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Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

Abstract Background Traditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments. Materials and methods Targeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved. Results These biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth. Conclusions The aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).

Abstract Introduction Pancreaticobiliary reflux (PBR) can induce gallstone formation; however, its pathogenic mechanism remains unclear. In this study, we explored the mechanism of PBR by the non-targeted metabolomic analysis of bile in patients with PBR. Objective The aim of this study was to investigate the pathogenic mechanism in PBR by the non-targeted metabolomic analysis of bile collected during surgery. Methods Sixty patients who underwent gallstone surgery at our center from December 2020 to May 2021 were enrolled in the study. According to the level of bile amylase, 30 patients with increased bile amylase ( > 110 U/L) were classified into the PBR group, and the remaining 30 patients were classified into the control group (≤ 110 U/L). The metabolomic analysis of bile was performed. Results The orthogonal projections to latent structure-discriminant analysis of liquid chromatography mass spectrometry showed significant differences in bile components between the PBR and control groups, and 40 metabolites were screened by variable importance for the projection value (VIP > 1). The levels of phosphatidylcholine (PC) and PC (20:3(8Z,11Z,14Z)/14:0) decreased significantly, whereas the levels of lysoPC (16:1(9z)/0:0), lysoPC (15:0), lysoPC (16:0), palmitic acid, arachidonic acid, leucine, methionine, L-tyrosine, and phenylalanine increased. Conclusions Significant differences in bile metabolites were observed between the PBR and control groups. Changes in amino acids and lipid metabolites may be related to stone formation and mucosal inflammation.

Abstract Background Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized. Methods The expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting. Results Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis. Conclusions CAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future.

An eco-friendly biosynthesized Ag NPs immobilized Hibiscus rosa-sinensis extract has been introduced. The as-prepared nanoparticles were characterized using UV–Vis, SEM, and FT-IR analysis. In the FT-IR test, the presence of many antioxidant compounds with related bonds caused the excellent condition for reducing of silver in the silver nanoparticles. In UV–Vis, the clear peak in the wavelength of 428 nm indicated the formation of silver nanoparticles. The synthesized nanoparticles had very low cell viability and high anti-liver cancer activities dose-dependently against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cell lines without any cytotoxicity on the normal cell line (HUVEC). The synthesized nanoparticles inhibited half of the DPPH molecules in the concentration of 78 µg/mL. Perhaps notable anti-liver cancer activities of the synthesized nanoparticles against common liver cancer cell lines are linked to their antioxidant activities.