[Retracted] Celastrus orbiculatus extracts induce apoptosis and inhibit invasion by targeting the maspin gene in human gastric adenocarcinoma cells.

[This retracts the article DOI: 10.3892/ol.2017.7341.].

Composite of g-C3N4/ZnIn2S4 for efficient adsorption and visible light photocatalytic reduction of Cr(VI).

In this paper, the g-C3N4/ZnIn2S4 composite was synthesized by a two-stage hydrothermal method. The microstructure, surface, and optical properties of the composite were thoroughly characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) surface area analysis, and UV-Vis absorption spectroscopic analysis. The removal capacity of Cr(VI) was optimized by using ZnIn2S4 loaded in the composite. Meanwhile, the optimal pH environment for the reduction of Cr(VI) was determined to be about pH 3, and the reduction efficiency could reach more than 99% within 60 min. Further, the results of UV-Vis absorption analysis indicated the high and wide range of light absorption by composite compared with pure g-C3N4. Therefore, the enhanced photocatalytic performance of the composite could be attributed to the well-matched energy band structure between g-C3N4 and ZnIn2S4, which apparently promoted the effective separation and transfer of photogenerated carriers. In addition, the composite showed good stability in the visible light catalytic reaction, and the possible mechanism of the photocatalytic activity of Cr(VI) reduction by the composite was proposed.

Clinical significance of ERBB2 exon 16 skipping: analysis of a real-world retrospective observational cohort study.

BACKGROUND: ERBB2 exon 16 skipping is an alternatively spliced isoform of ERBB2, which was reported to lead to oncogenic activation of ERBB2 and could potentially cause tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) in case studies. In this study, we aimed to evaluate the frequency of ERBB2 exon 16 skipping in a large patient cohort and its function in cancer development. METHODS: A total of 38 680 Chinese patients with cancer whose tumour specimens and/or circulating cell-free DNA underwent targeted nextgeneration sequencing of cancer-related genes were retrospectively reviewed. Clinicopathological features and treatment history of patients harbouring ERBB2 exon 16 skipping were evaluated. RNA-sequencing was performed to validate the presence of exon 16 skipping in ERBB2 at the transcriptional level. RESULTS: ERBB2 exon 16 skipping is rare and was identified in a total of 18 patients (0.046% of total patients), including 12 lung cancers, which were caused by large fragment deletion spanning the whole or partial region of exon 16 (13/18, 72.2%) and/or splice site variants (6/18, 33.3%). The majority of these variants have not been previously reported and three of them were confirmed by RNA-sequencing. Among the 12 patients with lung cancer, 9 had coexisting activating EGFR mutations (exon 19 deletions or L858R) and received prior-treatment with epidermal growth factor receptor TKIs. Further analysis of matched pre-treatment and post-treatment samples in three EGFR-mutated NSCLC patients confirmed that ERBB2 exon 16 skipping was newly acquired on resistance to TKI therapies. In 6 out of 18 patients, including colorectal, gastric and ovarian cancers, there were no mutations in known cancer driver genes detected, indicating that ERBB2 exon 16 skipping might be the oncogenic driver in these patients. CONCLUSIONS: Our data suggest that ERBB2 exon 16 skipping is another mechanism of TKI resistance in EGFR-mutated patients with lung cancer, in addition to its role of being an oncogenic driver in other solid malignancies.

A spectroscopic and theoretical investigation of interaction mechanisms of tetracycline and polystyrene nanospheres under different conditions.

Interaction mechanisms of tetracycline (TC, as a typical antibiotic) on polystyrene microsphere (PSs, as a typical nanoplastic) were conducted by the batch, spectroscopic and theoretical techniques. The batch results showed that Na+ and K+ had no obvious effects on TC adsorption towards PSs, whereas Mg2+ significantly inhibited TC adsorption at pH > 5.0 due to its induced aggregations of PSs. The maximum TC adsorption capacity of PSs in the presence of humic acid (50.99 mg/g) was higher than that of PSs (44.77 mg/g) at pH 6.0. The highly effective adsorption was attributed to electrostatic attraction, π-π interaction and hydrophobic effect, which was determined by FT-IR and XPS analysis. According to DFT (density functional theory) calculations, the adsorption energy of TC/TC+ on PSs (1.52 eV) was significantly higher than that of negative TC- (0.57 eV), whereas minimum distance of TC on PSs (3.684 Å) was shorter than that of TC- on PSs (3.988 Å). The results of theoretical calculations indicated that TC was more preferably adsorbed on PSs with more stable configuration compared to TC-. These findings indicated that PSs can be used as a promising adsorbent for immobilization and pre-concentration of TC from aqueous solutions.

Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells.

OBJECTIVE: To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms. METHODS: The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively. RESULTS: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells. CONCLUSIONS: COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Influence of carbonate on sequestration of U(VI) on perovskite.

Cubic perovskite (CaTiO3) was successfully synthesized by a facile solvothermal method and was utilized to sequestrate U(VI) from aqueous solutions. The batch experiments revealed that carbonate inhibited U(VI) sequestration at pH > 6.0 due to the formation of uranyl-carbonate complexes. The maximum sequestration capacity of U(VI) on perovskite was 119.3 mg/g (pH 5.5). The sequestration mechanism of U(VI) on perovskite were investigated by XPS and EXAFS techniques. According to XPS analysis, the presence of U(IV) and U(VI) oxidation states revealed the photocatalytic reduction of U(VI) by perovskite under UV-vis irradiation. In addition, photocatalytic reduction performance significantly decreased in the presence of carbonate. Based on EXAFS analysis, the occurrence of U-Ti and U-U shells revealed the inner-sphere surface complexation and reductive precipitation of U(VI) on perovskite. These findings herein are crucial for the application of perovskite-based composites in the decontamination of U(VI) in aquatic environmental cleanup.

Mechanistic insights into sequestration of U(VI) toward magnetic biochar: Batch, XPS and EXAFS techniques.

The magnetic iron oxide (Fe3O4) nanoparticles stabilized on the biochar were synthesized by fast pyrolysis of Fe(II)-loaded hydrophyte biomass under N2 conditions. The batch experiments showed that magnetic biochar presented a large removal capacity (54.35mg/g) at pH3.0 and 293K. The reductive co-precipitation of U(VI) to U(IV) by magnetic biochar was demonstrated according to X-ray diffraction, X-ray photoelectron spectroscopy and X-ray absorption near edge structure analysis. According to extended X-ray absorption fine structure analysis, the occurrence of U-Fe and U-U shells indicated that high effective removal of uranium was primarily inner-sphere coordination and then reductive co-precipitation at low pH. These observations provided the further understanding of uranium removal by magnetic materials in environmental remediation.

Impact of water chemistry on surface charge and aggregation of polystyrene microspheres suspensions.

The discharge of microplastics into aquatic environment poses the potential threat to the hydrocoles and human health. The fate and transport of microplastics in aqueous solutions are significantly influenced by water chemistry. In this study, the effect of water chemistry (i.e., pH, foreign salts and humic acid) on the surface charge and aggregation of polystyrene microsphere in aqueous solutions was conducted by batch, zeta potentials, hydrodynamic diameters, FT-IR and XPS analysis. Compared to Na+ and K+, the lower negative zeta potentials and larger hydrodynamic diameters of polystyrene microspheres after introduction of Mg2+ were observed within a wide range of pH (2.0-11.0) and ionic strength (IS, 0.01-500mmol/L). No effect of Cl-, HCO3- and SO42- on the zeta potentials and hydrodynamic diameters of polystyrene microspheres was observed at low IS concentrations (<5mmol/L), whereas the zeta potentials and hydrodynamic diameters of polystyrene microspheres after addition of SO42- were higher than that of Cl- and HCO3- at high IS concentrations (>10mmol/L). The zeta potentials of polystyrene microspheres after HA addition were decreased at pH2.0-11.0, whereas the lower hydrodynamic diameters were observed at pH<4.0. According to FT-IR and XPS analysis, the change in surface properties of polystyrene microspheres after addition of hydrated Mg2+ and HA was attributed to surface electrostatic and/or steric repulsions. These investigations are crucial for understanding the effect of water chemistry on colloidal stability of microplastics in aquatic environment.

Celastrus orbiculatus extracts induce apoptosis and inhibit invasion by targeting the maspin gene in human gastric adenocarcinoma cells.

Celastrus orbiculatus Thunb. has been used as a remedy against cancer and inflammatory diseases for thousands of years in China. Maspin is expressed in normal cells and downregulated in prostate tumor cells. The underlying mechanisms between C. orbiculatus extract (COE) and maspin remain unclear. In the present study, 3 target-specific 19-25 nucleotide maspin small interfering RNAs were designed and synthesized to knockdown maspin expression. The effects of COE on MGC-803/maspin- cell proliferation were evaluated by the MTT assay. Apoptosis was measured by flow cytometry. Invasive activity was measured with the Transwell assay and the associated molecular mechanisms were assessed by western blot analysis. The results demonstrated that COE significantly promoted the expression of maspin (P<0.01) to induce apoptosis and inhibit invasion and migration in MGC803 cells. The expression levels of phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK), phospho-extracellular regulated protein kinase (Erk), B cell lymphoma-2-associated X protein and caspase-3 were increased in the MGC-803/maspin- cells in a dose-dependent manner. The Erk, B-cell lymphoma 2, p-Akt, Akt and p-mechanistic target of rapamycin (mTOR) protein in MGC-803/maspin- cells were reduced in a dose-dependent manner. This indicated that COE may inhibit invasion and migration through phosphoinositide 3-kinase/Akt/mTOR and MAPK signaling pathways in MGC-803/maspin- cells. In conclusion, COE has the ability to improve the expression of maspin to induce apoptosis and inhibit invasion and migration in human gastric adenocarcinoma cells.

The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome.

Tandem pH domain-containing proteins TAPP1 and TAPP2 are adaptor proteins that specifically bind to phosphatidylinositol-3,4-bisphosphate, or PI(3,4)P2, a product of phosphoinositide 3-kinases (PI3K). Although PI3K enzymes have multiple functions in cell biology, including cell migration, the functions of PI (3, 4) P2 and its binding proteins are not well understood. Previously studies found that TAPP2 is highly expressed in primary leukemic B cells that have strong migratory capacity. However, the function and underlying mechanisms of TAPP2 in ESCC remain largely unknown. In the present study, we investigated the level of TAPP2 in human esophageal squamous cell carcinoma (ESCC) tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and western blot analyses. TAPP2 protein level was increased in ESCC tissues compared with corresponding adjacent non-tumor tissues. In vitro experiments showed that under-expression of TAPP2 reduced ESCC cell TE1 migration by wound-healing assays and transwell migration assays, and it was concurrent with the decreased expression of the phosphorylation of AKT. Taken together, these findings suggested that TAPP2 serves as oncogenic gene in ESCC and may serve as a new target for ESCC therapy.

Plasma-Facilitated Synthesis of Amidoxime/Carbon Nanofiber Hybrids for Effective Enrichment of 238U(VI) and 241Am(III).

Plasma- and chemical-grafted amidoxime/carbon nanofiber hybrids (p-AO/CNFs and c-AO/CNFs) were utilized to remove 238U(VI) and 241Am(III) from aqueous solutions, seawater, and groundwater. Characteristic results indicated more nitrogen-containing groups in p-AO/CNFs compared to c-AO/CNFs. The maximum adsorption capacities of p-AO/CNFs at pH 3.5 and T = 293 K (588.24 mg of 238U(VI)/g and 40.79 mg of 241Am(III)/g from aqueous solutions, respectively) were significantly higher than those of c-AO/CNFs (263.18 and 22.77 mg/g for 238U(VI) and 241Am(III), respectively), which indicated that plasma-grafting was a highly effective, low-cost, and environmentally friendly method. Adsorption of 238U(VI) on AO/CNFs from aqueous solutions was significantly higher than that of 238U(VI) from seawater and groundwater; moreover, AO/CNFs displayed the highest effective selectivity for 238U(VI) compared to the other radionuclides. Adsorption of 238U(VI) onto AO/CNFs created inner-sphere complexes (e.g., U-C shells) as shown by X-ray absorption fine structure analysis, which was supported by surface complexation modeling. Three inner-sphere complexes gave excellent fits to pH-edge and isothermal adsorption of 238U(VI) on the AO/CNFs. These observations are crucial for the utilization of plasma-grafted, AO-based composites in the preconcentration and immobilization of lanthanides and actinides in environmental remediation.

Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer.

Celastrus orbiculatus is a traditional medicinal plant used in the anti-inflammatory and analgesic treatment of various diseases. A previous study demonstrated that ethyl acetate extract of C. orbiculatus (COE) exhibited significant antitumor effects. However, studies concerning the effects and mechanism of COE in terms of suppressing the epithelial-mesenchymal transition (EMT) in human gastric adenocarcinoma cells have not been performed at present. The present study hypothesized that COE may inhibit EMT in gastric adenocarcinoma cells by regulating cell cytoskeleton rearrangement. The effect of COE on the viability of AGS cells was detected by MTT assay. An EMT model was induced by transforming growth factor-ß1. Cell cytoskeleton staining, laser scanning confocal microscopy and electronic microscopy were used to detect the changes in cell morphology and microstructure of gastric adenocarcinoma cells prior and subsequent to COE treatment. Invasion and migration assays were used to observe the effect of COE on the metastatic ability of AGS cells in vitro. The effect of COE on the expression of Cofilin 1 and EMT biomarkers, including Epithelial-cadherin, Neural-cadherin, Vimentin and matrix metalloproteinases, was examined by western blotting in AGS cells. The correlation between Cofilin 1 and EMT was investigated with immunofluorescence and cytoskeleton staining methods. The results demonstrated that COE may significantly inhibit the process of EMT in AGS cells, and that this was concentration-dependent. In addition, COE significantly downregulated the level of Cofilin 1 in a concentration-dependent manner. In conclusion, these results suggested that Cofilin 1 was directly involved in the process of EMT in AGS cells, and that it served an important function. COE may significantly inhibit EMT in AGS cells, potentially by inhibiting the activation of the Cofilin 1 signaling pathway. The present study may provide a basis for the development of novel anticancer drugs and the development of novel therapeutic strategies, targeting Cofilin 1 protein.

Celastrus orbiculatus extract inhibits the migration and invasion of human glioblastoma cells in vitro.

BACKGROUND: Gliomas are highly aggressive tumors of the nervous system, and current treatments fail to improve patient survival. To identify substances that can be used as treatments for gliomas, we examined the effect of Celastrus orbiculatus extract (COE) on the invasion and migration of human glioblastoma U87 and U251 cells in vitro. METHODS: The effects of COE on cell viability and adhesion were tested using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cell adhesion assay, respectively. The effects of COE on cell migration and invasion were assessed by a wound-healing assay and transwell migration and invasion assays. The effects of COE on the expression of epithelial-mesenchymal transition (EMT)-related proteins and matrix metalloproteinases (MMPs) were evaluated using western blot and gelatin zymography, respectively. Finally, the effect of COE on actin assembly was observed using phalloidin-tetramethylrhodamine isothiocyanate labeling and confocal laser scanning microscopy. RESULTS: We found that COE inhibited the adhesion, migration, and invasion of U87 and U251 cells in a dose-dependent manner. COE reduced N-cadherin and vimentin expression, increased E-cadherin expression, and reduced MMP-2 and MMP-9 expression in U87 and U251 cells. Furthermore, COE inhibited actin assembly in U87 and U251 cells. CONCLUSIONS: COE attenuates EMT, MMP expression, and actin assembly in human glioblastoma cells, thereby inhibiting their adhesion, migration, and invasion in vitro.