Clinical study of Tongdu Shujin decoction in the treatment of ankylosing spondylitis with cold-dampness obstruction type: Study protocol for a randomized controlled trial.

BACKGROUND: Ankylosing spondylitis (AS) has a high incidence, and severe cases can lead to spinal deformity and even joint fusion, which causes a huge burden on patients life, work and psychology. Tongdu Shujin decoction (TDSJ) has a definite effect in the treatment of ankylosing spondylitis, so we designed a randomized controlled trial to observe the efficacy of TDSJ in the treatment of AS, and to evaluate its safety. METHODS: In this randomized controlled trial, 80 eligible patients were randomly assigned in a 1:1 ratio to a treatment group TDSJ and a control group (celecoxib capsules in combination with thalidomide tablets) for 8 weeks. Visual analogue scale, bath ankylosing spondylitis disease activity index, bath ankylosing spondylitis functional index, and traditional Chinese medicine syndrome scores will be used as primary indicators. Erythrocyte sedimentation rate, C-reactive protein, spinal mobility (figure-ground distance, occipital tubercle-wall distance, Schober test) will be used as secondary indicators. Vital signs (respiration, heart rate, body temperature, blood pressure, electrocardiogram), blood routine, urine routine, stool routine, liver function, and renal function will be used as safety indicators. The primary and secondary indicators will be detected at 0th and 8th week, while safety indicators at 0th, 4th, and 8th week. DISCUSSION: This study will provide high-quality clinical evidence for the efficacy and safety of TDSJ in the treatment of AS.

Ovalbumin fibril-stabilized oleogel-based Pickering emulsions improve astaxanthin bioaccessibility.

The present study aimed to enhance the bioaccessibility of hydrophobic astaxanthin (AST) by developing food-grade emulsion systems. Ovalbumin (OVA) fibrils and candelilla wax-based oleogels were prepared for the next fabrication of AST-loaded oleogel-based Pickering emulsions. The food-grade oleogel was obtained by mixing 0.7% (w/w) candelilla wax and soybean oil. The nano-scale OVA fibrils were observed by transmission electron microscope. SDS-PAGE analysis of OVA fibrils displayed the appearance of peptides with molecular weight around 10 kDa. Contact angle measurement indicated that excellent amphiphilicity endowed OVA fibrils with satisfactory Pickering emulsifier performance. The obtained oleogel-based Pickering emulsions displayed ultrastability during 90-day storage and outstanding freeze-thaw stability. Furthermore, the superiority of AST-loaded oleogel-based Pickering emulsion was further reflected in the apparently ameliorative lipolysis extent and AST bioaccessibility compared with oleogel. This work would facilitate the utilization of OVA and the development of oleogel-based Pickering emulsions with desirable nutraceutical bioaccessibility.

Two-Pronged Intracellular Co-Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy.

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid-coated iron oxide nanoparticle is delivered as nanovaccine (IONP-C/O@LP) that can co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enables IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen-specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo.

HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery.

Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery.