endothelial cells in a concentration-dependent manner. Mechanistic studies revealed that the inhibition of migration, invasion, and angiogenesis by ASP in the SK-Hep1 and Hep-3B cells might occur via the downregulation of HIF-1α/VEGF signalling pathway. Finally, our results also showed that the inhibition of HIF-1α by ASP may be mediated through the downregulation of the phosphorylation levels of AKT, mTOR, and ERK. In conclusion, our results suggest that ASP suppresses the migration, invasion, and angiogenesis of HCC cells partly via inhibiting the HIF-1α/VEGF signalling pathway.