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Context: Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability. Objective: This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy. Materials and methods: Curcumin nanosuspensions (CUR-NSps) were prepared by precipitationultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer. Results: CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of À19.00 ± 1.31 mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CURNSps exhibited a significantly greater AUC 0-24 and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p50.01). Conclusions: These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer.

The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4 T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4 T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4 T cells from UC patients. Naive CD4 T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the promoter to enhance the expression of IL-4 in CD4 T cells. CD4 T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation.

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In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG 1000 -HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG 1000 -HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC 50 value against HepG2 cells and 14.1 times lower IC 50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG 1000 -HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy.

Recently, genkwanin (GKA) has been shown to display in vitro antitumor activity against some cancer cells, but its poor solubility restricted the in vivo study and further investigation of its antitumor therapeutic efficacy. In this paper, genkwanin nanosuspensions (GKA-NSps) were successfully prepared using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer using the precipitation-homogenization method. The obtained GKA-NSps had an average particle size of 183.1 ± 4.4 nm, a PDI value of 0.16 ± 0.07, a zeta potential of -16.2 ± 0.1 mV, and a drug loading content of 49.36 ± 0.14%. GKA-NSps showed spherical morphology and very good stability in normal saline, phosphate buffer saline (PBS, pH 7.4), 5% glucose, artificial gastric juice, artificial intestinal juice and plasma; thus, it is suitable for both oral and intravenous administration. The resultant GKA-NSps displayed sustained drug release behavior and stronger in vitro cytotoxicity against 4T1, MCF-7, MDA-MB-453, HeLa, HepG2, BT474, and A549 cells than free GKA. The in vivo study in MCF-7 tumor-bearing nude mice indicated that GKA-NSps (60 mg/kg, i.v.) achieved similar therapeutic efficacy as PTX injection (8 mg/kg, i.v.) (62.09% vs. 61.27%), while the minimal lethal dose was more than 320 mg/kg, indicating good safety. By using nanotechnology, our study suggested that some antitumor flavonoids of low potency, such as GKA, are promising as safe but effective anticancer drugs.

TNF can suppress the expression of IL-10 in B cells via enhancing the expression of HDAC11. Inhibition of HDAC11 restores the IL-10 expression in B cells of AR subjects. HDAC11 may be a novel target for the treatment of AR.

A simple and low-cost electrochemical sensor based on multimodified screen-printed electrodes (SPEs) was successfully synthesized for the sensitive detection of β-lactoglobulin (β-Lg). The surface treatment of SPEs was accomplished by a simple drip coating method using polyethyleneimine (PEI), reduced graphene oxide (rGO), and gold nanoclusters (AuNCs), and the treated SPEs showed excellent electrical conductivity. The modified SPEs were then characterized with UV-Vis, SEM, TEM, and FTIR to analyze the morphology and composition of the AuNCs and the rGO. An anti-β-Lg antibody was then immobilized on the composite material obtained by modifying rGO with PEI and AuNCs (PEI-rGO-AuNCs), leading to the remarkable reduction in conductivity of the SPEs due to the reaction between antigen and antibody. The sensor obtained using this novel approach enabled a limit of detection (LOD) of 0.08 ng/mL and a detection range from 0.01 to 100 ng/mL for β-Lg. Furthermore, pure milk samples from four milk brands were measured using electrochemical sensors, and the results were in excellent agreement with those from commercial enzyme-linked immunosorbent assay (ELISA) methods.