[Retracted] Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN­55,212­2.

[This retracts the article DOI: 10.3892/ol.2015.3525.].

Diagnostic efficiency of multi-modal MRI based deep learning with Sobel operator in differentiating benign and malignant breast mass lesions-a retrospective study.

Purpose: To compare the diagnostic efficiencies of deep learning single-modal and multi-modal for the classification of benign and malignant breast mass lesions. Methods: We retrospectively collected data from 203 patients (207 lesions, 101 benign and 106 malignant) with breast tumors who underwent breast magnetic resonance imaging (MRI) before surgery or biopsy between January 2014 and October 2020. Mass segmentation was performed based on the three dimensions-region of interest (3D-ROI) minimum bounding cube at the edge of the lesion. We established single-modal models based on a convolutional neural network (CNN) including T2WI and non-fs T1WI, the dynamic contrast-enhanced (DCE-MRI) first phase was pre-contrast T1WI (d1), and Phases 2, 4, and 6 were post-contrast T1WI (d2, d4, d6); and Multi-modal fusion models with a Sobel operator (four_mods:T2WI, non-fs-T1WI, d1, d2). Training set (n = 145), validation set (n = 22), and test set (n = 40). Five-fold cross validation was performed. Accuracy, sensitivity, specificity, negative predictive value, positive predictive value, and area under the ROC curve (AUC) were used as evaluation indicators. Delong's test compared the diagnostic performance of the multi-modal and single-modal models. Results: All models showed good performance, and the AUC values were all greater than 0.750. Among the single-modal models, T2WI, non-fs-T1WI, d1, and d2 had specificities of 77.1%, 77.2%, 80.2%, and 78.2%, respectively. d2 had the highest accuracy of 78.5% and showed the best diagnostic performance with an AUC of 0.827. The multi-modal model with the Sobel operator performed better than single-modal models, with an AUC of 0.887, sensitivity of 79.8%, specificity of 86.1%, and positive prediction value of 85.6%. Delong's test showed that the diagnostic performance of the multi-modal fusion models was higher than that of the six single-modal models (T2WI, non-fs-T1WI, d1, d2, d4, d6); the difference was statistically significant (p = 0.043, 0.017, 0.006, 0.017, 0.020, 0.004, all were greater than 0.05). Conclusions: Multi-modal fusion deep learning models with a Sobel operator had excellent diagnostic value in the classification of breast masses, and further increase the efficiency of diagnosis.

Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages.

Multi-organ failure caused by the inflammatory cytokine storm induced by severe infection is the major cause of death for sepsis. Sj-Cys is a cysteine protease inhibitor secreted by Schistosoma japonicum with strong immunomodulatory functions on host immune system. Our previous studies have shown that treatment with Sj-Cys recombinant protein (rSj-Cys) attenuated inflammation caused by sepsis. However, the immunological mechanism underlying the immunomodulation of Sj-Cys for regulating inflammatory diseases is not yet known. In this study, we investigated the effect of Sj-Cys on the macrophage M2 polarization and subsequent therapeutic effect on sepsis. The rSj-Cys was expressed in yeast Pichia pastoris. Incubation of mouse bone marrow-derived macrophages (BMDMs) with yeast-expressed rSj-Cys significantly activated the polarization of macrophages to M2 subtype characterized by the expression of F4/80+ CD206+ with the elated secretion of IL-10 and TGF-ß. Adoptive transfer of rSj-Cys treated BMDMs to mice with sepsis induced by cecal ligation and puncture (CLP) significantly improved their survival rates and the systemic clinical manifestations of sepsis compared with mice receiving non-treated normal BMDMs. The therapeutic effect of Sj-Cys-induced M2 macrophages on sepsis was also reflected by the reduced pathological damages in organs of heart, lung, liver and kidney and reduced serological levels of tissue damage-related ALT, AST, BUN and Cr, associated with downregulated pro-inflammatory cytokines (IFN-gamma and IL-6) and upregulated regulatory anti-inflammatory cytokines (IL-10 and TGF-ß). Our results demonstrated that Sj-Cys is a strong immunomodulatory protein with anti-inflammatory features through activating M2 macrophage polarization. The findings of this study suggested that Sj-Cys itself or Sj-Cys-induced M2 macrophages could be used as therapeutic agents in the treatment of sepsis or other inflammatory diseases.

Fabrication and Characteristics of Reduced Graphene Oxide Produced with Different Green Reductants.

There has been an upsurge of green reductants for the preparation of graphene materials taking consideration of human health and the environment in recent years. In this paper, reduced graphene oxides (RGOs) were prepared by chemical reduction of graphene oxide (GO) with three green reductants, L-ascorbic acid (L-AA), D-glucose (D-GLC) and tea polyphenol (TP), and comparatively characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectra, Raman spectra and electrical conductivity analysis. Results showed that all these three reductants were effective to remove oxygen-containing functional groups in GO and restore the electrical conductivity of the obtained RGO. The RGO sample with L-ascorbic acid as a reductant and reduced with the existence of ammonia had the highest electrical conductivity (9.8 S·cm(-1)) among all the obtained RGO samples. The mechanisms regarding to the reduction of GO and the dispersion of RGO in water were also proposed. It is the good dispersibility of reduced graphene oxide in water that will facilitate its further use in composite materials and conductive ink.

Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2.

Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. The present study aimed to identify novel therapeutic strategies for osteosarcoma, by assessing the antitumor activity of the cannabinoid WIN-55,212-2 and its combined effect with adriamycin (ADM) against the MG-63 human osteosarcoma cell line. To evaluate the antiproliferative action of these molecules, a Cell Counting kit-8 (CCK-8) assay was used. The ability of cannabinoid to inhibit the migration, invasion and angiogenic activity of MG-63 cells were assessed by scratch, Transwell® chamber and angiogenesis assays, respectively, in vitro. To examine the alterations in expression of targeted genes, quantitative polymerase chain reaction and western blot analysis were used. The administration of cannabinoid combined with ADM was demonstrated to inhibit the growth of MG-63 cells, resulting in a cell viability of 32.12±3.13%, which was significantly lower (P<0.05) compared with the cell viability following treatment with cannabinoid (70.86±7.55%) and ADM (62.87±5.98%) alone. Greater antimetastasis and antiangiogenic activities were also observed following the coadministration of the two agents compared with individual treatments and controls. In addition, the expression levels of Notch-1, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in MG-63 cells were downregulated following the treatments with cannabinoid alone or in combination with ADM. In conclusion, the present findings demonstrated that cannabinoid WIN-55,212-2 may significantly potentiate the antiproliferative, antimetastasis and antiangiogenic effects of ADM against MG-63 cells via the downregulation of Notch-1, MMP-2 and VEGF. These findings may offer a novel strategy for the treatment of osteosarcoma.

MicroRNA-17-5p induces drug resistance and invasion of ovarian carcinoma cells by targeting PTEN signaling.

BACKGROUND: The miR-17-5p was overexpressed in ovarian cancer cells, and those cells were treated with paclitaxel. The proliferation of ovarian cancer cells was assessed by MTT assay. The Caspase-Glo3/7 and TUNEL assay were used to examine the effect of miR-17-5p on paclitaxel-induced apoptosis in ovarian cancer cells. The migration and invasion of ovarian cancer cells were analyzed by BD matrigel assays. Western blot was performed to evaluate the expression of apoptotic proteins and epithelial-mesenchymal transition markers in ovarian cancer cells. RESULTS: The survival rate of ovarian cancer cells was increased after overexpression of miR-17-5p. The apoptosis decreased in miR-17-5p overexpressed ovarian cancer cells. Altered miR-17-5p expression affected migration and invasion of ovarian cancer cells. The overexpression of miR-17-5p altered the expression of EMT markers. miR-17-5p activates AKT by downregulation of PTEN in ovarian cancer cells. CONCLUSION: Our results indicate that miR-17-5p might serve as potential molecular therapeutic target.

Microarray and ChIP-seq data analysis revealed changes in p53-mediated transcriptional regulation in Nutlin-3-treated U2OS cells.

Integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) data and microarray data was performed to illustrate the effect of Nutlin­3 on promoter selectivity and transcriptional regulation by the tumor suppressor p53 in U2OS human osteosarcoma cells. Raw data (accession number, GSE46642) were downloaded from Gene Expression Omnibus. Differential analyses were performed using package limma of R software. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integration Discovery. Integrative analysis of ChIP­seq data and microarray data were confirmed with ChIP­Array. A total of 565 DEGs were identified, including 373 upregulated genes and 192 downregulated genes. Genes involved in the p53 signaling pathway, cell cycle, DNA replication, cytokine­cytokine receptor interaction and melanoma were markedly over­represented in the DEGs. A total of 39 DEGs were directly regulated by p53 and two were the transcription factors (TFs), E2F2 and HOXA1. E2F2 regulated 25 DEGs, while HOXA1 regulated one DEG. The cell cycle, p53 signaling pathway, melanoma and pathways involved in cancer were enriched in the direct and indirect target genes. Changes in the p53­binding pattern induced by Nutlin­3 were described in the present study, which may advance the understanding of the regulatory network of p53 in osteosarcoma and aid in the development of novel therapies.

Identification and functional analysis of differentially expressed genes related to metastatic osteosarcoma.

BACKGROUND: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. MATERIALS AND METHODS: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). RESULTS: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. CONCLUSIONS: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS.