Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/ß-catenin signaling pathways.

Osteosarcoma (OS) is the most prevalent malignant bone tumor with poor prognosis. Developing new drugs for the chemotherapy of OS has been a focal point and a major obstacle of OS treatment. Nitazoxanide (NTZ), a conventional anti-parasitic agent, has got increasingly noticed because of its favorable antitumor potential. Herein, we investigated the effect of NTZ on human OS cells in vitro and in vivo. The results obtained in vitro showed that NTZ inhibited the proliferation, migration and invasion, arrested cell cycle at G1 phase, while induced apoptosis of OS cells. Mechanistically, NTZ suppressed the activity of AKT/mTOR and Wnt/ß-catenin signaling pathways of OS cells. Consistent with the results in vitro, orthotopic implantation model of 143B OS cells further confirmed that NTZ inhibited OS cells growth and lung metastasis in vivo. Notably, NTZ caused no apparent damage to normal cells/tissues. In conclusion, NTZ may inhibit tumor growth and metastasis of human OS cells through suppressing AKT/mTOR and Wnt/ß-catenin signaling pathways.

Clinical effectiveness of contrast medium injection protocols for 80-kV coronary and craniocervical CT angiography-a prospective multicenter observational study.

BACKGROUND AND OBJECTIVE: Decreasing X-ray tube voltage is an effective way to reduce radiation and contrast dose, especially in non-obese patients. The current study focuses on CTA in non-obese patients to evaluate image quality and feasibility of 80-kV acquisition protocols with varying iodine delivery rates (IDR) and contrast concentrations in routine clinical practice. METHODS: A prospective observational study in patients ≥ 18 years and ≤ 90 kg referred for coronary or craniocervical CTA at 10 centers in China (ClinicalTrials.gov: NCT02840903). Patients were divided into four groups: a standard 100-kV protocol (370 mgI/ml, IDR 1.48 gI/s), and three 80-kV protocols (370 mgI/ml, IDR 1.2 gI/s; 300 mgI/ml, IDR 1.2 gI/s; 300 mgI/ml, IDR 0.96gI/s). The primary outcome was contrast opacification of target vascular segments. Secondary outcomes were image quality (contrast-to-noise ratio, signal-to-noise ratio, visual image quality, and diagnostic confidence assessment), radiation, and iodine dose. RESULTS: From July 2016 to July 2017, 1213 patients were enrolled: 614 coronary and 599 craniocervical CTA. The mean contrast opacification was ≥ 300 HU for 80-kV 1.2 gI/s IDR scanned segments; IDR 0.96 gI/s led to lower opacification. Image quality and diagnostic confidence were fair to excellent (≥ 98% of images), despite lower contrast-to-noise ratios and signal-to-noise ratios in 80-kV images. Compared to the standard protocol, 80-kV protocols led to 44-52% radiation dose reductions (p < 0.001) and 19% iodine dose reductions (p < 0.001). CONCLUSION: Eighty-kilovolt 1.2 gI/s IDR protocols can be recommended for coronary and craniocervical CTA in non-obese patients, reducing radiation and iodine dose without compromising image quality. KEY POINTS: • Using low-voltage scanning CTA protocols, in which tube voltage and iodine delivery rate are reduced proportionally (voltage: 80 kV, IDR: 1.2 gI/s), reduces radiation and contrast dose without compromising image quality in routine clinical practice. • Reducing iodine delivery rate beyond direct proportionality to tube voltage is not beneficial.

Potentialities of multi-b-values diffusion-weighted imaging for predicting efficacy of concurrent chemoradiotherapy in cervical cancer patients.

BACKGROUND: To testify whether multi-b-values diffusion-weighted imaging (DWI) can be used to ultra-early predict treatment response of concurrent chemoradiotherapy (CCRT) in cervical cancer patients and to assess the predictive ability of concerning parameters. METHODS: Fifty-three patients with biopsy proved cervical cancer were retrospectively recruited in this study. All patients underwent pelvic multi-b-values DWI before and at the 3rd day during treatment. The apparent diffusion coefficient (ADC), true diffusion coefficient (Dslow), perfusion-related pseudo-diffusion coefficient (Dfast), perfusion fraction (f), distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index(α) were generated by mono-exponential, bi-exponential and stretched exponential models. Treatment response was assessed based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 1 month after the completion of whole CCRT. Parameters were compared using independent t test or Mann-Whitney U test as appropriate. Receiver operating characteristic (ROC) curves was used for statistical evaluations. RESULTS: ADC-T0 (p = 0.02), Dslow-T0 (p <  0.01), DDC-T0 (p = 0.03), ADC-T1 (p <  0.01), Dslow-T1 (p <  0.01), ΔADC (p = 0.04) and Δα (p <  0.01) were significant lower in non-CR group patients. ROC analyses showed that ADC-T1 and Δα exhibited high prediction value, with area under the curves of 0.880 and 0.869, respectively. CONCLUSIONS: Multi-b-values DWI can be used as a noninvasive technique to assess and predict treatment response in cervical cancer patients at the 3rd day of CCRT. ADC-T1 and Δα can be used to differentiate good responders from poor responders.

Apparent Diffusion Coefficient and Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Pancreatic Cancer: Characteristics and Correlation With Histopathologic Parameters.

OBJECTIVE: To clarify diffusion and perfusion abnormalities and evaluate correlation between apparent diffusion coefficient (ADC), MR perfusion and histopathologic parameters of pancreatic cancer (PC). METHODS: Eighteen patients with PC underwent diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Parameters of DCE-MRI and ADC of cancer and non-cancerous tissue were compared. Correlation between the rate constant that represents transfer of contrast agent from the arterial blood into the extravascular extracellular space (K, volume of the extravascular extracellular space per unit volume of tissue (Ve), and ADC of PC and histopathologic parameters were analyzed. RESULTS: The rate constant that represents transfer of contrast agent from the extravascular extracellular space into blood plasma, K, tissue volume fraction occupied by vascular space, and ADC of PC were significantly lower than nontumoral pancreases. Ve of PC was significantly higher than that of nontumoral pancreas. Apparent diffusion coefficient and K values of PC were negatively correlated to fibrosis content and fibroblast activation protein staining score. Fibrosis content was positively correlated to Ve. CONCLUSION: Apparent diffusion coefficient values and parameters of DCE-MRI can differentiate PC from nontumoral pancreases. There are correlations between ADC, K, Ve, and fibrosis content of PC. Fibroblast activation protein staining score of PC is negatively correlated to ADC and K. Apparent diffusion coefficient, K, and Ve may be feasible to predict prognosis of PC.

Transluminal attenuation gradient in coronary computed tomography angiography for determining stenosis severity of calcified coronary artery: a primary study with dual-source CT.

OBJECTIVES: To evaluate the diagnostic accuracy of transluminal attenuation gradient (TAG) for stenosis severity of calcified lesions assessed by coronary computed tomography angiography (CCTA). METHODS: One hundred seven patients who underwent CCTA and coronary angiography (CAG) were enrolled. TAGs of 309 major epicardial coronary arteries were measured. The impact of plaque composition, Agatston scores, and lesion length ratio on TAG were analyzed. Diagnostic performance vs. CAG of TAG, CCTA, and combined TAG/CCTA were evaluated, and incremental value of TAG for reclassification of CCTA stenosis severity in calcified lesions was also analyzed. RESULTS: TAG decreased consistently with stenosis severity. TAG was significantly lower in coronary arteries with calcification scores >300 and lesion length ratios >2/3. TAG improved diagnostic accuracy of CCTA (c-statistic =0.982 vs. 0.942, P = 0.0001) in calcified lesions, and the sensitivity, specificity, positive, and negative predictive values of TAG cutoff ≤ -11.33 were 72 %, 91 %, 88 %, and 78 %, respectively. The addition of TAG to CCTA resulted in significant reclassification (NRI =0.093, P = 0.022) in calcified vessels. CONCLUSIONS: Measurement of TAG may improve diagnostic performance and reclassification of CCTA in coronary stenosis caused by calcified lesions. KEY POINTS: • TAG decreased as calcification scores and lesion length increased. • TAG markedly improved the diagnostic performance of CCTA for calcified lesions. • TAG improved reclassification of coronary artery stenosis severity in CCTA.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.

Neurological prognosis in surgically treated acute aortic dissection with brain computed tomography perfusion.

OBJECTIVES: The aim of this study was to explore the prognostic value of brain computed tomography perfusion (CTP) for postoperative new stroke in acute type A aortic dissection (ATAAD) patients. METHODS: Patients with ATAAD and suspected cerebral malperfusion who underwent brain CTP and surgical repair were retrospectively analysed. Brain perfusion was quantified mainly with the averaged cerebral blood flow. Significant clinical and imaging findings were identified through univariable and multivariable regression analysis. Furthermore, the added prognostic benefit of perfusion parameters was confirmed with the receiver operating characteristic curves in the entire cohort and subgroup analysis. RESULTS: The incidence of postoperative new stroke was 30.8% (44/143). The independent adjusted predictors of postoperative new stroke included an impaired averaged cerebral blood flow (ml/100 ml/min) (odds ratio: 0.889; P < 0.001), severe stenosis (odds ratio: 5.218; P = 0.011) or occlusion (odds ratio: 14.697; P = 0.048) of the true lumen in common carotid artery (CCA), hypotension on admission (odds ratio: 9.644; P = 0.016) and a longer surgery time (odds ratio: 1.593; P = 0.021). The area under the receiver operating characteristic curves significantly improved after adding perfusion parameters to clinical and computed tomography angiography characteristics (P = 0.048). This benefit was more pronounced in patients with severe stenosis or occlusion in CCA true lumen (P = 0.004). CONCLUSIONS: Brain CTP could be a useful prognostic tool for surgically treated ATAAD patients and especially beneficial in patients with severe stenosis or occlusion of the CCA true lumen.

T(2)-weighted combined with diffusion-weighted images for evaluating prostatic transition zone tumors at 3 Tesla.

AIM: We hypothesize that the combination of T(2)-weighted (T(2)W) MRI with diffusion-weighted imaging (DWI) methods provides a powerful clinical application for the differential diagnosis of prostate cancer and benign lesion in the prostatic transition zone (TZ). METHODS: This retrospective study included 113 patients who were diagnosed with TZ lesions by MRI. The apparent diffusion coefficient values were compared between biopsy-proven benign and malignant lesions. RESULTS: The apparent diffusion coefficient values for the malignant nodules were significantly lower than those of the benign nodules. The area under the curve values for T(2)W imaging combined with DWI and T(2)W imaging alone were 0.991 and 0.884, respectively. CONCLUSION: T(2)W combined with DWI provides a powerful tool for noninvasive differentiation between malignant and benign prostatic hyperplasia nodules in the prostatic TZ.

Dynamic contrast-enhanced MR imaging in a phase â ¡ study on neoadjuvant chemotherapy combining Rh-endostatin with docetaxel and epirubicin for locally advanced breast cancer.

BACKGROUND: Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients. METHODS: The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery. RESULTS: The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and K(trans) (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with K(trans) after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00). CONCLUSIONS: The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and K(trans), could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.

Alantolactone Inhibits Melanoma Cell Culture Viability and Migration and Promotes Apoptosis by Inhibiting Wnt/ß-Catenin Signaling.

BACKGROUND: Melanoma is a highly invasive and metastatic malignant tumor originating from melanocytes and is associated with a poor prognosis. Surgical resection and chemotherapy are currently the main therapeutic options for malignant melanoma; however, their efficacy is poor, highlighting the need for the development of new, safe, and effective drugs for the treatment of this cancer. OBJECTIVE: To investigate the effects of alantolactone (ALT) on the proliferative, migratory, invasive, and apoptotic ability of malignant melanoma cells and explore its potential anticancer mechanism. METHODS: Melanoma cells (A375 and B16) were treated with different concentrations (4, 6, 8, and 10 µmol/L) of ALT, with DMSO and no treatment serving as controls. The effects of the different concentrations of the drug on cell proliferation were assessed by crystal violet staining and CCK-8 assay. The effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively. Flow cytometry was used to evaluate the effects of the drug on apoptosis and the cell cycle. ALT target genes in melanoma were screened using network pharmacology. Western blotting was used to measure the expression levels of the proliferation-related protein PCNA; the apoptosisrelated proteins Bax, Bcl-2, and caspase-3; the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, vimentin, E-cadherin, and N-cadherin; and the canonical Wnt signaling pathway-related proteins ß-catenin, c-Myc, and p-GSK3ß. In addition, an l model of melanoma was established by the subcutaneous injection of A375 melanoma cells into nude mice, following which the effects of ALT treatment on malignant melanoma were determined in vivo. RESULTS: Compared with the controls, the proliferative, migratory, and invasive capacity of ALT-treated melanoma cells was significantly inhibited, whereas apoptosis was enhanced (P<0.01), showing effects that were exerted in a dose-dependent manner. The expression levels of the pro-apoptotic proteins Bax and caspase-3, as well as those of the interstitial marker E-cadherin, were upregulated in melanoma cells irrespective of the ALT concentration (P<0.05). In contrast, the expression levels of the anti-apoptotic protein Bcl-2, the proliferation-related protein PCNA, and the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, N-cadherin, and vimentin were downregulated (P<0.05). The network pharmacology results indicated that GSK3ß may be a key ALT target in melanoma. Meanwhile, western blotting assays showed that ALT treatment markedly suppressed the expression of ß-catenin as well as that of its downstream effector c-Myc, and could also inhibit GSK3ß phosphorylation. CONCLUSION: ALT can effectively inhibit the culture viability, migration, and invasion of A375 and B16 melanoma cells while also promoting their apoptosis. ALT may exert its anti-melanoma effects by inhibiting the Wnt/ß-catenin signaling pathway. Combined, our data indicate that ALT has the potential as an effective and safe therapeutic drug for the treatment of melanoma.

Corrigendum to 'Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/ß-catenin and MAPKs signaling pathways' [Genes & Diseases 9 (2022) 466-478].

[This corrects the article DOI: 10.1016/j.gendis.2020.07.014.].

A new comprehensive evaluation indicator of adsorbent for gas separation.

To evaluate and compare the performances of different adsorbents for gas separation, an adsorbent comprehensive evaluation indicator (ACEI) is proposed. In the ACEI, the working capacity, selectivity, adsorption rate, regeneration and circulation parameters, stability during adsorption, and tolerance to impurities are considered, and some exponents are introduced to allow the ACEI to adapt to different adsorbent working conditions. To illustrate the applicability of the ACEI, the adsorption of CO2 and N2 was investigated on two kinds of activated carbons (ACs), which were used for gas purification and bulk separation. The ACEI is a better overall indicator than other currently used indicators to evaluate the performance of adsorbents.

Predictive Value of CT-Based Radiomics in Distinguishing Renal Angiomyolipomas with Minimal Fat from Other Renal Tumors.

Objectives: This study is aimed at determining whether CT-based radiomics models can help differentiate renal angiomyolipomas with minimal fat (AMLmf) from other solid renal tumors. Methods: This retrospective study included 58 patients with a postoperative pathologically confirmed AMLmf (observation group) and 140 patients with other common renal tumors (control group). Non-contrast-enhanced CT and contrast-enhanced CT data were evaluated. Radiomics features were extracted from manually delineated volume of interest (VOIs). The least absolute shrinkage and selection operator (LASSO) regression was used for feature screening. Five classifiers, including logistic regression, multilayer perceptron (MLP), support vector machine (SVM), k-nearest neighbor (KNN), and logistic regression (LR), were used, with leave-out validation (128 training, 60 testing). The diagnostic performance of the classifier was evaluated and compared by receiver operating characteristic curve (ROC) analysis. Results: Among the 1029 extracted features, prediction models of AMLmf were composed, by 2, 10, 4, and 9 selected features for precontrast phase (PCP), corticomedullary phase (CMP), nephrographic phase (NP), and excretory phase (EP), respectively. Models of CMP and NP achieved adequate performance after using MLP classifier, with prediction accuracy of 0.767 (AUC 0.85, sensitivity 0.76, and specificity 0.78) and 0.783 (AUC 0.83, sensitivity 0.79, and specificity 0.78), respectively. MLP model of features selected from the combination of the all features had the best diagnostic performance (accuracy 0.8500, sensitivity 0.8095, specificity 0.9444, and AUC 0.9193). Conclusions: Radiomics features may help to distinguish benign AMLmf from common malignant kidney masses, which may contribute to the selection of interventions for renal tumors.

Schisandrin B suppresses osteosarcoma lung metastasis in vivo by inhibiting the activation of the Wnt/ß­catenin and PI3K/Akt signaling pathways.

Osteosarcoma (OS) is the most common malignant bone tumor worldwide and is associated with a poor prognosis, often being accompanied by lung metastasis at an early stage. At present, there are several side­effects associated with the OS clinical treatment of OS, with the treatment effects often being unsatisfactory. Thus, there is an urgent need for the development of safe and effective novel drugs for the treatment of OS. Schisandrin B (Sch B) has been previously demonstrated to exhibit antitumor properties. The present study was focused on the effects of Sch B on OS cells (143B, MG63, Saos2 and U2OS) in vitro and in vivo, and also on its possible antitumor mechanisms. In cell experiments, it was revealed that Sch B inhibited OS cell proliferation, migration and invasion, and increased OS cell apoptosis. As regards its biosafety, no notable effects of Sch B on the vitality of normal cells were observed. Mechanistically, it was demonstrated that Sch B blocked OS cell proliferation in the G1 phase. Subsequently, by using established animal models, it was revealed that Sch B significantly inhibited OS growth and lung metastasis in vivo. In summary, the results of the present study revealed that Sch B inhibited OS cell proliferation, migration and invasion, and promoted apoptosis via the inhibition of the Wnt/ß­catenin and PI3K/Akt signaling pathways, without causing any noticeable toxic effects on healthy cells at the therapeutic concentrations used. These findings suggest that Sch B has potential for use as a novel agent for the clinical treatment of OS.

Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/ß-catenin and MAPKs signaling pathways.

Although there are many therapeutic strategies such as surgery and chemotherapy, the prognosis of osteosarcoma (OS) is still far from being satisfactory. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. In the present study, we investigated the anti-OS activity of Alantolactone (ALT), a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium, and probed the possible mechanism involved. We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells. Then, we validated that ALT reduced migration, decreased invasion possibly through reversing epithelial mesenchymal transition (EMT) process and suppressing Matrix metalloproteinases (MMPs). Moreover, we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro. In addition, we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo. Mechanistically, ALT inhibited the activity of Wnt/ß-catenin and p38, ERK1/2 and JNK Mitogen Activated Protein Kinases (MAPKs) signal pathway. Notably, the combination of ALT and Wnt/ß-catenin inhibitor, as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation, migration and invasion of OS cells. Collectively, our results validate the ALT may inhibit proliferation, metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/ß-Catenin and MAPKs signaling pathways.

TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9.

Bone morphogenetic protein 9 (BMP9), also named as growth differentiation factor 2 (GDF-2), is the strongest cytokine that promotes osteogenic differentiation in the BMP family, and has broad clinical application value. Nevertheless, the mechanism of BMP9 promotes osteogenic differentiation remain unclear. TAZ, a transcriptional co-activator, has great effects on cell proliferation, differentiation, and stem cell self-renewal. In this research, we investigated the effects of TAZ in BMP9-induced osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 (MSCs) and murine multi-lineage cell lines C2C12 and MEFs (MMCs) and explored its possible mechanisms. This study has found that BMP9 induces the expression of TAZ and promotes its nuclear translocation. Meanwhile, our study found that Ad-TAZ and TM-25659, a TAZ agonist, can enhance the osteogenic differentiation of MSCs and MMCs induced by BMP9. Conversely, Ad-si-TAZ and verteporfin, an inhibitor of TAZ, have the contradictory effect. Likewise, the promotion of TAZ to the BMP9-induced ectopic bone formation in vivo was confirmed by the subcutaneous transplantation of MSCs in nude mice. Furthermore, we have detected that TAZ might increase the levels of the phosphorylation of Smad1/5/8, p38, ERK1/2, and JNK induced by BMP9. Additionally, we also found that TAZ increased the total protein level of ß-catenin induced by BMP9. In summary, our results strongly indicated that TAZ will promote the osteogenic differentiation in MSCs and MMCs induced by BMP9 through multiple signal pathways.

Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/ß-catenin, PI3K/AKT and NF-κB signaling pathways.

Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the activity of Wnt/ß-catenin, PI3K/AKT and NF-κB signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/ß-catenin, PI3K/AKT and NF-κB to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS.

Chordoma coexisting with Rathke's cleft cyst: case report and literature review.

Both chordoma and Rathke's cleft cyst are relatively rare diseases in the central nervous system. In this paper we report the first case of a chordoma coexisting with a Rathke's cleft cyst. A 49-year-old man presented with a 19-month history of distending pain, movement dysfunction and diplopia of the left eye. The preoperative diagnosis was consistent with chordoma with cystic change. Final pathological diagnosis of chordoma coexisting with Rathke's cleft cyst was made according to histological and immunohistochemical studies and the clinical and radiological features are discussed. Considering the close relationship between the notochordal tissue and Rathke's pouch during early embryogenic development, a possible mechanism is also discussed with the literature review.

Treatment of fresh leachate by microaeration pretreatment combined with IC-AO2 process: Performance and mechanistic insight.

Fresh leachate is commonly featured with high concentrations of degradable organic matters, which can impede the performance of traditional biological treatment, especially the anaerobic reactor. Aiming at improving the biological treatment process of fresh leachate, this study creatively proposed a microaerobic-IC-AO2 (MAICAO2) process and compared it with traditional biological process, then optimized the operating conditions. Meanwhile, this work investigated the transformation rules and molecular compositions of dissolved organic matters (DOM) during MAICAO2 process, particularly the hazardous DOM (antibiotics). The innovative MAICAO2 process can effectively remove 99% chemical oxygen demand (COD), 91% total nitrogen (TN) and 91% ammonia (NH4+-N) during the operation time, and the removal efficiencies of COD, TN and NH4+-N in MAICAO2 process increased approximately 2%, 14% and 13% compared to ICAOAO process. Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) confirmed that microaeration could ensure over 53% small molecular organic acids degrade before the subsequent anaerobic reaction so the system could resist the high concentration organic matters stress and improve the denitrification efficiency. Further analysis showed that different categories of antibiotics (including 6 sulfonamides, 4 tetracyclines, 2 macrolides, 4 quinolones and 2 chloramphenicols) could be effectively removed by MAICAO2 process with the total removal efficiency of 50%. This work proposed a new scenario for fresh leachate treatment by proposing the importance of the microaeration pretreatment during the biological treatment process.

Cardamonin inhibits the growth of human osteosarcoma cells through activating P38 and JNK signaling pathway.

Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C16H14O4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway.