Molecular design, construction and analgesic mechanism insights into the novel transdermal fusion peptide ANTP-BgNPB.

Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.

Artificial Light-Harvesting Metallacycle System with Sequential Energy Transfer for Photochemical Catalysis.

Highly efficient light-harvesting systems with the sequential energy transfer process are significant for utilizing solar energy in photosynthesis. Herein, we report a quadrilateral platinum(II) metallacycle containing tetraphenylethylene (M1) as a light-harvesting platform. The M1 assembly serves as an ideal donor because of the aggregation-induced emission (AIE) effect, realizing two-step sequential energy transfer from the M1 assembly to eosin Y (ESY) and then to sulforhodamine (SR101) with high efficiency. ESY was used as a bridge in a relay mode during this process. To better mimic natural photosynthesis, the M1-ESY-SR101 system was utilized as photochemical catalysis for alkylation of C-H bonds in aqueous solution, showing enhanced catalytic activity as compared with the M1-ESY system or ESY/SR101 alone.

miR-30c affects the pathogenesis of ulcerative colitis by regulating target gene VIP.

MicroRNAs play a crucial role in regulating the epithelial barrier and immune response, which are implicated in the pathogenesis of ulcerative colitis (UC). This study aimed to investigate the role and molecular mechanism of miR-30c in the pathogenesis of UC using a dextran sulfate sodium salt (DSS)-induced colitis model, which is similar to ulcerative colitis. Wild-type (WT) and miR-30c knockout (KO) mice were assigned to either control or DSS-treated groups to evaluate the influence of aberrant miR-30c expression on UC pathogenesis. The disease activity index, inflammatory factors, and the extent of pathological and histological damage in colon tissues were analyzed. The effect of miR-30c on vasoactive intestinal peptide (VIP) gene expression was validated through luciferase reporter assay, qRT-PCR, Western blotting, and immunohistochemistry. The results showed that miR-30c KO mice with DSS-induced colitis model showed more severe phenotypes: significantly higher disease activity indices, significant body weight loss, reduced length of the colon of mice, increased number of aberrant crypt structures, reduced mucus secretion, and significant differences in inflammatory factors. These findings suggested that the absence of miR-30c might promote DSS-induced colitis, and the targe-regulatory effect of miR-30c on VIP might play an important role in the development of colitis.

MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression.

Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to investigate the significance of MKRN1 in cervical cancer and explore its potential as a diagnostic marker and therapeutic target. The results indicated that MKRN1 expression was up-regulated in cervical cancer tissues and correlated with advanced tumor stage, higher grade, and poor patient survival. Functional studies demonstrated that targeting MKRN1 effectively inhibited cell proliferation, migration, and invasion, highlighting its critical role in tumor progression and metastasis. Moreover, the knockdown of MKRN1 resulted in altered expression patterns of six transcription factor-encoding genes, revealing its involvement in gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying the effects of MKRN1 knockdown on gene expression. Furthermore, the results suggested that MKRN1 might serve as a diagnostic marker for personalized treatment strategies and a therapeutic target to inhibit tumor growth, metastasis, and overcome drug resistance. The development of MKRN1-targeted interventions might hold promise for advancing personalized medicine approaches in cervical cancer treatment. Further research is warranted to validate these findings, elucidate underlying mechanisms, and translate these insights into improved management and outcomes for cervical cancer patients.

Endoplasmic reticulum stress affected chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers.

In our previous study, chondrocyte apoptosis in femoral head necrosis (FHN)-affected broilers was found to be associated with the endoplasmic reticulum stress (ERS) signaling pathway. In the present study, we further explored the role of ERS-induced chondrocyte apoptosis in FHN-affected broilers and the parallel test was carried out with articular chondrocytes cultivated in vitro. The broilers and chondrocytes were treated with methylprednisolone (MP). The main pathological changes in FHN-affected broilers included the proximal femoral head separated from its articular cartilage and growth plate lesions. MP-treated chondrocytes demonstrated morphology changes, cell viability reduction, secretory capacity dysfunction, and apoptosis. The mRNA expressions of pro-apoptotic genes controlled by ERS signaling pathway were up-regulated both in vivo and in vitro experiments. It showed that MP induced FHN in broilers, activated apoptosis-related genes on ERS signaling pathway, and affected the survival and apoptosis of chondrocytes, and bone growth.