Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.

SCOPE: Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. METHODS AND RESULTS: This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. CONCLUSION: This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.

Construction and evaluation of a phospholipid-based phase transition in situ gel system for brexpiprazole.

The objective of this study was to develop phospholipid-based injectable phase transition in situ gels (PTIGs) for the sustained release of Brexpiprazole (Brex). Phospholipid (Lipoid S100, S100) and stearic acid (SA) were used as the gel matrix which was dissolved in biocompatible solvent medium-chain triglyceride (MCT), N-methyl pyrrolidone (NMP), and ethanol to obtain PTIGs solution. The Brex PTIG showed a solution condition of low viscosity in vitro and was gelatinized in situ in vivo after subcutaneous injection. Both in vitro release assay and in vivo pharmacokinetics study in SD rats displayed that Brex in PTIGs could achieve a sustained release, compared with brexpiprazole solution (Brex-Sol) or brexpiprazole suspension (Brex-Sus). The Brex-PTIGs had good degradability and biocompatibility in vivo with rare inflammation at the injection site. Among the three Brex-PTIG formulations, Brex-PTIG-3 with the SA in the formulation had the greatest gelation viscosity, the lowest initial release rate, and the most stable release profile with sustained release of up to 60 days. The above results indicated that, as a novel drug delivery system, the Brex-PTIGs offered a new option for the clinical treatment of patients with schizophrenia.

MiR-190b impedes pancreatic ß cell proliferation and insulin secretion by targeting NKX6-1 and may associate to gestational diabetes mellitus.

BACKGROUND: The dysfunction of pancreatic ß cells is related to the occurrence of gestational diabetes mellitus (GDM). This study aimed to investigate the mechanism underlying the effects of miR-190b on pancreatic ß cell proliferation and insulin secretion. METHODS: Quantitative real-time PCR was used to detect miR-190b expression in placenta tissues from GDM patients. The effects of miR-190b on islet cells activity, proliferation, and insulin secretion were measured using MTT assay, BrdU staining, and ELISA. The relationship between miR-190b and NK6 homeobox 1 (NKX6-1) was ensured by dual luciferase reporter assay. RESULTS: MiR-190b was overexpressed in placenta tissues from GDM patients compared to normal pregnant woman. MiR-190b inhibitor inhibited the cell activity, proliferation, and insulin secretion of islet ß cells, while miR-190b overexpression had an opposite effect. Additionally, miR-190b negatively regulated NKX6-1 expression. Overexpression of NKX6-1 reversed the inhibitory effect of miR-190b-mimics on islet ß cell activity, proliferation, and insulin secretion. In mouse islets, knockdown of miR-190b promoted insulin secretion by up-regulating NKX6-1 expression. CONCLUSION: Silence of miR-190b accelerated pancreatic ß cell proliferation and insulin secretion via targeting NKX6-1, which might be a mechanism underlying the effects of miR-190b on the progression of GDM.

[Clinical study of Jiawei Bazhen decoction combined with oxytocin for cervical ripening of qi and blood deficiency type of pregnant women].

To study preliminarily the effect of Jiawei Bazhen decoction combined with oxytocin in promoting cervical ripening of full-term pregnancy women who were in the deficiency of qi and blood type through the syndrome differentiation of traditional Chinese medicine (TCM). 180 patients that met the inclusion criteria of the study were randomly divided into three groups: the control group(oxytocin group), the treatment group (Jiawei Bazhen decoction combined with oxytocin group), the blank control group (expected and observation group). Cervical maturity score (Bishop score), vaginal and cervical secretions fetal fibronectin (FFN), the result of induced labor, the result of mother and baby were observed in each group before and after treatment. The result comes out that the cervical Bishop score of pregnant women for treatment group were significantly higher than the control group and blank control group after treatment (P < 0.05). The FFN of pregnant women for the treatment group were significantly different from the control group and blank control group after treatment (P < 0.05). The pregnancy outcome of the three groups: the labor rate and rate of vaginal delivery of the treatment group were higher than the other two groups, and the difference was statistically significant (P < 0.05). The cesarean section rate of the treatment group was significantly lower than the other two groups, the difference was also statistically significant (P < 0.05). The three groups did not appear the phenomenon of neonatal asphyxia. Jiawei Bazhen decoction combined with oxytocin is effective in producing cervical ripening and induce labor. It is convenient, safe and reliable, for it is no obvious adverse effects on mother and fetus, but effective in reducing the rate of cesarean section, and playing a positive role in promoting natural delivery.

[Determination of germanium in aloe vera by spectrophotometric method].

OBJECTIVE: To analyze the organic germanium in aloe vera from different localities. METHODS: The method was based on germanium forms a stable complex with phenylfluorone in the acidified solution and CTMAB as solubilization agent. The contents of the organic germanium in Aloe vera from different localities were determined by spectrophotometric methods. RESULTS: The linear range of determination is 0-0.7 microg/ml. The recovery is 98.1%-99.0% and the coefficient of variation is 1.8%.