BackgroundParathyroid hormone (PTH) is required for the maintenance of normal bone physiology. This study describes the properties of a sustained-release formulation of recombinant human PTH (rhPTH) using chitosan and silk fibroin microparticles as carriers for drug delivery, developed using a spray-drying method.Material/MethodsChitosan, silk fibroin, and chitosan/silk fibroin microparticles loaded with rhPTH were studied with scanning electron microscopy (SEM) to estimate the particle size and surface morphology. The in vitro release of rhPTH was used to assess the developed formulation. The effect of the spray-drying process was assessed by powder X-ray diffraction (PXRD) of the microparticles. Quantification of the released rhPTH was performed by enzyme-linked immune sorbent assay (ELISA). Fourier-transform infrared spectroscopy (FTIR) was used to determine the differences in the absorption frequency of samples.ResultsSurface morphology of the final formulation showed the absence of pure crystals of chitosan and silk fibroin in the final formulation and FTIR demonstrated electrostatic interactions between chitosan and silk fibroin, which was supported by PXRD. The chitosan/silk fibroin microparticles loaded with rhPTH showed an entrapment efficiency (EE) that ranged from 60.36–72.99% with a 50% rhPTH release profile at pH 7.5 in 24 hours. There was no particle aggregation in blood and little hemolysis, indicating stability of the rhPTH-loaded microparticles.ConclusionsA silk fibroin/chitosan microparticle formulation loaded with rhPTH was shown to be stable and to provide sustained-release of rhPTH, supporting a potential role of this formulation in the treatment of bone diseases including osteoporosis and bone fracture.

The Chinese concave‐eared torrent frog (Odorrana tormota) is typically sexually dimorphic. Females are significantly less common than males in the wild. Until now, the molecular mechanisms of reproduction and sex differentiation of frogs remain unclear. Here, we integrated mRNA and microRNA (miRNA) expression profiles to reveal the molecular mechanisms of reproduction and sex differentiation in O. tormota. We identified 234 differentially expressed miRNAs (DEMs) and 18,551 differentially expressed transcripts. Of these, 12,053 mRNAs and 64 miRNAs were upregulated in testes, and 6,498 mRNAs and 170 miRNAs were upregulated in ovaries. Integrated analysis of the miRNA and mRNA expression profiles predicted 75,602 potential miRNA–mRNA interaction sites, with 42,065 negative miRNA–mRNA interactions. We found 36 differentially expressed genes (DEGs) related to reproduction and sex differentiation, of which 15 DEGs formed 92 negative miRNA–mRNA interactions with 34 known DEMs. Thus, miRNAs may play other important roles in O. tormota. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed reproductive‐related processes, such as the gonadotropinreleasing hormone signaling pathway and ovarian steroidogenesis. Based on functional annotation and the literature, the retinoic acid signaling pathway, the SOX9–AMH pathway, and the process of spermatogenesis may be involved in the molecular mechanisms of reproduction and sex differentiation in O. tormota, and may be regulated by miRNAs. The miRNA–mRNA pairs described may provide further understanding of the regulatory mechanisms associated with reproduction and sex differentiation, and the molecular mechanism of reproduction in O. tormota.

Purpose: To enhance the clinical effectiveness of paclitaxel (PTX) by co-delivery with ursolic acid (UA) for the treatment of head and neck cancer Methods: Co-loaded liposomes of PTX and UA (UA-PTX-LiP) were prepared by thin-film hydration method. Their size and loading efficiency were determined using dynamic light scattering (DLS) technique and high performance liquid chromatography (HPLC), respectively. The effectiveness of UA-PTX-LiP against HSC-3 human head and neck cancer cell-lines was compared with that of PTX liposome (PTX-LiP) using systemic cell-based in vitro evaluation with MTT assay. Fluorescent microscopy was used for cell uptake studies. Results: The size of the prepared UA-PTX-LiP was 126.5 ± 3.22 nm. The ratiometric system for PTX and UA as liposomes revealed significantly enhanced cytotoxicity, with comparatively lower IC50, when compared to individual PTX-Lip. Fluorescent microscopy revealed the internalization ability of UA-PTX-LiP by targeted delivery of PTX in HSC-3 human head and neck cancer cell-line. Conclusion: These results show that UA-PTX-LiP successfully enhances the therapeutic potential and clinical outcomes of PTX in head-and-neck cancer, and also demonstrate the useful effect of combination of UA and PTX in chemotherapy.

ON THE COVER: The cover image is based on the Research Article Integrated mRNA and miRNA expression profile analyses reveal the potential roles of sex‐biased miRNA‐mRNA pairs in gonad tissues of the Chinese concave‐eared torrent frog (Odorrana tormota) by Yilin Shu et al., https://doi.org/10.1002/jez.b.22851. Cover image © Yilin Shu.