The aim of this study was to compare the treatment response, survival, liver function, and adverse event incidence of drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres with conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Seventy-three patients with hepatocellular carcinoma who received drug-eluting bead transcatheter arterial chemoembolization (using CalliSpheres microspheres) or conventional transcatheter arterial chemoembolization treatment were consecutively enrolled. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors at month 1/month 3/month 6; posttreatment, liver function indexes, and adverse events were recorded. Progression-free survival and overall survival were also calculated. Objective response rate of patients at months 1, 3, and 6, disease control rate of patients and objective response rate of nodules at month 3 were increased in drug-eluting bead transcatheter arterial chemoembolization group compared with conventional transcatheter arterial chemoembolization group. In addition, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was an independent factor for predicting better objective response rate at month 1. Patients in drug-eluting bead transcatheter arterial chemoembolization group achieved longer progression-free survival and similar overall survival compared to those in conventional transcatheter arterial chemoembolization group; Cox proportional hazards regression model analyses revealed that drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was associated with better progression-free survival while it did not affect overall survival. Meanwhile, most of the occurrences of abnormal liver function indexes were similar between 2 groups, whereas drug-eluting bead transcatheter arterial chemoembolization group had a higher percentage of patients with total bile acid ≥2 upper limit of normal compared to conventional transcatheter arterial chemoembolization group at month 1. Moreover, the adverse event incidences between 2 groups were similar. In conclusion, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres achieves better treatment response and progression-free survival while equal safety compared to conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.
Verbascoside is a kind of phenylpropanoid glycoside derived from multiple medicinal plants, exerting anti-tumor effects in diverse human malignancies. However, the function of Verbascoside on the radiosensitivity of hepatocellular carcinoma (HCC) cells remains unknown. Human Huh7 and HepG2 cell lines were treated with Verbascosideis, and cell viability was detected with cell counting kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect miR-101-3p expression, and Western blot was used to quantify the expression of WEE1 G2 checkpoint kinase (WEE1). Then, CCK-8 and flow cytometry assays were used to detect the proliferation and apoptosis of HCC cells after Verbascoside and X-ray combined treatment, and the expressions of WEE1 and apoptosis-related proteins Bax and Bcl-2 were detected by Western blot. Verbascoside could improve the radiosensitivity of HCC cells in a dosedependent manner. Verbascoside increased the expression of miR-101-3p but reduced WEE1 expression in HCC cells. Additionally, WEE1 was identified as a target of miR-101-3p. MiR-101-3p inhibition or WEE1 overexpression could reverse the effect of Verbascoside on the viability and apoptosis of HCC cells. Verbascoside increases the radiosensitivity of hepatocellular carcinoma cells via modulating miR-101-3p/WEE1 axis.
Three new ester glycosides, named as Caesateroside A (1), Caesateroside B (2) and Caesateroside C (3) were obtained from the seeds of Caesalpinia sappan. The new structures of compounds 1-3 were elucidated by analyzing their 1D NMR, 2D NMR and HR-ESI-MS spectra. Compounds 1-3 showed weak-moderate cytotoxicity against Hela and HepG-2 human cancer cell lines.
Ionizing radiation (IR) brings many health problems to humans, causing damage to the digestive system, hematopoietic system, and immune system. Natural compounds derived from plants have attracted widespread attention due to their low toxicity. Here, we found that 3,4,5‐O‐tricaffeoylquinic acid (tCQA) extracted from natural plant Azolla imbricata could significantly alleviate the systemic damage in mice caused by IR. In order to further explore the molecular mechanism of the radioprotective effect of tCQA, in vitro experiments confirmed that tCQA could attenuate the cytotoxic effect of IR on the colonic epithelial cell line NCM460 and alleviate the IR‐induced mitochondrial dysfunction characterized by the decrease of mitochondrial transmembrane potential, ROS production, and caspase‐dependent apoptosis. In addition, the generation of ROS induced by H2O2 could also be reversed by tCQA. Then, Western blot demonstrated that tCQA could reverse the MAPK signaling pathway activated by IR. However, the inhibitory effect of tCQA on JNK and P38 levels activated by the JNK agonist anisomycin is not obvious; meanwhile, tCQA could inhibit the activation of JNK/P38 induced by H2O2, which suggests that tCQA might inhibit the JNK/P38 signaling pathway by reducing ROS. In short, tCQA inhibits the generation of ROS caused by IR, and then regulates the activity of caspase in the mitochondrial pathway by inhibiting the JNK/P38 signaling pathway, thereby alleviating the apoptosis of NCM460. This research provides an experimental basis for the development of new types of radioprotective agents for medical diagnosis and radiotherapy.
Deep eutectic solvents (DESs) are regarded as promising solvents to extract chemicals from plant materials. In this study, a DES-based microwave-assisted extraction (MAE) method was developed for the chromatographic analysis of four bioactive flavonoids in Spirodela polyrrhiza. Chromatographic separation was achieved on a Promosil C18-column. Prior to the HPLC analysis, the flavonoids were rapidly extracted by a DES–MAE process using choline chloride/levulinic acid (1:2, mol/mol) as the solvent. The extraction parameters were optimized using response surface methodology, and the optimal DES–MAE was fast and efficient compared with conventional solvent-based MAE and ultrasonic-assisted extraction using DES. The recoveries of optimized DES–MAE for the four flavonoids ranged from 97.80 to 103.29%. This study demonstrates that the validated DES–MAE–HPLC method is efficient, accurate and applicable to the determination of flavonoids in S. polyrrhiza.
To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. Patients with hematological diseases and neutropenia were included in the PPK model study.Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage. The follow-up dose adjustments were made according to the concentration results. This two-compartment model showed good stability and accuracy. The first trough concentration (C 0 ) and the compliance rate of the first C 0 were much higher in the model group than that in the non-model group (14.30 � 4.73 μg/ml and 59.38% vs. 8.02 � 2.61 μg/ml, 35.71%). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group (12.50% and 0.13 � 0.34 times vs. 50.00% and 0.61 � 0.66 times). This suggested that for those patients who had a Creatinine clearance rate (CLCR) ≥ 90 ml/min/1.73 m 2 , the initial dose of 1g q8h may help to reach the target C 0 (10∼20 μg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration and reduce the number of dose adjustments.Clinical trial registration: Not applicable (Retrospective study).
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