Simvastatin (SV) is a statin drug that can effectively control cholesterol and prevent cardiovascular diseases. However, SV is water-insoluble, and poor oral bioavailability (<5 %). Solid self-emulsifying carrier system is more stable than liquid emulsions, facilitating to improve the solubility and bioavailability of poorly soluble drugs. In the present study, a solid self-emulsifying carrier stabilized by casein (Cas-SSE) was successfully used to load SV to improve its solubility in water, by formulation selection and emulsification process optimization. Compared with oral tablets, the release of SV from Cas-SSE was significantly enhanced in artificial intestinal fluid. Furthermore, everted gut sac experiments indicated some water-soluble dispersing agents such as hydroxyethyl starch (HES), were not conducive to drug absorption. Pharmacokinetic studies suggested Cas-SSE without dispersing agent has much higher relative bioavailability (184.1 % of SV and 284.5 % of simvastatin acid) than SV tablet. The present work suggests Cas-SSE is a promising drug delivery platform with good biocompatibility for improving oral bioavailability of poorly water-soluble drugs.

The embolic agent based on PNIPAM thermosensitive nanogels exhibited excellent biocompatibility and demonstrated long-term, precise embolization ability.

Growth hormone (GH) exhibited the important biological activities in the mesenchymal stem cell (MSCs). However, the cellular behavior and properties of GH/GHR in MSCs remain unclear. A series of experiments (such as confocal laser scanning microscope [CLSM] and Western-blot) were performed to systematically investigate the cellular behavior of GH/GHR in MSCs, and the results showed that GH/GHR not only internalized into the cytoplasm, but also transported into the cell nuclei of MSCs. Furthermore, we studied the molecular mechanism by which GH/GHR internalized into cell, and the results indicated that clathrin plays more important role in the process of GHR internalization. More importantly, it can be found that nuclear-targeted GHR has the important biological functions in MSCs, which could promote MSCs proliferation. We further revealed the molecular mechanism by which nuclear-localized GHR regulates MSCs proliferation, and found that nuclear-targeted GHR enhanced the phosphorylation of STAT5, and the activated STAT5 initiates the transcription of CyclinD1, after which, the complex of CyclinD1 and CDK4 further phosphorylates Rb, and the activated Rb releases E2F1, the released E2F1 ultimately realizes the biological function of GH promoting cell proliferation. In short, in the current study，we used MSCs as a model to study the cellular behavior and properties of GH/GHR, and found that GH/GHR can internalize into cell cytoplasm and transport into the cell nuclei. Further work showed that nuclear GHR could drive cell proliferation via GHR/STAT5/CyclinD1 signaling pathway. The current research has laid an important foundation for further study on the regulatory effect of GH on MSCs.

T-cell lymphomas are a heterogeneous group of cancers with different pathogenesis and poor prognosis.Histone deacetylases (HDACs) are epigenetic modifiers that modulate many key biological processes.In recent years, HDACs have been fully investigated for their roles and potential as drug targets in T-cell lymphomas.In this review, we have deciphered the modes of action of HDACs, HDAC inhibitors as single agents, and HDACs guided combination therapies in T-cell lymphomas.The overview of HDACs on the stage of T-cell lymphomas, and HDACs guided therapies both as single agents and combination regimens endow great opportunities for the cure of T-cell lymphomas.

Placenta-specific 1 (PLAC1), a novel cancer-testis antigen (CTA), is expressed in a number of different human malignancies. It is frequently produced in breast cancer, serving a function in tumorigenesis. Adoptive immunotherapy using T cell receptor (TCR)-engineered T cells against CTA mediates objective tumor regression; however, to the best of our knowledge, targeting PLAC1 using engineered T cells has not yet been attempted. In the present study, the cDNAs encoding TCRα- and β-chains specific for human leukocyte antigen (HLA)-A*0201-restricted PLAC1 were cloned from a cytotoxic T-lymphocyte, generated by in vitro by the stimulation of CD8+ T cells using autologous HLA-A2+ dendritic cells loaded with a PLAC1-specific peptide (p28-36, VLCSIDWFM). The TCRα/β-chains were linked by a 2A peptide linker (TCRα-Thosea asigna virus-TCRβ), and the constructs were cloned into the lentiviral vector, followed by transduction into human cytotoxic (CD8+) T cells. The efficiency of transduction was up to 25.16%, as detected by PLAC1 multimers. TCR-transduced CD8+ T cells, co-cultured with human non-metastatic breast cancer MCF-7 cells (PLAC1+, HLA-A2+) and triple-negative breast cancer MDAMB-231 cells (PLAC1+, HLA-A2+), produced interferon γ and tumor necrosis factor α, suggesting TCR activation. Furthermore, the PLAC1 TCR-transduced CD8+ T cells efficiently and specifically identified and annihilated the HLA-A2+/PLAC1+ breast cancer cell lines in a lactate dehydrogenase activity assay. Western blot analysis demonstrated that TCR transduction stimulated the production of mitogen-activated protein kinase signaling molecules, extracellular signal-regulated kinases 1/2 and nuclear factor-κB, through phosphoinositide 3-kinase γ-mediated phosphorylation of protein kinase B in CD8+ T cells. Xenograft mouse assays revealed that PLAC1 TCR-transduced CD8+T cells significantly delayed the tumor progression in mice-bearing breast cancer compared with normal saline or negative control-transduced groups. In conclusion, a novel HLA-A2-restricted and PLAC1-specific TCR was identified. The present study demonstrated PLAC1 to be a potential target for breast cancer treatment; and the usage of PLAC1-specific TCR-engineered T cells may be a novel strategy for PLAC1-positive breast cancer treatment.

Aims: To analyze the changes of CD4+T-cell subsets following radiofrequency ablation (RFA) in lung cancer and the impact of RFA on the antitumor immunity. Subjects and Methods: Flow cytometry was employed to detect CD4+T-cell subsets in the peripheral blood from 45 healthy controls and 45 lung cancer patients before and after RFA. The correlation between CD4 +T-cell subsets and the clinical characteristics was discussed by comparing the results between different groups. Results: Compared with the healthy controls, the lung cancer patients showed a decline in Th1 cells, but higher Th2, Th17, and Treg cells (P < 0.05). Th1 cell level and Th1/Th2 cell ratio were significantly lower for stage III/IV than Stage I/II and also lower for patients with Karnofsky Performance Status (KPS) score <60 than ≥ 60 (P < 0.05). The levels of Th2, Th17, and Treg cells were much higher for patients with Stage III/IV and KPS score <60 (P < 0.05). After 2 weeks of RFA, the level of Th1 cells and Th1/Th2 cell ratio increased, while the levels of Th2, Th17, and Treg cells declined (P < 0.05). For lesions with ablation volume ≥ 70%, the level of Th1 cells and Th1/Th2 cell ratio increased, whereas the levels of Th2, Th17, and Treg cells declined dramatically (P < 0.05). Conclusions: The level of Th1 cells declined in lung cancer patients, especially for patients with Stage III/IV and KPS score <60. After RFA, the level of Th1 cells and Th1/Th2 increased, whereas the levels of Th2, Th17, and Treg cells declined, indicating an improvement of antitumor immunity. The changes were more prominent for lesions with ablation volume ≥ 70%.