BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Periodontitis is a chronic inflammatory disease characterized by progressive destruction of alveolar bone.The most critical mechanism underlying alveolar bone destruction is the imbalance of bone homeostasis,where osteoblast-mediated bone matrix synthesis plays an important role in regulating bone homeostasis.Regulated cell death is instrumental in both the inflammatory microenvironment and the regulation of bone homeostasis.Chronic inflammation,oxidative stress,and other factors can be directly involved in mitochondrial and death receptor-mediated signaling pathways,modulating B-cell lymphoma 2 family proteins and cysteine aspartic acid specific protease(caspase)activity,thereby affecting osteoblast apoptosis and alveolar bone homeostasis.Chronic inflammation and cellular damage induce osteoblast necroptosis via the RIPK1/RIPK3/MLKL signaling pathway,exacerbating the inflammatory response and accelerating alveolar bone destruction.Stimuli such as pathogenic microorganisms and cellular injury may also activate caspase-1-dependent or independent signaling pathways and gasdermin D family proteins,promoting osteoblast pyroptosis and releasing pro-inflammatory cytokines to mediate alveolar bone damage.Iron overload and lipid peroxidation in periodontitis can trigger ferroptosis in osteoblasts,impacting their survival and function,ultimately leading to bone homeostasis imbalance.This article focuses on the mechanism of periodontal disease affecting bone homeostasis through regulatory cell death,aiming to provide research evidence for the treatment of periodontitis and alveolar bone homeostasis imbalance.

Iron metabolism refers to the process of absorption,transport,excretion and storage of iron in organisms,including the biological activities of iron ions and iron-binding proteins in cells.Clinical research and animal experiments have shown that iron metabolism is associated with the progress of periodontitis.Iron metabolism not only enhances the proliferation and toxicity of periodontal pathogens,but also activate host immune-inflammatory response mediated by macrophages,neutrophils and lymphocytes.In addition,iron metabolism is also involved in regulating cellular death sensitivity of gingival fibroblasts and osteoblasts and promoting the differentiation of osteoclasts,which plays a regulatory role in the regeneration and repair of periodontal tissue.This article reviews the research progress on the pathogenesis of periodontitis from the perspective of iron metabolism,aiming to provide new ideas for the treatment of periodontitis.

Urinary system tumors include malignancies of the bladder, kidney, and prostate, and present considerable challenges in diagnosis and treatment. The conventional therapeutic approaches against urinary tumors are limited by the lack of targeted drug delivery and significant adverse effects, thereby necessitating novel solutions. Intelligent nanomedicine has emerged as a promising therapeutic alternative for cancer in recent years, and uses nanoscale materials to overcome the inherent biological barriers of tumors, and enhance diagnostic and therapeutic accuracy. In this review, we have explored the recent advances and applications of intelligent nanomedicine for the diagnosis, imaging, and treatment of urinary tumors. The principles of nanomedicine design pertaining to drug encapsulation, targeting and controlled release have been discussed, with emphasis on the strategies for overcoming renal clearance and tumor heterogeneity. Furthermore, the therapeutic applications of intelligent nanomedicine, its advantages over traditional chemotherapy, and the challenges currently facing clinical translation of nanomedicine, such as safety, regulation and scalability, have also been reviewed. Finally, we have assessed the potential of intelligent nanomedicine in the management of urinary system tumors, emphasizing emerging trends such as personalized nanomedicine and combination therapies. This comprehensive review underscores the substantial contributions of nanomedicine to the field of oncology and offers a promising outlook for more effective and precise treatment strategies for urinary system tumors.

To analyze the global burden of periodontal disease and its relation with socioeconomic development. Data of global disability-adjusted life year (DALY) due to periodontal disease and human development index (HDI) from 1990 to 2019 were obtained from Global Health Data Exchange (GHDx) and human development reports. The trend of the global burden of periodontal disease from 1990 to 2019 was described. The correlation between age-standardized DALY rates and HDI were examined in 2019, and between-country periodontal disease burden inequality from 1990 to 2019 was measured using health-related Gini coefficients and concentration indexes. From 1990 to 2019, the global DALY rate due to periodontal disease increased from 78.63 to 85.48, and the epidemiological burden did not increase significantly. Statistical differences were found across different HDI categories for age-standardized DALY rates of periodontal disease ( 44.315, <0.01) in 2019. Linear regression analysis also revealed a negative correlation between age-standardized DALY rate of periodontal disease and HDI ( = -0.417, <0.01) . Gini coefficients decreased from 0.361 to 0.281 and concentration indexes fell from 0.0339 to -0.0538 between 1990 and 2019. The global burden of periodontal disease did not increase between 1990 and 2019, though the socioeconomic-associated inequality still existed. The burden of periodontal disease was more concentrated in less developed countries, and the socioeconomic-associated inequality has increased since 2000.
Disability-Adjusted Life Years ; Global Health ; Humans ; Periodontal Diseases/epidemiology* ; Quality-Adjusted Life Years ; Socioeconomic Factors

Streptococcus mutans (S. mutans) is generally regarded as a major contributor to dental caries because of its ability to synthesize extracellular polysaccharides (EPS) that aid in the formation of plaque biofilm. The VicRKX system of S. mutans plays an important role in biofilm formation. The aim of this study was to investigate the effects of vicK gene on specific characteristics of EPS in S. mutans biofilm. We constructed single-species biofilms formed by different mutants of vicK gene. Production and distribution of EPS were detected through atomic force microscopy, scanning electron microscopy and confocal laser scanning microscopy. Microcosmic structures of EPS were analyzed by gel permeation chromatography and gas chromatography-mass spectrometry. Cariogenicity of the vicK mutant was assessed in a specific pathogen-free rat model. Transcriptional levels of cariogenicity-associated genes were confirmed by quantitative real-time polymerase chain reaction. The results showed that deletion of vicK gene suppressed biofilm formation as well as EPS production, and EPS were synthesized mostly around the cells. Molecular weight and monosaccharide components underwent evident alterations. Biofilms formed in vivo were sparse and contributed a decreased degree of caries. Moreover, expressional levels of genes related to EPS synthesis were down-regulated, except for gtfB. Our report demonstrates that vicK gene enhances biofilm formation and subsequent caries development. And this may due to its regulations on EPS metabolism, like synthesis or microcosmic features of EPS. This study suggests that vicK gene and EPS can be considered as promising targets to modulate dental caries.
Animals ; Biofilms ; Dental Caries ; Dental Plaque ; Rats ; Streptococcus mutans/genetics*

Background and purpose: XB130 protein plays an important role in proliferation and invasiveness of tumor cells. However, there is little research on the role of XB130 protein in hepatocellular carcinoma (HCC) and the effect of XB130 is still unclear. This study investigated the role of XB130 gene in the proliferation of HCC cell and its potential mechanism. Methods: The protein expressions of XB130 in HCC cell lines, Huh7, HepG2 and SNU449, and liver cell line HL7702 were detected by Western blot. Huh7 cells were transfected with XB130-siRNA. Then cell viability was measured using cell counting kit-8 (CCK-8), and cell cycle was examined by flow cytometry. Protein expressions of p-AKT, p-GSK3β, cyclin D1 and p-Rb were detected by Western blot, while mRNA expression levels of E2F/DP1 target genes (cyclin E1, c-Myc and PCNA) were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results: The relative protein expressions of XB130 in Huh7, HepG2, SNU449 and HL7702 cells were 0.66±0.10, 0.78±0.11, 0.83±0.08 and 0.32±0.06, respectively. The difference between HCC cell lines and HL7702 cell line was statistically significant (P＜0.01). The transfection efficacy of XB130-siRNA was confirmed to be highly effective in Huh7 cells, and the viability of XB130-siRNA transfected Huh7 cells declined 72 h after transfection (P＜0.001). The ratio of Huh7 cells in G0/G1 phase was increased, while the ratio in S or G2/M was decreased 48 h after XB130-siRNA transfection (P＜0.01). In addition, compared with negative control, protein expressions of p-AKT, p-GSK3β, cyclin D1 and p-Rb, and mRNA expression levels of cyclin E1, c-Myc and PCNA were all decreased in XB130-siRNA transfected Huh7 cells (P＜0.001). Conclusion: XB130 promotes the proliferation of HCC cells by regulating cell cycle-related proteins and downstream transcription factors.

Objective To explore the correlation between resistins rs2161490and rs1423096 genotype with type 2 diabetes mellitus (T2DM)in Guangdong.Methods Collected 178 blood of newly diagnosed T2DM in the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to November 2015 as the patient group and 192 blood of healthy physi-cal examination as the control group.Analysis of the two groups of gene distribution frequency was to reach the genetic equi-librium,comparative two gene loci frequencies of resistin rs2161490 and rs1423096 in case group and control group was sta-tistically significant,and compared the distribution frequency of rs2161490 locus T→C and rs1423096 locus A→G between the patient group and the control group.Then made a logistic regression analysis:analysing the risk two loci each genotype of resistin rs2161490 and rs1423096 to T2DM,adjust of the gender and age,and the changes of the risk of the two variables. Comparative blood lipids biochemical indexes between case group and the control group,mode the correlation analysis be-tween TG,CHOL,HDL-C and LDL-C levels of serum lipids in patients with rs2161490 and rs1423096 each genotypewere performed.Results The sample was consistent with Weinberg Hardy’s law of inheritance,which was representative of the population,comparing two gene loci frequency of resistin rs2161490 and rs1423096 of case group and control group:com-parinng CT,TT,CC of rs2161490 genotype,there was no statistically significant difference (P=0.834,>0.05),and com-parinng AA,AG,GG of rs2161490 genotype,there was no statistically significant difference (P=0.960,>0.05).Each gen-otypes with T2DM risk analysis,there was no statistically significant difference(P>0.05).Adjusting the risk change after the two variables,gender and age,there was no statistically significant difference (P>0.05);TG,CHOL,HDL-C and LDL-C in each of the genes expression levels correlation analysis,there was no statistically significant difference (P>0.05).Con-clusion Analysis results showed that the frequency of two loci all genotypes in the case group and control group were no statistical significance (P>0.05).The risk of two loci gene type of rs2161490 with rs1423096 and type 2 diabetes were be-fore and after the covariate adjustment had no statistical significance (P>0.05 ).Each genotype of rs2161490 with rs1423096 and lipid levels had no statistical significance (P>0.05).Thus infer that two genotypes is not risk for type 2 dia-betes genes in guangdong area.