Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To analyze the correlation between different types of anemia(small cell anemia and nor-mal cell anemia)before operation and pathological features and prognosis of colorectal cancer patients.Methods The clinical data of 130 patients with colorectal cancer who underwent radical surgery in our hospital from March 2018 to February 2021 were retrospectively analyzed.According to the morphology of red blood cells,the patients were divided into group A(70 cases without anemia),group B(18 cases with small cell anemia)and group C(42 cases with normal cell anemia).Pathological features and postoperative 2 a survival rate of the 3 groups were compared.The correlation between preoperative anemia types and pathological features of colorectal cancer was analyzed by Phi coefficient test,and Kaplan-Meier survival curve was drawn to compare the survival rate of the 3 groups.Results There were significant differences in gender,tumor site,tumor diameter and TNM stage distribution among the three groups(P<0.05).The Phi coefficient test showed that preoperative anemia type was correlated with gender,tumor site,tumor diameter,and TNM stage(r = 0.238,0.255,0.266,0.331,P = 0.025,0.015,0.010,0.001).Multivariate Logistic regression analysis showed that tumor diameter≥5 cm,TNM stage Ⅲ-Ⅳ,distant metastasis,lymph node metastasis,preoperative small cell anemia,preoperative normal cell anemia were the risk factors for the prognosis of colorectal cancer after radical surgery(OR>1,P<0.05).The overall survival rate of 2a in group A was higher than that in group C>that in group B(P<0.05).Log-rank test showed that the postoperative survival rate of the three groups was significantly different(P<0.05).Conclusion Preoperative anemia types were correlated with tumor site,tumor diameter,TNM stage and postoperative survival time of colorectal cancer patients,among which preoperative small-cell anemia patients had the lowest survival rate.

In recent years, peptide self-assembly has received much attention because of its ability to form regular and ordered structures with diverse functions. Self-assembled peptides can form aggregates with defined structures under specific conditions. They show different characteristics and advantages (e.g., good biocompatibility and high stability) compared with monomeric peptides, which form the basis for potential application in the fields of drug delivery, tissue engineering, and antiseptics. In this paper, the molecular mechanisms, types and influencing factors of forming self-assembled peptides were reviewed, followed by introducing the latest advances on fibrous peptide hydrogels and self-assembled antimicrobial peptides. Furthermore, the challenges and perspectives for peptide self-assembly technology were discussed.
Drug Delivery Systems ; Hydrogels ; Peptides ; Tissue Engineering

Objective To explore the application of optical coherence tomography in vascular tissue engineering culture by dynamic monitoring its changes.Methods Human umbilical artery smooth muscle cells were isolated and culture by tissue block method.After passage culture and cell surface markers evaluation, smooth muscle cells were seeded onto polyglycolic acid scaffold and placed into the bioreactor based on Luo-Ye pump with pulsatile stress for three-dimensional culture.At 1、4、 7 、10、14、17、21 days in culture, the image data was obtained by optical coherence tomography technology.The ability of imaging TEBV via OCT was analyzed combined with histopathological observation.Results As the incubation time extended,OCT clearly showed PGA gradual degradation, decreased composite scaffold thickness and the wall structure from loose to tight.At 21 days in culture, the vessel mimics had smooth surface with extracellular matrix evenly distributed and achieved complete reconstruction in the PGA scaffold.Combining with histopathological staining, the blood vessel mimics were similar to natural blood vessels.OCT measured TEBV thickness compared with histopathological measurement had good correlation (r =0.922,P ＜ 0.05).Conclusion Optical coherence tomography could clearly image microstructures of tissue engineered blood vessels cultured in three-dimensional culture system based on Luo-Ye pump, delineate the reconstruction of TEBV-like tissue in the bioreactor and provide as a dynamic and convenient monitoring tool in vascular tissue engineering.