Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation.

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H-1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

Baseplate inferior offset affects shoulder range of motion in reverse shoulder arthroplasty in Asian population.

BACKGROUND: Impingement is a common complication of reverse shoulder arthroplasty. Placement of the baseplate with a wide impingement-free angle is ideal; however, there are few studies on Asian populations, which have smaller height and physique, and there is a lack of guidance on achieving optimal outcomes. The purpose of the present study was to explore the impingement-free range of motion reverse shoulder arthroplasty and analyze the suitable baseplate position or tilt for the Asian population using simulation software. METHODS: We uploaded computed tomography scan data from 20 Asian patients to three-dimensional (3D) simulation software. The implantation of the reverse shoulder arthroplasty component was performed on the 3D humerus and scapula using software, and range of motion was assessed until impingement occurred. RESULTS: The range of motion in flexion significantly improved when the baseplate was lowered up to 3 mm inferiorly. Range of motion in abduction and internal and external rotation significantly improved as the baseplate was lowered up to 4 mm. There was no significant difference in range of motion in any motion after changing the inferior tilt, except in internal and external rotation. CONCLUSIONS: The range of motion in abduction, flexion, and internal and external rotations significantly improved with increased inferior offset. These results may prove valuable in determining the optimal baseplate position for RSA, particularly in Asian populations.

Novel functional anti-HER3 monoclonal antibodies with potent anti-cancer effects on various human epithelial cancers.

Resistance of progressive cancers against chemotherapy is a serious clinical problem. In this context, human epidermal growth factor receptor 3 (HER3) can play important roles in drug resistance to HER1- and HER2- targeted therapies. Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Novel rat mAbs reacted with HEK293 cells expressing HER3, but not with cells expressing HER1, HER2 or HER4. Specificity of mAbs was substantiated by the loss of mAb binding with knockdown by siRNA and knockout of CRISPR/Cas9-based genome-editing. Analyses of CDR sequence and germline segment have revealed that seven mAbs are classified to four groups, and the binding of patritumab was inhibited by one of seven mAbs. Seven mAbs have shown reactivity with various human epithelial cancer cells, strong internalization activity of cell-surface HER3, and inhibition of NRG1 binding, NRG1-dependent HER3 phosphorylation and cell growth. Anti-HER3 mAbs were also reactive with in vivo tumor tissues and cancer tissue-originated spheroid. Ab4 inhibited in vivo tumor growth of human colon cancer cells in nude mice. Present mAbs may be superior to existing anti-HER3 mAbs and support existing anti-cancer therapeutic mAbs.

Intimal Sarcoma of the Pulmonary Artery Treated with Pazopanib.

Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.