Self-supplying Cu2+ and H2O2 synergistically enhancing disulfiram-mediated melanoma chemotherapy.

Disulfiram (DSF) can target and kill cancer cells by disrupting cellular degradation of extruded proteins and has therefore received particular attention for its tumor chemotherapeutic potential. However, the uncontrollable Cu2+/DSF ratio reduces the efficacy of DSF-mediated chemotherapy. Herein, self-supplying Cu2+ and oxidative stress synergistically enhanced DSF-mediated chemotherapy is proposed for melanoma-based on PVP-coated CuO2 nanodots (CPNDs). Once ingested, DSF is broken down to diethyldithiocarbamate (DTC), which is delivered into a tumor via the circulation. Under the acidic tumor microenvironment, CPNDs produce sufficient Cu2+ and H2O2. DTC readily chelates Cu2+ ions to generate CuET, which shows antitumor efficacy. CuET-mediated chemotherapy can be enhanced by H2O2. Sufficient Cu2+ generation can guarantee the maximum efficacy of DSF-mediated chemotherapy. Furthermore, released Cu2+ can be reduced to Cu+ by glutathione (GSH) and O2- in tumor cells, and Cu+ can react with H2O2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, promoting the efficacy of CuET. Therefore, this study hypothesizes that employing CPNDs instead of Cu2+ ions could enhance DSF-mediated melanoma chemotherapy, providing a simple but efficient strategy for achieving chemotherapeutic efficacy.

Diagnostic Performance of US and MRI in Predicting Malignancy of Soft Tissue Masses: Using a Scoring System.

Objective: To assess the diagnostic performance of US and MRI in predicting malignancy of soft tissue masses by using a scoring system. Methods: A total of 120 cases of pathologically confirmed soft tissue masses (71 cases of malignant lesions and 49 cases of benign lesions) were enrolled. All patients underwent ultrasound and MRI examination prior to biopsy or surgical excision. A scoring system based on the parameters of conventional US and MRI to distinguish malignant and benign masses was established by the regression model. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of US and MRI. Results: Multivariate analysis showed that margin, maximum diameter, and vascular density were independent predictors for malignancy found by US, while maximum diameter, margin, and affected peripheral soft tissue were independent predictors for malignancy found by MRI. The mean scores of the benign and malignant groups were 2.8 ± 1.6, 5.1 ± 1.1 on US and 1.3 ± 1.2, 3.5 ± 0.9 on MRI. Based on the cut-off score of 3.5 and 2.5 calculated by ROC analysis, US and MRI had 92% and 87% sensitivity, 72% and 76% specificity, 86% and 89% accuracy, respectively. The combination of these two modalities achieved the sensitivity of 91%, specificity of 82%, and accuracy of 93%. Conclusions: Both US and MRI can provide valuable information about the differential diagnosis between benign and malignant soft tissue masses. The combination of the two imaging-based scoring systems can increase the diagnostic performance, especially in specificity.

Diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules.

Fine needle aspiration biopsy is a crucial method for preoperative diagnosis of thyroid nodules. However, thyroid nodules classified as Bethesda categories III-V cannot obtain definite cytological results. Our aim was to study the diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules, so as to provide more precise direction for the follow-up treatments. A total of 174 Bethesda categories III-V thyroid nodules performed TIRADS and BRAFV600E mutation analysis were included in the study. We retrospectively analyzed the ultrasound features as well as the results of BRAFV600E mutation of the 174 thyroid nodules. In the multiple regression analysis models, ultrasound features including lobulated or irregular margin, punctate echogenic foci, and shape with taller-than-wide were statistically significant in malignant nodules (p < 0.05). The area under the curve of the combination of TIRADS and BRAFV600E increased to 0.925, which were much higher than TIRADS (0.861) and BRAFV600E (0.804) separately. Combined diagnosis was of the greatest value to identify Bethesda III-V thyroid nodules definitely, especially with higher sensitivity (93%) and accuracy (90%).

Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling.

Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK-8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual-energy X-ray absorptiometry (DEXA) and micro-CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling.

808 nm Near-Infrared Light-Excited UCNPs@mSiO2-Ce6-GPC3 Nanocomposites For Photodynamic Therapy In Liver Cancer.

BACKGROUND: It is important to explore effective treatment for liver cancer. Photodynamic therapy (PDT) is a novel technique to treat liver cancer, but its clinical application is obstructed by limited depth of visible light penetration into tissue. The near-infrared (NIR) photosensitizer is a potential solution to the limitations of PDT for deep tumor tissue treatment. PURPOSE: We aimed to investigate 808 nm NIR light-excited UCNPs@mSiO2-Ce6-GPC3 nanocomposites for PDT in liver cancer. METHODS: In our study, 808 nm NIR light-excited upconversion nanoparticles (UCNPs) were simultaneously loaded with the photosensitizer chlorin e6 (Ce6) and the antibody glypican-3 (GPC3), which is overexpressed in hepatocellular carcinoma cells. The multitasking UCNPs@mSiO2-Ce6-GPC3 nanoparticles under 808 nm laser irradiation with enhanced depth of penetration would enable the effective targeting of PDT. RESULTS: We found that the UCNPs@mSiO2-Ce6-GPC3 nanoparticles had good biocompatibility, low toxicity, excellent cell imaging in HepG2 cancer cells and high anti-tumor effect in vitro and in vivo. CONCLUSION: We believe that the utilization of 808 nm NIR excited UCNPs@mSiO2-Ce6-GPC3 nanoparticles for PDT is a safe and potential therapeutic option for liver cancer.