Protein-based nanomedicine plays an important role in tumor chemotherapy due to their merits in bioavailability, biocompatibility, biodegradability, and low toxicity. In this study, we developed a novel method of preparing human serum albumin (HSA) nanoparticles for targeted delivery of paclitaxel (PTX) to tumors. HSA-PTX nanoparticles (NPs-PTX) were fabricated via unfolding of HSA in appropriate solution to expose more hydrophobic domains and consequent self-assembling into nanoparticles with added PTX. Via this self-assembly method, a desirable particle size (around 120 nm), a high drug loading (>20%), and a high encapsulation efficiency (near 100%) were obtained. PTX dispersed as an amorphous state in NPs-PTX and the secondary structures of HSA were maintained. In a cytotoxicity study, NPs-PTX displayed an enhanced cytotoxicity in MCF-7 and A549 cells. Confocal microscopy and flow cytometry revealed that the uptake of NPs-PTX was mediated by secreted protein acidic and rich in cysteine and "caveolar" transport. In H22 tumor-bearing mice, NPs-PTX displayed an increasing and everlasting tumor distribution, leading to slower tumor growth and longer mice survival than PTX. Therefore, this novel self-assembly method offers a much easier method to prepare PTX nanoparticles, provides better antitumor efficacy in vitro and in vivo, and more importantly, sets up a delivery platform for other hydrophobic drugs to improve their effectiveness in cancer therapy.

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Purpose: To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods:The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed.Results: Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA.Conclusion: HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis. Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation Wang DX et al. Acta Cir Bras. 2020;35(1):e202000105 2 Experimental grouping Eighty rats were randomly divided into the following 4 groups (n=20 in each group): (1) The sham group -the Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation Wang DX et al. Acta Cir Bras. 2020;35(1):e202000105 Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation Wang DX et al. Acta Cir Bras. 2020;35(1):e202000105 7

Background: Diabetic nephropathy (DN), as a complication of diabetes, is a leading cause of mortality in diabetic patients. It has been reported that lncRNA PVT1 (PVT1) could accelerate the progression of DN by promoting ECM accumulation and increasing the expression of fibronectin 1 (FN1). However, the underlying mechanism of PVT1 on DN remains unknown. Methods: To study the effect of PVT1 on DN, mice were injected 50 mg/kg STZ to build the DN models. Mesangial cells (MCs) were induced by high glucose as in vitro model of DN. The expression level of PVT1, miR-325-3 and Snail1 was assessed by qRT-PCR and Western blot. Luciferase reporter assay, RNA pull-down and RIP were used to explore the interaction among PVT1, miR-325-3 and Snail1. Results: In in vivo and in vitro DN models, the expression of PVT1 was upregulated. High glucose (HG) induced cell viability, oxidative stress, fibrosis and inflammation in MCs, which were reversed in the PVT1-KD MCs. The level of miR-325-3p was also increased in in vivo and in vitro experiments. Additionally, PVT1 can directly bind to miR-325-3p. Finally, Snail1 was a direct target of miR-325-3p. Conclusion: PVT1 inhibits viability, oxidative stress, fibrosis, and inflammation in DN via miR-325-3p/Snail1 axis.