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

Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways

BACKGROUND: RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 has been demonstrated to be a tumor suppressor. Current researches in vitro confirm that RBM5 can suppress the growth of lung adenocarcinoma cells by inducing apoptosis. There is still no effective model in vivo, however, that thoroughly investigates the effect and molecular mechanism of RBM5 on lung adenocarcinoma. METHOD: We established the transplanted tumor model on BALB/c nude mice using the A549 cell line. The mice were treated with the recombinant plasmids carried by attenuated Salmonella to induce the overexpression of RBM5 in tumor tissues. RBM5 overexpression was confirmed by immunohistochemistry staining. H&E staining was performed to observe the histological performance on plasmids-treated A549 xenografts. Apoptosis was assessed by TUNEL staining with a TUNEL detection kit. Apoptosis-regulated genes were detected by Western blot. RESULTS: We successful established the lung adenocarcinoma animal model in vivo. The growth of tumor xenografts was significantly retarded on the mice treated with pcDNA3.1-RBM5 carried by attenuated Salmonella compared to that on mice treated with pcDNA3.1. Overexpression of RBM5 enhanced the apoptosis in tumor xenografts. Furthermore, the expression of Bcl-2 protein was decreased significantly, while the expression of BAX, TNF-α, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and cleaved PARP proteins was significantly increased in the pcDNA3.1-RBM5-treated mice as compared to that in the control mice. CONCLUSIONS: In this study, we established a novel animal model to determine RBM5 function in vivo, and concluded that RBM5 inhibited tumor growth in mice by inducing apoptosis. The study suggests that although RBM5’s involvement in the death receptor-mediated apoptotic pathway is still to be investigated, RBM5-mediated growth suppression, at least in part, employs regulation of the mitochondrial apoptotic pathways

Fatty Acid Analysis of the Transgenic Tobacco Expressing A Delta 6-Desaturase Gene from \u3cem\u3eMicroula sikkimensis\u3c/em\u3e

γ-Linolenic acid (GLA, 18:3Δ6, 9, 12) and octadecatetraenoic acid (OTA, 18:4Δ6, 9, 12, 15) are important polyunsaturated fatty acids (PUFAs), which have been proved to be benefit for human health (Fan and Chapkin 1998; Whelan 2009). Currently, fish are the predominant source of PUFAs. However, with the growth of world’s population and the more nutrition requirements, fishery resources are shrinking. Alternative sources of PUFAs are being investigated (Truksa et al. 2009). The major oil crops do not contain GLA and OTA, only several plant species contain these important fatty acids in their leaf lipids and seed oils (Zhou et al. 2006). Genetic modification of oil crops may be an effective approach to produce these fatty acids. This process requires an enzyme–delta 6-desaturase, which can introduce a double bond at the delta 6 position (Meesa-pyodsuk and Qiu 2012). Microula sikkimensis is a kind of rare wild oil plant, which is widely distributed in Bhutan, Sikkim, Nepal and the northwest region of China (Cao and Suo 2010). Fu et al. (1997) reported that unsaturated fatty acids made up 86.5% of total fatty acids, and that GLA accounted for 6.4% of fatty acids in M. sikkimensis seeds that is known as a new source of GLA. In this research, the delta 6-desaturase gene of M. sikkimensis was introduced into tobacco and the fatty acid composition of transgenic tobacco was analysed

Influence of chemical oxidant on degradation of benzo[a]pyrene metabolites by the bacterium-Zoogloea sp.

It is neither comprehensive nor appropriate that the bioremediation of a benzo[a]pyrene (BaP)-contaminated environment be assessed only by its high degradation extent because its metabolites\u27 chemical structures are similar to the parent compound and maybe equally toxic. Therefore, further degradation of BaP metabolites is significant. Three methods, combining the Zoogloea sp. with potassium permanganate, combining the Zoogloea sp. with H2O2, Zoogloea sp. alone, were investigated to degrade cis-BP4,5-dihydrodiol and cis-BP7,8-dihydrodiol, which are the metabolites of BaP formed by bacterium-Zoogloea sp. Optimum parameters of degradation in the best method are that: of the three methods, coupling the Zoogloea sp. and KMnO4 is the best; compared with cis-BP7,8-dihydrodiol, cis-BP4,5-dihydrodiol is the more liable to be accumulated in pure cultures; the degradation effect of the two metabolites is optimal when the initial concentration of KMnO4 in the cultures is 0.05%; initial concentration of cis-BP4,5-dihydrodiol and cis-BP7,8-dihydrodiol is 4 mg L&minus;1, 8 mg L&minus;1, respectively; cometabolic substance is salicylic acid or sodium succinate. The degradation extent of cis-BP4,5-dihydrodiol and cis-BP7,8-dihydrodiol using combining the Zoogloea sp. and KMnO4 reach 76.1% and 85.9% after 12 days of cultivation, respectively, which were more than twice compared with conventional method.<br /

Screening Key Indicators for Acute Kidney Injury Prediction Using Machine Learning

Acute kidney injury is a common critical disease with a high mortality. The large number of indicators in AKI patients makes it difficult for clinicians to quickly and accurately determine the patient’s condition. This study used machine learning methods to filter key indicators and use key indicator data to achieve advance prediction of AKI so that a small number of indicators could be measured to reliably predict AKI and provide auxiliary decision support for clinical staff. Sequential forward selection based on feature importance calculated by XGBoost was used to screen out 17 key indicators. Three machine learning algorithms were used to make predictions, namely, logistic regression (LR), decision tree, and XGBoost. To verify the validity of the method, data were extracted from the MIMIC III database and the eICU-CRD database for 1,009 and 1,327 AKI patients, respectively. The MIMIC III database was used for internal validation, and the eICU-CRD database was used for external validation. For all three machine learning algorithms, the prediction performance from using only the key indicator dataset was very close to that from using the full dataset. The XGBoost algorithm performed the best, and LR was the next best. The decision tree performed the worst. The key indicator screening method proposed in this study can achieve a good predictive performance while streamlining the number of indicators

Effect of tumor and normal lung volumes on the lung volume–dose parameters of IMRT in non–small-cell lung cancer

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p&lt;0.001,&nbsp;p=0.004,&nbsp;p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p&lt;0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3)