Simulation on oily contamination removal by ozone using molecular dynamics.

Ozone (O3) is characteristic of high oxidative activity. It displays a high potential value in sterilization and decontamination. Although O3 has been widely investigated for its efficiency and environmentally friendly effectiveness, the fundamental issue regarding the complicated microscopic interaction mechanism between O3 and contaminant molecules remains largely unaddressed. We addressed this knowledge gap through molecular dynamics (MD) simulation at the molecular scale. Results indicated that five representative hydrocarbon molecules (n-hexadecane, phytane, terpane, naphthalin and acenaphthylene) on a rough silica (SiO2) surface were almost removed after about 300 ps simulation. And the aromatic molecules were easier to be removed than aliphatic ones. The hydroxyl oxidation reaction was demonstrated as a predominant mechanism. As the large dose of O3 was supplied by atmospheric air dielectric barrier discharge (DBD) plasma, this work provided an important theoretical reference for better using plasma technology for oily contaminant removal.

Photothermal MnO2 nanoparticles boost chemo-photothermal therapy-induced immunogenic cell death in tumor immunotherapy.

The induction of immunogenic cell death (ICD) is an attractive strategy for generating in situ autologous tumor cell-based vaccines and thus has great potential in cancer prevention and personalized immunotherapy. However, the effectiveness of ICD in tumor immunotherapy has been greatly limited, mainly by low induction efficiency and the immunosuppressive tumor microenvironment (TME). Herein, we report a new strategy for chemo-photothermal therapy-induced ICD by employing photothermal MnO2 nanoparticles loaded with doxorubicin (DOX) in tumor immunotherapy to overcome the low efficiency of traditional ICD inducers and the immunosuppressive TME. Specifically, we prepared photothermal bovine serum albumin (BSA)-templated MnO2 NPs (BSA/MnO2 NPs) with good aqueous dispersibility and high biocompatibility through the direct reduction of KMnO4 with BSA, and we then efficiently loaded DOX, an ICD inducer, onto the MnO2 NPs through coordination (DOX-BSA/MnO2 NPs). The DOX-BSA/MnO2 NPs achieved high photothermal conversion efficiency, highly efficient tumor targeting, TME-responsive DOX release and modulation of the hypoxic TME. Notably, a marked in vivo synergistic therapeutic effect was achieved in a triple-negative breast carcinoma-bearing mouse model by combining chemo-photothermal therapy-induced ICD with amelioration of the immunosuppressive TME. Our research highlights the great promise of modulating the TME with photothermal MnO2 nanosystems to enhance ICD-induced antitumor immunotherapy.

Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation.

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.

Qiliqiangxin Attenuates Adverse Cardiac Remodeling after Myocardial Infarction in Ovariectomized Mice via Activation of PPARγ.

BACKGROUND/AIMS: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. METHODS: Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Masson's Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and α-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting. RESULTS: These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor γ (PPARγ) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPARγ activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPARγ. CONCLUSION: The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPARγ, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.

Traditional Chinese Medication Qiliqiangxin Protects Against Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats.

Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Masson's trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-ß expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.

FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain.