Magnesium lithospermate B inhibits titanium particles-induced osteoclast formation by c-fos and inhibiting NFATc1 expression.

Purpose: Titanium particle-induced osteolysis is one of the important causes of aseptic loosening of artificial joints. Previous studies have shown the potential of natural compounds in preventing Ti particle-induced bone resorption. In this study, we observed the effects of magnesium lithospermate B (MLB) on titanium particle-induced osteoclast activity in vitro. Materials and Methods: RAW264.7 cells were treated with titanium particles (0.1 mg/mL) in the presence or absence of MLB (200 nmol/L). We evaluated the osteoclast formation, bone pits formation and tartrate-resistant acid phosphatase 5b (Tracp5b) levels. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to evaluate osteoclast differentiation-related genes (TRAF6, NFATc1, and c-fos) and protein expression. Results: The number of osteoclasts, pit formation and Tracp5b levels were all the group treated with titanium particles compared to the control group (all p < 0.05). Titanium particles also promoted the expression of the TRAF6, NFATc1 and c-fos genes and protein expression. MLB significantly abolished the titanium particle-enhanced osteoclast and pits formation, and Traf6, NFATc1, and c-fos expression. Conclusions: Our data demonstrated that MLB can suppress titanium-induced osteoclast activity via inhibiting c-fos and NFATc1 expression.

Co-amorphous formulation of dipyridamole with p-hydroxybenzoic acid: Underlying molecular mechanisms, physical stability, dissolution behavior and pharmacokinetic study.

Coamorphization has been proven to be an effective approach to improve bioavailability of poorly soluble active pharmaceutical ingredients (APIs) by virtue of solubilization, and also contributes to overcome limitation of physical stability associated with amorphous drug alone. In current work, a co-amorphous formulation of dipyridamole (DPM), a poor solubility drug, with p-hydroxybenzoic acid (HBA) was prepared and investigated. At a molar ratio of 1:2, DPM and HBA were melted result in the formation of a binary co-amorphous system. The DPM-HBA co-amorphous was structurally characterized by powder X-ray diffraction (PXRD), temperature modulated differential scanning calorimetry (mDSC), high performance liquid chromatography (HPLC) and solution state 1H nuclear magnetic resonance (1H NMR). The molecular mechanisms in the co-amorphous were further analysed via Fourier-transform infrared (FTIR) and Raman spectroscopies, as well as density functional theory (DFT) calculation. All the results consistently revealed the presence of hydrogen bonding interactions between -OH of DPM and -COOH on HBA. Accelerated test and glass transition kinetics showed excellent physical stability of DPM-HBA co-amorphous compared with amorphous DPM along with glass transition temperatures (Tg). The phase-solubility study indicated that complexation occurred between DPM and HBA in solution, which contributed to the solubility and dissolution enhancement of DPM in co-amorphous system. Pharmacokinetic study of co-amorphous DPM-HBA in mouse plasma revealed that the DPM exhibited 1.78-fold and 2.64-fold improvement in AUC0­∞ value compared with crystalline and amorphous DPM, respectively. This current study revealed coamorphization is an effective approach for DPM to improve the solubility and biopharmaceutical performance.

Combined treatment with anlotinib and chemotherapy for advanced esophageal squamous cell carcinoma improved patient survival: a case report.

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in Eastern Asia. Historically, advanced ESCC treatments have had low efficacy and new treatments, including immunotherapy or combination therapies, are emerging. Here, we report a special case of recurrent ESCC after surgery. The patient had a failed immunotherapy course, but benefited from anlotinib combined with chemotherapy for a fourth-line therapy. Survival after the combined therapy was greater than 19 months, and the overall patient survival was greater than 32 months.