Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.
Probiotics which enhance the biosynthesis of 5-hydroxytryptamine in enterochromaffin cells could alleviate depression symptoms through regulating the CREB-BDNF pathway in the brain.
Human leukocyte antigen-G (HLA-G) expression in 55 cervical intraepithelial neoplasia (CIN) patients with or without human papillomavirus (HPV) infection and 116 patients with squamous cell cervical cancer were examined using immunohistochemistry. Host immune response was assessed by estimating the number of intratumoral lymphocyte infiltration (TIL) in all lesions and counting CD57-expressing cells in the neoplasm lesions. The means of HLA-G immunoreactive scores were compared by the Mann-Whitney test and 1-way analysis of variance (ANOVA). The association of HLA-G expression with disease progression, HPV infection and host immune response was calculated using the Pearson Chi-square test. It was found that HLA-G expression increasingly progressed from patients with CIN 1 to CIN 2/3 and was highest in patients with cervical cancer. Human leukocyte antigen-G expression was also significantly higher in CIN and cancer patients with HPV 16/18 than in CIN patients without HPV. A significant correlation between HLA-G expression and TIL score or the counting of CD57-expressing cells was also evident in CIN patients with HPV infection and cervical cancer cases. These results suggest that HLA-G expression in cervical lesions is associated with carcinogenesis, HPV infection, and host immune response.
G-protein-coupled receptor 48 (GPR48) is an orphan receptor belonging to the G-protein-coupled receptors family, which plays an important role in the development of various organs and cancer development and progression such as gastric cancer and colorectal cancer (CRC). However, the prognostic value of GPR48 expression in patients with CRC has not been reported. In this study, we observed that GPR48 was overexpressed in primary CRC and metastatic lymph nodes and closely correlated with tumor invasion and metastasis. Multivariate analysis indicated that high GPR48 expression was a poor prognostic factor for overall survival in CRC patients. In vitro and in vivo assays demonstrated that enforced expression of GPR48 contributed to enhance migration and invasion of cancer cells and tumor metastasis. In addition, we found that GPR48 increased nuclear β-catenin accumulation, T-cell factor 4 (TCF4) transcription activity, and expression of its target genes including Cyclin D1 and c-Myc in CRC cells. Correlation analysis showed that GPR48 expression in CRC tissues was positively associated with β-catenin expression. Upregulation of GPR48 resulted in increased phosphorylation of glycogen synthase kinase 3β, Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) in CRC cells, while inhibition of PI3K/Akt and mitogen-activated protein kinase /ERK1/2 pathways was sufficient to abolish the effect of GPR48 on β-catenin/TCF signaling. Taken together, GPR48 could serve as both a prognostic biomarker and a therapeutic target for resectable CRC patients.
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