Self-Assemble Silk Fibroin Microcapsules for Cartilage Regeneration through Gene Delivery and Immune Regulation.

Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer-by-layer self-assembly, in which interleukin-4 (IL-4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self-assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL-4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk-based microcapsule delivery system can also provide strategies for the treatment of other diseases.

Improving the upper atmospheric temperature accuracy of the ground-based instrument by eliminating noise ways.

In view of the special properties of the upper atmosphere at the altitude of 80-120 km, a ground-based passive remote sensing instrument ground-based airglow volume emission rate and temperature imaging interferometer (GBAVTII) is built to detect the atmospheric temperature used O 2(0-1) spectral line of night airglow at the altitude of 94 km. In the process of photographing the upper atmosphere airglow with the GBAVTII, the stray light (white noise) such as moonlight, city lights, and starlight will be affected. In this paper, the theoretical expression of denoising is derived based on the rotational line temperature measurement of diatomic O 2(0-1) airglow. Through a slight adjustment of different parameters in the forward equation of the GBAVTII and noise reduction in laboratory flat-field fine calibration, and other denoising methods in the GBAVTII image processing process, the maximum accuracy of the GBAVTII detection of the upper atmospheric temperature is enhanced to 2.4 K. Also, the minimum error of the GBAVTII detecting data with the satellite instrument sounding of atmosphere using broadband emission radiometry is 0.4 K. Thus, the absolute accuracy of the GBAVTII in detecting the upper atmospheric temperature can be improved to ±(0.4-2.4)K through the theory and method studied in this paper.

Design, synthesis, and in vivo evaluation of GO-SWL-Ahx-K-SWL.

In order to acquire both expanded binding ability with the EphA2 receptor and superior drug delivery capacity, we designed and synthesized the modified GO-SWL-Ahx-K-SWL conjugate as a potential targeted therapeutic drug for non-small cell lung cancer (NSCLC). Various characterization methods have confirmed that the conjugate is consistent with the theoretical peptide. The cytotoxicity test results showed that the conjugate was slightly more toxic to A549 cells than in 3 T3 cells, and the toxicity increased in a concentration-dependent manner. Single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging was performed to evaluate the conjugate binding to EphA2 receptor in vivo. The images showed obvious radioactive concentration in tumor tissues and significantly higher ratios of the tumor and muscle in the 125I-GO-SWL-Ahx-K-SWL group (10.78) than in the 125I-SWL-Ahx-K-SWL group (5.21) at all three time points (P < 0.01).

Characteristics of Very Low Frequency Sound Propagation in Full Waveguides of Shallow Water.

This work is concerned with the characteristics of very low frequency sound propagation (VLF, ≤100 Hz) in the shallow marine environment. Under these conditions, the classical hypothesis of considering the sea bottom as a fluid environment is no longer appropriate, and the sound propagation characteristics at the sea bottom should be also considered. Hence, based on the finite element method (FEM), and setting the sea bottom as an elastic medium, a proposed model which unifies the sea water and sea bottom is established, and the propagation characteristics in full waveguides of shallow water can be synchronously discussed. Using this model, the effects of the sea bottom topography and the various geoacoustic parameters on VLF sound propagation and its corresponding mechanisms are investigated through numerical examples and acoustic theory. The simulation results demonstrate the adaptability of the proposed model to complex shallow water waveguides and the accuracy of the calculated acoustic field. For the sea bottom topography, the greater the inclination angle of an up-sloping sea bottom, the stronger the leak of acoustic energy to the sea bottom, and the more rapid the attenuation of the acoustic energy in sea water. The effect of a down-sloping sea bottom on acoustic energy is the opposite. Moreover, the greater the pressure wave (P-wave) speed in the sea bottom, the more acoustic energy remains in the water rather than leaking into the bottom; the influence laws of the density and the shear wave (S-wave) speed in the sea bottom are opposite.

Bayesian Inversion for Geoacoustic Parameters in Shallow Sea.

Geoacoustic parameter inversion is a crucial issue in underwater acoustic research for shallow sea environments and has increasingly become popular in the recent past. This paper investigates the geoacoustic parameters in a shallow sea environment using a single-receiver geoacoustic inversion method based on Bayesian theory. In this context, the seabed is regarded as an elastic medium, the acoustic pressure at different positions under low-frequency is chosen as the study object, and the theoretical prediction value of the acoustic pressure is described by the Fast Field Method (FFM). The cost function between the measured and modeled acoustic fields is established under the assumption of Gaussian data errors using Bayesian methodology. The Bayesian inversion method enables the inference of the seabed geoacoustic parameters from the experimental data, including the optimal estimates of these parameters, such as density, sound speed and sound speed attenuation, and quantitative uncertainty estimates. The optimization is carried out by simulated annealing (SA), and the Posterior Probability Density (PPD) is given as the inversion result based on the Gibbs Sampler (GS) algorithm. Inversion results of the experimental data are in good agreement with both measured values and estimates from Genetic Algorithm (GA) inversion result in the same environment. Furthermore, the results also indicate that the sound speed and density in the seabed have fewer uncertainties and are more sensitive to acoustic pressure than the sound speed attenuation. The sea noise could increase the variance of PPD, which has less influence on the sensitive parameters. The mean value of PPD could still reflect the true values of geoacoustic parameters in simulation.

Value of whole-body dynamic 18F-FMISO PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid on C6 rat gliomas.

The purpose of this study was to investigate the value of tumour-to-muscle (T/M) ratios and Patlak Ki images extracted from whole-body dynamic 18F-fluoromisonidazole (FMISO) PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid (OA). Twenty-four rats with C6 gliomas were divided into 4 groups and treated with OA (group B), radiotherapy (group C), both (group D) or neither (group A). Whole-body dynamic 18F-FMISO PET/CT scans were performed for 120 min before treatment and 24 h following the treatment course. The tumour samples were dissected for hematoxylin and eosin staining, and HIF-1α, Ki-67 and GLUT-1 immunohistochemical staining. PET images were analysed using kinetic modelling (Patlak Ki) and static analysis (T/M ratios), and correlated with immunohistochemical results. The changes in T/M ratios, Ki values and tumour volume before treatment and 24 h following the treatment course were compared, and the survival time of tumour-bearing rats was recorded. Kaplan-Meier analysis showed that OA combined with radiotherapy can inhibit tumour growth and prolong the survival time of tumour-bearing rats. Whole-body dynamic 18F-FMISO PET/CT showed that the Ki values in group D were significantly lower than those in group C, whilst there was no significant difference in T/M ratios between groups C and D. The Pearson correlation coefficient analysis showed that Ki values were significantly related to immunohistochemical results. Our study suggests that Patlak Ki images may add value to PET/CT static images for evaluating the early radio-sensitizing effect of OA.

A case report of old injury of lateral collateral ligament of knee joint combined with injury of common peroneal nerve.

Since common peroneal nerve is easy be injured because of superficial position of caput fibulae, less surrounding soft tissue and poor mobility, injury of common peroneal nerve is a problem worth discussing in the field of trauma orthopedics. Common peroneal nerve injury often causes foot prolapse, inability in dorsiflexion and eversion, sensory disturbance of anterolateral side of the lower leg and dorsum of foot. In this article, a case of old injury of lateral collateral ligament of knee joint combined with an avulsion fracture of fibular head resulting in injury of common peroneal nerve was reported and repaired by surgery with good effects.

Luminol functionalized tin dioxide nanoparticles with catalytic effect for sensitive detection of glucose and uric acid.

In this work, novel luminol functionalized nanoparticles (SnO2@Luminol NPs) with mesoporous spherical structure were synthesized by a simple and green method, which exhibited good chemiluminescence (CL) intensity without any additional catalysts. In addition, the CL intensities generated by SnO2@Luminol/H2O2 system were linearly related to the logarithm values of H2O2 concentrations, and CL mechanism of SnO2@Luminol/H2O2 system was investigated. On this basis, a sensitive CL method was proposed to determine glucose and uric acid. The fabricated CL method displayed wide linear ranges (glucose, 1.0 × 10-8 - 1.0 × 10-4 M; uric acid, 1.0 × 10-8 - 1.0 × 10-4 M) and low detection limits (glucose, 5.4 nM; uric acid, 6.8 nM). The proposed CL method achieved sensitive and specific glucose and uric acid detection in human serum specimens, and the measured results were consistent with the clinical diagnosis. Furthermore, as long as the product of reaction between enzyme and substrate is H2O2, this CL method can also be extended to other biological detection fields.

Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT.

The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16-1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients.

A novel polydopamine-modified metal organic frameworks catalyst with enhanced catalytic performance for efficient degradation of sulfamethoxazole in wastewater.

In this study, a novel polydopamine (PDA)-modified metal organic frameworks (MOFs) catalyst (MIL/PDA) was successfully fabricated to activate persulfate (PS) for the degradation of sulfamethoxazole (SMX) in wastewater. The experimental results indicated that PDA-modified catalyst exhibited superior catalytic performance and enhanced the degradation of SMX (91.5%) compared to pure MOFs. The physical-chemical properties of the MIL/PDA catalyst were comprehensively characterized, and the applications in the catalytic degradation of SMX were evaluated. It was found that the modification of PDA enhanced the electron transfer, while promoting the redox cycle of Fe(III)/Fe(II), which in turn boosted the production of active oxygen species. Furthermore, MIL/PDA showed high stability and reusable performance over multiple cycles. Both radical and non-radical pathways were jointly involved in the activation process of PS were confirmed by quenching experiments combined with electron paramagnetic resonance (EPR). Based on this, the possible mechanism of the catalytic reaction was investigated. Finally, five degradation pathways of SMX degradation were proposed according to the results of liquid chromatography-mass spectrometry (LC-MS). This work provided a new insight into the design of novel and efficient heterogeneous catalysts for advanced wastewater treatment.

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study.

Purpose: Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods: Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results: We found that MA could down-regulate the IL-1ß-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1ß. Moreover, MA protects chondrocytes from IL-1ß-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1ß-induced chondrocytes. Conclusion: These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

18F-FDG Micro PET/CT imaging to evaluate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity.

OBJECTIVE: Radioresistance of tumor cells is a major factor associated with failure of radiotherapy (RT). This study aimed to investigate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity. MATERIALS AND METHODS: Short hairpin RNA (shRNA) was used to knockdown BRCA1 gene in MDA-MB231 cells. Cell viability and proliferative capacity were assessed by CCK-8 and colony formation assays, respectively. We established xenograft models in nude mice to evaluate tumor volume and tumor weight. The mice were imaged by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) before and after RT to evaluate changes in maximum standardized uptake value (SUVmax) and tumor SUVmax/muscle SUVmax (TMR). Changes in HIF-1α, Glut-1 and Ki-67 were analyzed and the correlation between 18F-FDG uptake and tumor biology was analyzed. RESULTS: Compared with the control cells, RT significantly reduced cell viability and colony formation capacity in cells with the BRCA1 gene knockdown. In vivo assays showed that there was obvious delay in the tumor growth in the shBRCA1+RT group compared with the control group. 18F-FDG Micro PET/CT indicated a reduction in glucose metabolism in the shBRCA1+RT group, with statistically significant differences in both the SUVmax and TMR. The data showed the expression of HIF-1α, Glut-1 and Ki-67 was downregulated in the shBRCA1+RT group, and both SUVmax and TMR had significant correlation with tumor biology. CONCLUSION: These results demonstrated that BRCA1 knockdown improves the sensitivity of MDA-MB231 breast cancer cells to RT. In addition, 18F-FDG PET/CT imaging allows non-invasive analysis of tumor biology and assessment of radiosensitivity.

Electrocatalytic oxidation of ciprofloxacin by Co-Ce-Zr/γ-Al2O3 three-dimensional particle electrode.

In this work, Co-Ce-Zr/γ-Al2O33 particle electrodes were prepared for the efficient degradation of ciprofloxacin (CIP). Co-Ce-Zr/γ-Al2O3 particle electrodes were analyzed with a scanning electron microscope (SEM), X-Ray Diffraction (XRD), X-Ray Fluorescence Spectrometer (XRF), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). According to the results, significant amounts of Co3O4, CeO2, and ZrO2 were formed on the Co-Ce-Zr/γ-Al2O3 particle electrodes. It was shown that when the conditions of the reaction system were at pH=6, conductivity of 4 ms/cm, current of 0.2 A, initial pollutant concentration of 100 mg/L, and material dosage of 15 g, CIP could be completely degraded within 40 min, and the energy consumed in the reaction was 41.3 kWh/kg CIP. The rate of total organic carbon (TOC) removal by Co-Ce-Zr/γ-Al2O3 particle electrodes was recorded to be approximately 52.6%. Using a response surface methodology, we explored the optimal operating conditions. At the same time, we also explored the influence of inorganic anions in water and actual water medium on the rate of CIP removal. In addition, the ESR data proved that the main active substance in the reaction system was ·OH. The degradation intermediates were investigated, and the possible mechanism was proposed. Thus, this research provided a new solution for the treatment of antibiotic-containing wastewater.

Application of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in Predicting and Monitoring Early Efficacy of Anti-Angiogenic Therapy in the C6 Glioma Rat Model.

OBJECTIVE: To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in evaluating early effects of anti-angiogenic therapy in the C6 glioma rat model. METHODS: Twenty-six rats of the C6 glioma model were randomly divided into a treatment group (received bevacizumab) and a control group (physiological saline). IVIM-DWI was performed on days 0, 1, 3, 5, and 7 after anti-angiogenic therapy and tumor growth and IVIM-DWI parameters were dynamically observed. Hematoxylin and eosin, CD34 microvessel density (MVD), proliferation of cell nuclear antigen (PCNA), and Hif-α staining were performed on day 7. One-way ANOVA was used to compare intra-group differences and an independent-samples t-test was used to compare inter-group differences of MRI parameters. Correlations between IVIM-DWI parameters, tumor size, and pathological results were analyzed. RESULTS: The relative change in tumor volume (ΔVolume) in the two groups differed significantly on days 5 and 7 (p = 0.038 and p < 0.001). The perfusion-related parameters D*- and f-values decreased in the treatment group and demonstrated significant differences compared with the control group on days 3, 5, and 7 (p = 0.033, p < 0.001, and p < 0.001, respectively). The diffusion-related parameters ADC and D-values increased in the treatment group and were found to be significantly differently different from the control group on days 5 and 7 (both p < 0.001). The initial D-value showed a negative correlation with ΔVolume (γ = -0.744, p < 0.001), whereas the initial D*-value and relative change of D-value had a positive correlation with ΔVolume (γ = 0.718, p < 0.001 and γ = 0.800, p < 0.001, respectively). MVD was strongly positively correlated with D*-value (r = 0.886, p = 0.019), PCNA was negatively correlated with ADC- and D-values (r = -0.848, p = 0.033; and r = -0.928 p = 0.008, respectively), and Hif-1α was strongly negatively correlated with D*-value (r = -0.879, p = 0.010). CONCLUSION: IVIM-DWI was sensitive and accurate in predicting and monitoring the effects of early anti-angiogenesis therapy in a C6 glioma rat model.

The Incremental Prognostic Value of Baseline 18F-FDG PET/CT Imaging in Angioimmunoblastic T-Cell Lymphoma.

METHODS: From January 2010 to October 2019, a total of 23 patients who pathologically confirmed to have AITL were retrospectively analyzed. All patients underwent whole-body 18F-FDG PET/CT scan before chemotherapy. The 18F-FDG PET/CT features, clinical data, laboratory indicators, Ki67 labeling index, and survival status were collected and analyzed. RESULTS: The median follow-up was 22 months. The expected 1-, 2-, and 3-year survival rate was 72.2%, 49.6%, and 42.5%, respectively. The median overall survival (OS) was 23 months (95% confidence interval (CI): 8.459~37.541). AITL is prone to extranodal infiltration, in addition to nodal infiltration (6 patients had nodal infiltration alone, and 17 patients had both nodal and extranodal infiltration). The SUVmax of nodal lesions were higher than that for the extranodal lesions (10.43 ± 4.45, 6.64 ± 3.51, F = 2.78, t = 4.39, P < 0.01). On multivariate survival analysis, the Eastern Cooperative Oncology Group (ECOG) and SUVmax of extranodal lesions were independent predictors of OS. CONCLUSION: Baseline 18F-FDG PET/CT results and SUVmax of extranodal lesions showed an incremental prognostic value in addition to clinical prognostic factors.

Evaluation of Tumor Hypoxia in C6 Glioma Rat Model With Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To investigate the feasibility of determining quantitative parameters for evaluating tumor hypoxia in the C6 glioma model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were inoculated to establish C6 brain glioma models. DCE-MRI scans were performed 14, 21, and 28 days after transplantation. Quantitative parameters comprising Ktrans, Ve, Kep, and Vp were calculated and analyzed. At the end of each scan, 10 rats were randomly selected for immunohistochemical (IHC) staining of hypoxia-inducible factor-17αl (HIF-1α), proliferating cell nuclear antigen (PCNA), and CD34. Correlations between quantitative parameters and IHC scores were analyzed. RESULTS: The tumor volumes increased with time. The Ktrans values on days 14, 21, and 28 were 0.03 ± 0.009 min-1, 0.084 ± 0.010 min-1, and 0.050 ± 0.016 min-1, while the Ve values were 0.17 ± 0.070, 0.46 ± 0.159, and 0.51 ± 0.193, the Kep values were 0.18 ± 0.070%, 0.220 ± 0.049%, and 0.06 ± 0.035%, and these three parameters all differed significantly among the three time points. The Vp values on days 14, 21, and 28 were 0.09 ± 0.040%, 0.120 ± 0.034%, and 0.06 ± 0.010%, but the values did not differ among the three time points (P = 0.073). Ktrans had significant negative correlations with the HIF-1α scores on days 14 and 21 when there was also a positive correlation between Ktrans and CD34. Ve had negative correlations with the HIF-1α score on days 14 and 21, and there was a negative correlation between Ve and PCNA on day 21. Kep had a negative correlation with the HIF-1α score and a positive correlation with MVD on day 21. CONCLUSIONS: DCE-MRI may be a useful method for the noninvasive evaluation of the hypoxia status in a glioma model.

Hypoxia Imaging and Biological Evaluation of the Radiosensitizing Effect of Oleanolic Acid.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the radiosensitizing effect of oleanolic acid (OA) on C6 rat glioma and the changes in tumor biology during radiosensitization therapy on 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT). METHODS: The radiosensitizing effect of OA on C6 tumors was assessed in vivo by measuring the tumor inhibitory rate and rat survival time. Meanwhile, rats with C6 tumors were imaged with 18F-FMISO PET/CT during radiosensitization therapy. Tumor-to-muscle ratio (TMR) of 18F-FMISO maximum uptake was calculated by region of interest analysis. Changes in tumor biology after therapy were assessed with immunohistochemical staining. 18F-FMISO uptake was analyzed in relation to expression of tumor biomarkers including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut-1), the proliferation antigen Ki67, tumor suppressor P53, and microvessel density (MVD). RESULTS: The results showed that OA combined with radiation inhibited the growth rates of tumors and prolonged the survival period of tumor-bearing rats effectively (χ2 = 12.5, p < 0.01). 18F-FMISO PET/CT indicated decreases in hypoxia after radiosensitization therapy. Statistical differences were observed in TMR of the irradiation group and OA combined with irradiation group (t = 3.32, p < 0.05). HIF-1α, Glut-1, Ki67, P53, and MVD expressions in tumors were downregulated by OA combined with radiation as well as with radiation alone. Additionally, there was a significant positive linear correlation between TMR and HIF-1α, Glut-1, Ki67, P53, and MVD. CONCLUSIONS: These results suggest that OA has a radiosensitizing effect on C6 tumors in terms of tumor volume inhibition, survival extension, and multiple poor prognosis biological markers downregulation. 18F-FMISO PET/CT can be of value for tumor biology noninvasive capture and radiosensitization response evaluation.

Radiosensitizing effect of irisquinone on glioma through the downregulation of HIF-1α evaluated by 18F-FDG and 18F-FMISO PET/CT.

OBJECTIVE: The aim of this study was to elucidate the radiosensitizing mechanism of irisquinone (IQ) and evaluate the utility of F-fluorodeoxyglucose (F-FDG) and F-fluoromisonidazole (F-FMISO) PET/computed tomography (CT) in assessing the radiosensitizing effect of IQ. MATERIALS AND METHODS: In an in-vitro experiment, C6 rat glioma cells were treated with IQ, radiation, or both. The viability and radiosensitivity of C6 cells were detected using the MTT assay and clonogenic survival assay. The expression of hypoxia-inducible factor-1α (HIF-1α) was evaluated by real-time PCR and western blot. In an in-vivo experiment, C6 rat glioma cells were implanted into the right flank of rats and treated with IQ, radiation, both, or no treatment. F-FDG and F-FMISO PET/CT images were obtained before and after treatment. The expression of HIF-1α was detected by immunohistochemistry staining. RESULTS: In the in-vitro experiment, the results of the MTT assay showed that the half-inhibition concentration (IC50) of IQ for normoxic and hypoxic C6 tumor cells was 17.2 and 21.0 nmol/l, respectively. Clonogenic survival assay showed that IQ could improve the radiosensitivity of both normoxic and hypoxic C6 tumor cells. When the concentration of irradiation was 20% IC50 (4.2 nmol/l), the sensitive enhancement ratio of normoxic and hypoxic C6 tumor cells was 1.18 and 1.33, respectively. The mRNA and protein expression levels of HIF-1α decreased significantly when treated with IQ plus radiation compared with the other groups.In the in-vivo experiment, 24 or 48 h after different treatments, the maximum standardized uptake values (SUVmax) of F-FDG or F-FMISO uptake decreased in the radiation group and the IQ plus radiation group, whereas these values increased in the control and IQ groups. The SUVmax of F-FDG or F-FMISO uptake in IQ plus radiation group were lower than those of the radiation group (t=3.28, 2.62, P<0.05). However, there was no significant decrease in tumor volumes in the radiation group and the IQ plus radiation treatment group early after treatment.Immunohistochemistry staining showed that there were significant differences in the expression of HIF-1α in the four groups (F=87.1, P<0.01). The SUVmax of both F-FDG and F-FMISO uptake showed a significant correlation with the expression of HIF-1α. F-FMISO provided a higher correlation coefficient with HIF-1α than F-FDG (r=0.93, 0.82, P<0.01). CONCLUSION: The present experiments indicated that IQ enhanced the radiosensitivity of C6 rat glioma cells both in vitro and in vivo. The primary mechanism of this radiosensitizing effect involves the downregulation of HIF-1α. F-FDG and F-FMISO PET/CT were sensitive and noninvasive for monitoring the early radiosensitizing effect of IQ. Meanwhile, F-FMISO PET/CT provided more information on the changes in tumor hypoxic status.

Fluorine-18-deoxyglucose positron emission tomography/computed tomography with Ki67 and GLUT-1 immunohistochemistry for evaluation of the radiosensitization effect of oleanolic acid on C6 rat gliomas.

OBJECTIVE: The aim of this study was to investigate the radiosensitization effect of oleanolic acid (OA) in an in-vivo C6 rat glioma model using fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) and Ki67 and glucose transporter-1 (GLUT-1) immunohistochemistry(IHC) and evaluate the utility of 18F-FDG PET/CT in assessing early changes after radiotherapy. MATERIALS AND METHODS: Tumor-bearing rats were divided into four groups: the control group (group A), the OA group(group B), the radiotherapy group (group C), and the OA combined with radiotherapy group (group D). 18F-FDG PET/CT images were obtained to monitor the tumor/muscle (T/M) ratio of 18F-FDG uptake before treatment,1 day after treatment, and 7 days after treatment. Tumor volume changes were also assessed, and hematoxylin and eosin staining and Ki67 and GLUT-1 IHC staining were also carried out. RESULTS: Before treatment, there were no obvious differences between the T/M ratios (F=0.147, P=0.931)and tumor volumes (F=0.177, P=0.911) among the four groups. At day 1 after treatment, statistical differences were observed in the T/M ratios (F=2.891, P=0.05), with decreased values in groups C and D compared with group A(tCA=2.354, tDA=2.356, P<0.05). At day 7 after treatment,the T/M values of group D were lower than those of the other three groups (tDC=2.416, P=0.03; tDA=8.133,tDB=7.656, P<0.01), and the tumor volumes of group D were significantly decreased compared with group C(t=2.351, P=0.02). There were significant differences in tumor cell densities and in the expression of Ki67 and GLUT-1 in the four groups (F=16.667, 22.082, and 39.555,P<0.001). The T/M ratio showed a significant correlation with the expression of Ki67 and GLUT-1, and our study also found a significant relationship between the expression of Ki67 and the expression of GLUT-1. CONCLUSION: OA has a radiosensitization effect on C6 rat glioma tumors in vivo, detected using 18F-FDG PET/CT and Ki67 and GLUT-1 IHC staining. 18F-FDG PET/CT is a potentially sensitive tool for the evaluation of early changes after radiotherapy.