Recent Advances of D-α-tocopherol Polyethylene Glycol 1000 Succinate Based Stimuli-responsive Nanomedicine for Cancer Treatment.

D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA. It's widely applied as a multifunctional drug carrier for nanomedicine. The advantages of TPGS include P-glycoprotein (P-gp) inhibition, penetration promotion, apoptosis induction via mitochondrial-associated apoptotic pathways, multidrug resistant (MDR) reversion, metastasis inhibition and so on. TPGS-based drug delivery systems which are responding to external stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect, through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior. In this review, TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed, including pH-responsive, redoxresponsive and multi-responsive systems in various formulations. The achievements, mechanisms and different characteristics of TPGS-based stimuli-responsive drug-delivery systems in tumor therapy were also outlined.

Immunoregulatory Effects of Subcutaneous Immunotherapy on Lymphocyte Subgroups and Cytokines in Children with Asthma.

OBJECTIVE: Asthma is a syndrome that incorporates many immune phenotypes. The immunologic effects of subcutaneous immunotherapy (SCIT) exerts on allergic asthma remain still largely unknown. Here, we investigated the effects of SCIT on cytokine production and peripheral blood levels of lymphocyte subtypes in children with mite-induced moderate and severe allergic asthma. METHODS: The study included 60 kids with mite-induced allergic asthma from 5 to 10 years old. All subjects had received antiasthmatic pharmacologic for 3 months at baseline. Half of the children were treated with SCIT combined with pharmacologic treatment named the SCIT group and the other half only with pharmacologic therapy named the no-SCIT group. Total asthma symptom score (TASS) and total medication score (TMS) were recorded. Flow cytometry was used to identify lymphocyte subtypes: type 2 innate lymphocytes (ILC2s), type 1 (Th1) and type 2 (Th2) helper T cells, T helper 17 (Th17) cells, and regulatory T (Treg) cells. ELISA, flow cytometry, and cytometric bead array were used to assess cytokines IL-13, IFN-γ, IL-4, IL-17, and TGF-ß, at baseline and 3 and 6 months after study treatment in both groups of patients. RESULTS: Both groups can significantly improve clinical symptoms in children with asthma. SCIT can significantly reduce asthma medication after 6 months of treatment. SCIT induced a significantly higher and progressive reduction in ILC2 percentage and IL-13 levels after 3 and 6 months of treatment compared with baseline and compared with no-SCIT patients. Significant differences were detected in the Th1/Th2 cell ratio and IFN-γ/IL-4 cytokine ratio between groups after 6 months of treatment. Similarly, the Th17/Treg ratio and IL-17/TGF-ß ratio in the SCIT group were much lower than those in the no-SCIT group after 3-6 months of treatment. CONCLUSION: SCIT is a promising option to reduce the percentage of ILC2 and regulate Th1/Th2 and Th17/Treg immune balance in the peripheral blood of children with asthma.

Sputum metabolomic profiling of bronchial asthma based on quadruple time-of-flight mass spectrometry.

To improve diagnosis of asthma, we tend to confirm potential biomarkers by comparing sputum metabolome profiles between asthma patients and healthy controls, using ultra-high-performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Thirty endogenous metabolites contributing to the separation of asthma patients and healthy controls were tentatively identified in positive mode, such as 1-hexadecanoyl-sn-glycerol, glycerol 1-stearate, sphingosine, Phe-Ser, Tyr-Ala and Phe-Gln, and 12 endogenous metabolites were identified in negative mode, such as cytidine 2',3'-cyclic phosphate, 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-rac-glycerol), 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoserine, thymidine, gamma-L-glutamyl-L-valine and adenine. Those differential metabolites were mainly participatedin glycerophospholipid metabolism, retrograde endocannabinoid signaling and metabolic pathways in positive mode and 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine degradation and metabolic pathways in negative mode. Importantly, several metabolic pathways including glycerophospholipid metabolism, inositol phosphate metabolism, and glycolysis or gluconeogenesis were found most important. These findings suggest sputum metabolomics can be used for the early diagnosis and risk prediction of asthma.