No abstract

No abstract

In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.

Background This article is a meta-analysis aiming to systematically assess the efficacy and safety profiles of PD-1/PD-L1 inhibitors in patients with advanced or metastatic bladder cancer. Methods We extracted and examined data from phase I, II, and III clinical trials from the Medline, Embase, and the Cochrane Library, which included patients with metastatic bladder cancer who were treated with PD-1/PD-L1 inhibitors. We performed a meta-analysis to investigate several indexes of efficacy and safety, including the objective response rate (ORR), 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, and adverse event (AE) rate of immune checkpoint inhibitors. The material data were calculated and pooled using The R Project for Statistical Computing and Review Manager 5.3. Results After excluding ineligible records, 14 clinical trials were included in our analysis. The pooled frequencies of all-grade AEs and grade ≥3 AEs were 0.63 (95% CI 0.61–0.65, P =0.34) and 0.14 (95% CI 0.11–0.17, P =0.0072), respectively. The summary ORR was 0.21 (95% CI 0.18–0.24 P =0.07), and the 1-year OS and 1-year PFS rates were 0.48 (95% CI 0.42–0.54 P =0.0013) and 0.21 (95% CI 0.16–0.26 P =0.04), respectively. The OR of ORR between the PD-L1-positive and -negative groups was 3.09 (95% CI 2.01–4.75, P =0.08). Conclusion The PD-1/PD-L1 therapy showed appropriate efficacy and acceptable incidence of treatment-related AEs. In addition, the level of discrimination of PD-L1 expression might be related to the effect of the PD-1/PD-L1 inhibitors, and patients displaying positive expression might experience a better curative effect than patients displaying negative expression.

Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in HO-induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of HO to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in HO-induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated HO-induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in HO-induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated HO-induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated HO-induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.