Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common type of cancer, with a mortality of >80% worldwide. Gigantol is a bibenzyl compound that displays anticancer activity. The aim of the present study was to determine the biological activity of gigantol in NSCLC and to elucidate the underlying molecular mechanism of its action. The expression of DEK proto-oncogene (DEK) was measured in NSCLC tissues and cell lines by reverse transcription-quantitative PCR (RT-qPCR). The results suggested that DEK levels were significantly increased in NSCLC tissues and cell lines compared with adjacent non-tumor tissues and BEAS-2B normal bronchial epithelial cells, respectively. A549 cells were exposed to a series of gigantol concentrations (0, 25, 50 and 100 µM) and transfected with DEK small interfering RNA. The results of cell viability measured by MTT assay indicated that gigantol significantly decreased cell viability. Additionally, cell proliferation was assessed by CCK-8 and apoptosis was measured by flow cytometry. In comparison with the control group, gigantol treatment inhibited cell proliferation and promoted apoptosis, whereas DEK knockdown increased gigantol-induced suppression of proliferation and acceleration of apoptosis. Additionally, DEK overexpression reversed gigantol-induced effects on proliferation and apoptosis. Moreover, compared with the control group, gigantol treatment decreased Ki-67 and Bcl-2 expression levels, increased Bax expression levels and inactivated the Wnt/ß-catenin signaling pathway, as assessed by RT-qPCR and/or western blot. DEK knockdown further increased gigantol-induced effects, but DEK overexpression reversed gigantol-induced effects. To conclude, the results of the present study suggested that gigantol inhibited cell proliferation and induced apoptosis by decreasing Ki-67 and Bcl-2 expression, increasing Bax expression and activating the Wnt/ß-catenin signaling pathway by regulating DEK. The present study indicated the therapeutic potential of gigantol in patients with NSCLC. In addition, DEK may serve as a novel therapeutic target to enhance the effects of gigantol treatment.

Expression levels of blood platelet and C-reactive protein in patients with severely pneumonic and their predictive values for efficacy.

This paper aims to detect the expression levels of blood platelet (PLT) and C-reactive protein (CRP) in severely pneumonic patients and analyze their correlation. For this purpose, eighty-one severely pneumonic patients were retrospectively selected as an observation group and 106 healthy people as a control group. Pretreatment and post-treatment expression levels of PLT and CRP, their predictive values for efficacy, and correlation of PLT, CRP, and PSI scores in observation group after treatment were analyzed. Before treatment, the expression level of PLT in the observation group was higher than the control group (P< 0.05). In the observation group, the expression level of PLT after treatment was significantly lower than that before treatment (P< 0.05). Before treatment, the expression level of CRP in the observation group was higher than the control group (P< 0.05). In the observation group 1) the pretreatment PLT expression level was higher than that in the control group; 2) the post-treatment PLT expression level was significantly lower than that in the pretreatment one; 3) the pretreatment CRP expression level was higher than that in the control group; and 4) the post-treatment CRP expression level was significantly lower than the pretreatment one (All P-values< 0.05). Based upon the efficacy, the observation group was divided into an effective group and an invalid group. The post-treatment expression levels of PLT and CRP in the effective group were lower than those in the invalid group (P< 0.05). Based upon the ROC curve, the area under curves (AUC) of PLT, CRP, and joint detection were 0.843, 0.864, and 0.886, respectively. When the cut-off point was > 0.579, the best specificity and sensitivity were 98.44 and 70.59%, respectively. According to the Pearson test, positive correlations existed between PLT and CRP, between PLT and PSI scores, and between CRP and PSI scores. In conclusion, the expression levels of PLT and CRP in severely pneumonic patients might be used to evaluate the efficacy and conducive to detection of the disease, which have high application values in clinic.

PGC-1α activator-induced fatty acid oxidation in tumor-infiltrating CTLs enhances effects of PD-1 blockade therapy in lung cancer.

PURPOSE: The present study aims to investigate the efficacy and mechanisms of peroxisome proliferator-activated receptor γ coactivator 1-α agonist, as adjuvant to programmed death-1 (PD-1) blockade in hyporesponsive lung cancer cells-derived in vivo tumor model, using bezafibrate. METHODS: Mouse Lewis lung carcinoma (LLC) xenograft models were established and treated with programmed death-ligand 1 (PD-L1) monoclonal antibodies with or without bezafibrate. Tumors or peripheral blood of mice were harvested to investigate the quality, quantity, and function as well as energetic metabolism of cytotoxic T lymphocytes (CTLs) by flow cytometry or quantitative real-time polymerase chain reaction. RESULTS: The combination of bezafibrate plus anti-PD-L1 reached synergistic tumoricidal effect in LLC xenograft mouse models, even though bezafibrate alone had no effect on tumor growth. Bezafibrate significantly facilitated CD8+ T cells infiltrating into tumor tissues by enhancing the expression of CXCL9 and CXCL10 within tumors as well as the receptor CXCR3 in infiltrating CTLs. Activated CTLs within tumors were also significantly upregulated by bezafibrate. Further data demonstrated that bezafibrate treatment could maintain the survival and functional capacity of tumor-infiltrating CTLs. Moreover, cellular reactive oxygen species in infiltrating CTLs and fatty acid oxidation (FAO)-related genes (PGC-1α, Cpt1a, and LCAD) expression within tumors were significantly increased after treatment with bezafibrate. CONCLUSIONS: Bezafibrate synergized the tumoricidal effect of PD-1 blockade in hyporesponsive lung cancer by expansion of effector CTLs within tumor microenvironment. The potential mechanism may relate to the capacity of bezafibrate in regulating FAO of tumor-infiltrating CTLs.

A compact repetitive high-voltage nanosecond pulse generator for the application of gas discharge.

Uniform and stable discharge plasma requires very short duration pulses with fast rise times. A repetitive high-voltage nanosecond pulse generator for the application of gas discharge is presented in this paper. It is constructed with all solid-state components. Two-stage magnetic compression is used to generate a short duration pulse. Unlike in some reported studies, common commercial fast recovery diodes instead of a semiconductor opening switch (SOS) are used in our experiment that plays the role of SOS. The SOS-like effects of four different kinds of diodes are studied experimentally to optimize the output performance. It is found that the output pulse voltage is higher with a shorter reverse recovery time, and the rise time of pulse becomes faster when the falling time of reverse recovery current is shorter. The SOS-like effect of the diodes can be adjusted by changing the external circuit parameters. Through optimization the pulse generator can provide a pulsed voltage of 40 kV with a 40 ns duration, 10 ns rise time, and pulse repetition frequency of up to 5 kHz. Diffuse plasma can be formed in air at standard atmospheric pressure using the developed pulse generator. With a light weight and small packaging the pulse generator is suitable for gas discharge application.

Citrinin selective molecularly imprinted polymers for SPE.

Molecularly imprinted polymers (MIPs) for citrinin (Cit) with 1-hydroxy-2-naphthoic acid (HNA) as mimic template were prepared and the molecularly imprinted SPE method was developed for the detection of Cit in rice with HPLC. The adsorption properties of HNA and Cit on the MIPs and nonimprinted polymers were investigated. It proved that MIPs showed higher selectivity adsorption to HNA and Cit than nonimprinted polymers were. The recoveries of Cit in rice were in the range of 86.7-97.7%. The spiked rice samples and five rice samples in Beijing market were detected using molecularly imprinted SPE method and satisfied results were obtained as discussed in this article.

Expression of signal transducers and activator of transcription 3 (STAT3) determines differentiation of olfactory bulb cells.

Signal transducers and activator of transcription (STAT) proteins are activated in response to many cytokines and growth factors. Many studies indicated that regulation of STAT expression plays an important role in survival, growth, and differentiation of neurons and glias in response to ciliary neurotropic factor, including rehabilitation of rat cortical injury, nerve regeneration, gangliosides-mediated stimulation of rat and murine primary microglia, and differentiation of retinal neurons. In this study, we use olfactory bulb neurons as a useful model, which undergo strong neurogenesis throughout adulthood. Our research demonstrated that low level of STAT3 expression facilitates the terminal differentiation of olfactory bulb neurons as well as induces the generation of neurons from neural stem cells, which can be potentially used in future therapies. On the contrary, activation of STAT3 expression is essential to the maintenance of stem-like status in olfactory cells. This activation can be manipulated by leukemia inhibitory factor (LIF), a member of cytosolic tyrosine kinases. All these results implicate that STAT3 serves as a critical protein in regulating the differentiation state in neural cells.

Nanosize titanium dioxide cause neuronal apoptosis: a potential linkage between nanoparticle exposure and neural disorder.

OBJECTIVES: Nanosize titanium dioxide is used in water and air decontamination and in numerous home appliances and products designed for direct human use. However, the impact of nanoparticle on biological system is not known to us. Therefore, it is our urgent and primary task to ascertain the information about safety and potential hazards of products derived from nanomaterial to the health of mankind. METHODS: We made use of MTT, bromodeoxyuridine (BrdU), and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays to testify the biological impact of nanosize TiO2 on olfactory bulb neurons cultured in vitro. RESULTS: In this article, we elucidate the cytotoxicity of titanium dioxide to olfactory bulb neurons on cellular and molecular level. We come to a conclusion that nanosize titanium dioxide causes neuronal apoptosis, and it also down-regulate the expression of olfactory marker protein (OMP) and tyrosine hydroxylase (TH). DISCUSSION: These results show that a relationship between nanoparticle exposure and pathogeny of neurodegenerative diseases may exist.