Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma.

This study aimed to compare the gene expression variation of clinical primary osteosarcoma (OS) and metastatic OS, identify expression profiles and signal pathways related to disease classification, and systematically evaluate the potential anticancer effect and molecular mechanism of ginsenoside Rh2 on OS. A raw dataset (GSE14359), which excluded GSM359137 and GSM359138, was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and principal component analysis (PCA) were obtained with limma. Pathways enrichment analysis was understood by GSEA app. Rh2-associated targets were harvested and mapped through PharmMapper and Cytoscape 3.4.0. The toxicity of Rh2 was determined using crystal staining and MTT assay on 143B and MG63 cell lines. The relative protein expression was confirmed through Western blot analysis. The mitochondrial membrane potential (△Ψm) was evaluated by JC-1 fluorescence staining. The cell mobility was measured via wound healing and transwell assays. A total of 752 genes were upregulated, while 161 genes were downregulated. GSEA and PCA displayed significant function enrichment and classification. Through PharmMapper and Cytoscape 3.4.0, Rh2 was found to target the mitogen activated protein kinase (MAPK) and PI3K signaling pathways, which are the key pathways in the metastasis of OS. Furthermore, Rh2 induced a concentration-dependent decrease in cell viability and early apoptosis associated with ΔΨm decline, while a non-lethal dose of Rh2 weakened the metastatic capability. Moreover, systematic evaluation showed that promoting the MAPK signaling pathway and inhibiting PI3K/Akt/mTOR were correlated with the anticancer effects of Rh2 on metastatic OS. In conclusion, transcriptome-derived approaches may be beneficial in diagnosing early metastases, and Rh2, a multi-targeting agent, shows promising application potential in suppressing metastatic OS in an MAPK- and PI3K/Akt/mTOR-dependent manner.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Integration of Fe3O4 with Bi2S3 for Multi-Modality Tumor Theranostics.

The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) holds a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe3O4@polydopamine (PDA)@bovine serum albumin (BSA)-Bi2S3 composite as a theranostic agent, by chemically linking the Fe3O4@PDA with BSA-Bi2S3 via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe3O4 NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H2O2 in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA could prevent the oxidization of Fe3O4, thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi2S3 component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi2S3 endow the Fe3O4@PDA@BSA-Bi2S3 composite with an excellent photothermal transforming ability which could lead to tumor hyperthermia. All of these merits play the synergism with the tumor microenvironment and qualify the Fe3O4@PDA@BSA-Bi2S3 NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.

Correction: Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

Correction for 'Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy' by Yangjie Xu et al., Soft Matter, 2020, 16, 132-141.

Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

In this study, sodium alginate (ALG)/poly dopamine (PDA)-polyvinylpyrrolidone (PVP) nanocomposites was synthesized via a one-step electrostatic spraying method. The spinning solution of ALG and dopamine was electrostatically sprayed into an alkaline solution of PVP, calcium chloride and tris buffer (pH = 8.5), in which the gelation of ALG and the polymerization of dopamine could be simultaneously triggered. PDA hence produced possesses a high photothermal conversion efficiency, while the PVP that was facilely conjugated onto the surface of nanocomposites improves the colloidal stability and compatibility of the material. Moreover, the ALG renders the nanocomposite excellent drug (doxorubicine, DOX) loading capacity. Promisingly, the temperature increment during the PTT process could promote the DOX release, thus enhancing its therapeutic effect. The in vitro/in vivo biosafety and tumor treatment experiments further corroborate that the ALG/PDA-PVP nanocomposites have remarkable biocompatibility and synergism for tumor hyperthermia and chemotherapy. Consequently, such a one-step electrospray strategy provides a new way for designing nanomaterials and is expected to significantly promote the development of organic photothermal therapeutic agents with excellent bio-compatibility.

Synthesis of a Clay-Based Nanoagent for Photonanomedicine.

Photo-induced cancer therapies, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), have attracted numerous attentions owing to the high selectivity, convenience, and few side effects. However, single PTT usually requires high laser power density, and single PDT usually needs a high photosensitizer dosage. Herein, a kind of composite nanocarrier based on clay (laponite)-polypyrrole (LP) nanodisks was synthesized via the in situ polymerization of pyrrole in the interlayer space of laponite. LP composite nanodisks were then coated with polyvinylpyrrolidone (PVP) to form the LP-PVP (LPP) composite nanodisks which show an excellent colloidal stability and in vitro and in vivo biocompatibility. The interlayer space of LPP can be further used for the loading of Chlorin e6 (Ce6), with an ultrahigh loading capacity of about 89.2%. Furthermore, the LPP nanocarrier can enhance the PDT effect of Ce6 under the irradiation of a 660 nm laser, through enhancing its solubility and cellular uptake amount. Besides, it was found that LPP nanodisks exhibit a more outstanding photothermal performance under a 980 nm near-infrared laser (NIR) than a 808 nm NIR laser, with the photothermal conversion efficiency of 45.7 and 27.7%, respectively. The in vitro and in vivo tumor therapy results evidently confirm that the Ce6-loaded LPP nanodisks have a combined tumor PTT and PDT effect, which can significantly suppress the tumor malignant proliferation.

Roles of TNF-alpha gene polymorphisms in the occurrence and progress of SARS-Cov infection: a case-control study.

BACKGROUND: Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-alpha gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-alpha gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-alpha gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-alpha gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data. RESULTS: Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90-0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39-20.45) and 5.67(2.74-11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18-23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60-22.55) at -1031 site of TNF-alpha gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53-26.88) and the adjusted OR was 8.40(95%CI 1.76-40.02) in cured SARS patients compared to CC genotype. CONCLUSION: SNPs of TNF-alpha gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.