Applications of Functionalized Fullerenes in Tumor Theranostics

Functionalized fullerenes with specific physicochemical properties have been developed for cancer diagnosis and therapy. Notably, metallofullerene is a new class of magnetic resonance imaging (MRI) contrast-enhancing agent, and may have promising applications for clinical diagnosis. Polyhydroxylated and carboxyl fullerenes have been applied to photoacoustic imaging. Moreover, in recent years, functionalized fullerenes have shown potential in tumor therapies, such as photodynamic therapy, photothermal treatment, radiotherapy and chemotherapeutics. Their antitumor effects may be associated with the modulation of oxidative stress, anti-angiogenesis, and immunostimulatory activity. While various types of novel nanoparticle agents have been exploited in tumor theranostics, their distribution, metabolism and toxicity in organisms have also been a source of concern among researchers. The present review summarizes the potential of fullerenes as tumor theranostics agents and their possible underlying mechanisms are discussed

Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma

Objective. To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). Methods. First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package “MethylMix”. Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylationspecific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. Results. Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. Conclusion. These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration

Mapping Spatial Variations of Structure and Function Parameters for Forest Condition Assessment of the Changbai Mountain National Nature Reserve

Forest condition is the baseline information for ecological evaluation and management. The National Forest Inventory of China contains structural parameters, such as canopy closure, stand density and forest age, and functional parameters, such as stand volume and soil fertility. Conventionally forest conditions are assessed through parameters collected from field observations, which could be costly and spatially limited. It is crucial to develop modeling approaches in mapping forest assessment parameters from satellite remote sensing. This study mapped structure and function parameters for forest condition assessment in the Changbai Mountain National Nature Reserve (CMNNR). The mapping algorithms, including statistical regression, random forests, and random forest kriging, were employed with predictors from Advanced Land Observing Satellite (ALOS)-2, Sentinel-1, Sentinel-2 satellite sensors, digital surface model of ALOS, and 1803 field sampled forest plots. Combined predicted parameters and weights from principal component analysis, forest conditions were assessed. The models explained spatial dynamics and characteristics of forest parameters based on an independent validation with all r values above 0.75. The root mean square error (RMSE) values of canopy closure, stand density, stand volume, forest age and soil fertility were 4.6%, 33.8%, 29.4%, 20.5%, and 14.3%, respectively. The mean assessment score suggested that forest conditions in the CMNNR are mainly resulted from spatial variations of function parameters such as stand volume and soil fertility. This study provides a methodology on forest condition assessment at regional scales, as well as the up-to-date information for the forest ecosystem in the CMNNR

Interference of steroidogenesis by gold nanorod core/silver shell nanostructures: Implications for reproductive toxicity of silver nanomaterials

Silver nanomaterials are widely used in personal care products. Recent studies have indicated that these nanomaterials may penetrate the blood-placental barrier and gain access to the ovaries. It is largely unknown how silver nanomaterials influence ovarian physiology and functions such as hormone production. This study examines the in vitro toxicology of silver nanomaterials, focusing especially on cytotoxicity and steroidogenesis while exploring their underlying mechanisms. In this study, primary rat granulosa cells were exposed to gold nanorod core/silver shell nanostructures (Au@Ag NRs), which were compared to cells exposed to gold nanorods only. The Au@Ag NRs generated more reactive oxygen species (ROS), reduced mitochondrial membrane potential, and decreased production of adenosine triphosphate. Au@Ag NRs promoted steroidogenesis, including progesterone and estradiol, in a time and dose-dependent manner. Chemical reactivity and transformation of Au@Ag NRs were then studied by electron spin resonance spectroscopy (ESR) and X-ray absorption near edge structure, which identified the generation of free radicals and intracellular silver species. These results suggested that both particle-specific activity and intracellular silver ion release of Au@Ag Please click Additional Files below to see the full abstract

Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device

Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell’s membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (\u3c2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz–2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field. Further experiments specifically targeting the two types of cancer cells using HER2 antibody functionalized gold nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field strength can be induced via the application of nanoparticles, consequently leading to the killing of the cancerous cells without affecting non cancerous HUVECs and MCF10a providing a platform for the development of a non-invasive cancer treatment without any harmful side effects. The EIS was used to monitor the real-time consequences on cellular viability and a noticeable decrease in the growth profile of the MCF7 was observed with the application of the HER2-AuNPs and the electric fields indicating specific inhibitory effects on dividing cells in culture. To further understand the effects of the externally applied field to the cells, an Annexin V/EthD-III assay was performed to determine the cell death mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7 before and after incorporation of the HER2-AuNPs was also obtained indicating a decrease in zeta potential with the incorporation of the nanoparticles. The outcome of this research will improve our fundamental understanding of the behavior of cancer cells and define optimal parameters of electrotherapy for clinical and drug delivery applications

Single Nucleotide Polymorphisms in Selected Apoptotic Genes and BPDE-Induced Apoptotic Capacity in Apparently Normal Primary Lymphocytes: A Genotype-Phenotype Correlation Analysis

Apoptotic capacity (AC) in primary lymphocytes may be a marker for cancer susceptibility, and functional single nucleotide polymorphisms (SNPs) in genes involved in apoptotic pathways may modulate cellular AC in response to DNA damage. To further examine the correlation between apoptotic genotypes and phenotype, we genotyped 14 published SNPs in 11 apoptosis-related genes (i.e., p53, Bcl-2, BAX, CASP9, DR4, Fas, FasL, CASP8, CASP10, CASP3, and CASP7) and assessed the AC in response to benzo[a]pyrene-7,8-9,10-diol epoxide (BPDE) in cultured primary lymphocytes from 172 cancer-free subjects. We found that among these 14 SNPs, R72P, intron 3 16-bp del/ins, and intron 6 G>A in p53, −938C>A in Bcl-2, and I522L in CASP10 were significant predictors of the BPDE-induced lymphocytic AC in single-locus analysis. In the combined analysis of the three p53 variants, we found that the individuals with the diplotypes carrying 0-1 copy of the common p53 R-del-G haplotype had higher AC values compared to other genotypes. Although the study size may not have the statistical power to detect the role of other SNPs in AC, our findings suggest that some SNPs in genes involved in the intrinsic apoptotic pathway may modulate lymphocytic AC in response to BPDE exposure in the general population. Larger studies are needed to validate these findings for further studying individual susceptibility to cancer and other apoptosis-related diseases

Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation.

Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage