Biao Chen

Extra bilirubin in the blood can provoke serious illness in patients with severe liver disease. Hemoperfusion is an effective method to remove the extra bilirubin, but its application is limited by the low adsorption efficiency and poor biocompatibility of available adsorbent materials. In this study, chitin/ordered mesoporous carbon CMK3 (Ch/CMK3) microspheres are successfully prepared. Results of characterization experiments indicated that these composite microspheres possess a multilayered porous nanofibrous structure with an extremely large specific surface area (300.19 m² g⁻¹) and large pore size. Notably, the Ch/CMK3 microspheres demonstrated a high bilirubin adsorption capacity (228.19 mg g⁻¹) in phosphate buffer solution (PBS), and an outstanding bilirubin removal ratio (76.78% ± 4.40%) in the plasma of rabbits with hyperbilirubinemia without affecting the protein components. More importantly, the Ch/CMK3 microspheres showed no effect on other blood components, no cytotoxicity, and no systemic toxicity to mice. Cell co‐culture experiments revealed that the microspheres can provide a 3‐dimensional (3D) space to promote cell adhesion, proliferation, and nutrient exchange. These Ch/CMK3 microspheres featuring a strong ability for bilirubin adsorption and good biocompatibility can be a promising candidate in biomedical applications such as hemoperfusion, cell microcarrier, and 3D tissue engineering.

Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self‐esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate‐severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein–protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, LCN2, PTGES, and GDF15 were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; CCL2 originated from activated TNF signaling pathway and S100A7 could be related with “acne‐flare”. While treating with isotretinoin for 8 weeks, key genes were downregulated, including HMGCS1, HMGCR, FDFT1, MVD, IDI1, and FDPS, which may be associated with decreased sebum synthesis; HMGCS1, HMGCR, and FDFT1 also probably associated with apoptosis of sebocytes. There were only two common genes including ACSBG1 and BCAT2 which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid‐like compounds with similar curative effect and without teratogenicity.

Mycosis Fungoides (MF) is the most common subtype of cutaneous T‐cell lymphomas (CTCL). Shank‐associated RH domain‐interacting protein (SHARPIN) participates in the initiation and development of multiple tumors. However, the clinical significance of SHARPIN in MF hasn't been investigated. The c‐Jun N‐terminal kinases (JNKs) pathway is a member of mitogen‐activated protein kinases (MAPKs). Its dysregulation is observed in various tumors including CTCL, whereas the roles of JNKs pathway in MF remain largely unknown, the relationship between SHARPIN and JNKs pathway remains elusive. Herein, we showed that up‐regulated expression of SHARPIN was related to poor prognosis of MF patients. In vitro experiments found increased SHARPIN expression and activation of JNKs pathway in MF cell line MyLa2059. SHARPIN induced transforming growth factor β activated kinase‐1 (TAK1) transcription, which is an upstream kinase of JNKs, NF‐κB and p38 pathway, leading to activation of JNKs and NF‐κB pathway. SHARPIN also promoted p38 signaling independent of TAK1 expression, by which overexpression of SHARPIN induced cell proliferation, inhibited apoptosis, enhanced migration and invasion of MyLa2059. Our work provided direct evidences for effects of SHARPIN on JNKs and NF‐κB pathway, and the contributing roles of JNKs, NF‐κB and p38 pathway regulated by SHARPIN in the development of MF.