Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes / 中国结合医学杂志

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Preparation of Lappaconitine-Loaded Microemulsion with Olive Oil and Research on Its Properties / 中国药学杂志

OBJECTIVE: To prepare lappaconitine(LA)-loaded microemulsion with olive oil and study its morphology, particle size, drug loading capacity, drug release behavior and rheological characteristics. METHODS: Pseudo-ternary phase diagram method was used to screen and prepare LA-loaded microemulsion with olive oil. LA release properties in vitro were investigated by dynamic dialysis method. The rheological properties of LA-loaded microemulsion with olive oil were studied using MCR 301 rheometer. RESULTS: The optimal formulation of LA-loaded microemulsion with olive oil was as follows:olive oil was the oil phase, castor oil polyoxyethylene ether-40/span-80(4:1) was the surfactant, glycerin was the cosurfactant, and Km=3. The morphology of the microemulsion particles was round or oval, and the average particle size was(91±0.55) nm. The drug-loading rate of LA in the microemulsion was 1.85%.Drug release experiments in vitro showed that the microemulsion had a sustained release effect on LA, and the drug release behavior was more suitable to be described by Higuchi equation. Rheological experiments showed that the fluid of LA-loaded microemulsion with olive oil belong to pseudoplastic fluid of non-Newtonian fluid exhibiting thixotropic and shear-thinning fluid behavior as well as certain viscoelasticity. CONCLUSION: The LA-loaded microemulsion witholive oil are successfully prepared, and the microemulsion has ideal sustained release behavior and good rheological properties. The study provides a foundation for the developmenton preparation of LA-loaded microemulsion with olive oil.

Construction and expression of an anti-EGFR/anti-KDR bispecific single-chain diabody / 药学学报

Bispecific antibodies have been exploited as both cancer immunodiagnostics and cancer therapeutics, which have shown promises in clinical trials in cancer imaging and therapy. To improve the anti-tumor effect, an scDb (bispecific single-chain diabody) was constructed from the variable domain genes of two scFvs (single-chain variable fragment antibodies) directed against human EGFR (epidermal growth factor receptor) and VEGFR2 (vascular endothelial growth factor receptor 2) extracellular domains. The anti-EGFR/ anti-KDR scDb was constructed into pHEN2 plasmid and expressed in Escherichia coli HB2151 host. After purification by one-step affinity chromatography of IMAC, scDb protein was characterized by Western blotting. The yield of scDb protein was 570 microg per liter medium. scDb bound to EGFR as efficiently as the parental antibody scFv-E10, while a little bit weaker than the parental antibody scFv-AK404R when bound to KDR. In conclusion, the scDb protein could bind both EGFR and KDR specifically and could be applied for further anti-tumor research.