Thermosensitive hydrogel with programmed dual-octenidine release combating biofilm for the treatment of apical periodontitis.

The utilization of intracanal medicaments is an indispensable procedure in root-canal treatment. However, the conventional intracanal medicaments still need improvement regarding antimicrobial efficacy and ease of clinical operation. To address the above issues, OCT/PECT@OCT + ALK composite hydrogel characterized by programming sequential release of dual antimicrobial agents has been proposed. Thanks to the self-assemble ability of amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), dual hydrophilic and hydrophobic antimicrobial agents could be easily encapsulated in the hydrogel system and tailored for sequential drug release for a better antibiofilm effect. The hydrophilic octenidine (Octenidine dihydrochloride, OCT-HCl) is encapsulated in the hydrophilic part of hydrogel for instantaneous elevating the drug concentration through bursting release, and the hydrophobic octenidine (Octenidine, OCT) is further loaded into the PECT nanoparticles to achieve a slower and sustained-release profile. Additionally, calcium hydroxide (Ca(OH)2) was incorporated into the system and evenly dispersed among PECT nanoparticles to create an alkaline (ALK) environment, synergistically enhancing the antibiofilm effect with higher efficiency and prolonged duration. The antibiofilm effect has been demonstrated in root-canal models and apical periodontitis rats, exhibiting superior performance compared to clinically used Ca(OH)2 paste. This study demonstrates that OCT/PECT@OCT + ALK composite thermosensitive hydrogel is a potential intracanal medicament with excellent antibiofilm effect and clinical operability.

Effects of phase-transited lysozyme on adhesion, migration and odontogenic differentiation of human dental pulp cells: An in vitro study.

AIM: To explore the effects of phase-transited lysozyme (PTL) coated dentine slices on cell adhesion, migration and odontogenic differentiation of human dental pulp cells (HDPCs). METHODOLOGY: Cell growth and cell cycle analysis were conducted to verify the biocompatibility of PTL for HDPCs. Cell adhesion, cell morphology and proliferation were explored by DiI staining, Scanning electron microscopy and MTT assay. Cell migration was investigated by Transwell assay. The effects of PTL on odontogenesis and mineralization of HDPCs were assessed by real-time quantitative polymerase chain reaction and Western blot. The mineralization of HDPCs was evaluated by Alizarin red staining. HDPCs were isolated from extracted third molars. The level of statistically significant difference was accepted at p < .05. RESULTS: PTL showed no negative effect on cell cycle of HDPCs and compared with the blank group, HDPCs labelled with DiI staining showed significantly more adhered cells at 48 h (p < .05), extending cell processes and more finger-like or reticular pseudopodia on PTL-coated dentine slices. The results of MTT and Transwell assay showed that PTL promoted the proliferation (p < .05) and migration (p < .01) of HDPCs, respectively. Compared with the blank group, the gene expression of dentine sialophosphoprotein (DSPP), osteopontin and bone sialoprotein in HDPCs cultured on PTL was significantly upregulated on day 3 and 7 (p < .05), while the protein expression of DSPP showed no significant change on both day 7 and day 14. Alizarin red staining showed that PTL promoted more mineralization nodules formation of HDPCs (p < .05). CONCLUSIONS: PTL promoted the adhesion, proliferation and migration of HDPCs on dentine slices, and positively affected odontogenic differentiation and mineralization of HDPCs.

Depressive symptoms increase the risk of falls and injurious falls in Chinese adults aged ≥ 45 years: A 3-year cohort study.

Background: Falls and depressive symptoms are both public health concerns in China, but the effects of depressive symptoms on falls and injurious falls have not been thoroughly investigated. Methods: This population-based prospective cohort study used data derived from adults aged ≥45 years acquired from the 2015 and 2018 China Health and Retirement Longitudinal Study. Data were analyzed from August 2021 to December 2021. Self-reported depressive symptoms were determined using a 10-item Center for Epidemiologic Studies Depression scale (CESD-10) with a total score range of 0-30. Item responses of 3-4 or 5-7 days were deemed indicative of specific depressive symptoms. The outcome variables were self-reported accidental falls and injurious falls. Results: Of the 12,392 participants included in the study, 3,671 (29.6%) had high baseline depressive symptoms (CESD-10 scores ≥ 10), 1,892 (15.3%) experienced falls, and 805 (6.5%) experienced injurious falls during 2015-2018 follow-up. High depressive symptoms increased the risk of falls [odds ratio (OR) 1.34, 95% confidence interval (CI) 1.19-1.50] and injurious falls (OR 1.28, 95% CI 1.09-1.51) in a multivariable logistic regression model adjusted for major demographic, health-related, and anthropometric covariates. All of the 10 specific depressive symptoms except "felt hopeless" were associated with falls, and four specific symptoms significantly increased the risk of injurious falls; "had trouble concentrating" (OR 1.32, 95% CI 1.13-1.55); "felt depressed" (OR 1.32, 95% CI 1.12-1.55); "everything was an effort" (OR 1.23, 95% CI 1.04-1.45); and "restless sleep" (OR 1.18, 95% CI 1.02-1.40). Conclusion: High depressive symptoms are significantly related to risk of falls and injurious falls. Four specific symptoms (had trouble concentrating, felt depressed, everything was an effort, and restless sleep) increase the risk of injurious falls in Chinese adults aged ≥ 45 years.

A Strategy Study on Risk Communication of Pandemic Influenza: A Mental Model Study of College Students in Beijing.

PURPOSE: To understand the characteristics of risk perception of influenza pandemic in college students with prominent frequency and the differences between these risk perceptions and professionals. Then, offering a proposal for the government to improve the efficiency of risk communication and health education. METHODS: According to the mental model theory, researchers first draw a framework of key risk factors, and then they ask these students about the understanding of the framework with questionnaire and then making concept statistics and content analysis on the respondents' answers. RESULTS: Researchers find some students' misunderstanding of pandemic including excessive optimism to the consequences of a pandemic, a lack of detailed understanding of mitigation measures, and negative attitudes towards health education and vaccination. Most students showed incomplete and incorrect views about concepts related to the development and exposure factors, impact and mitigation measures. Once threatened, it may lead to the failure of decision-making. The majority of students we interviewed had positive attitudes towards personal emergency preparedness for a pandemic influenza and specialized health education in the future. CONCLUSION: Researchers suggest that the government should make a specific pandemic guidance plan by referring to the risk cognitive characteristics of college students shown in the research results, and update the methods of health education to college students.

Knockdown of Upregulated Gene 11 (URG11) Inhibits Proliferation, Invasion, and ß-Catenin Expression in Non-Small Cell Lung Cancer Cells.

Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X protein, was found to be involved in the development and progression of several tumors. However, the role of URG11 in human non-small cell lung cancer (NSCLC) has not yet been determined. Therefore, the aim of the present study was to explore the role of URG11 in human NSCLC. Our results found that URG11 was highly expressed in human NSCLC tissues compared with matched normal lung tissues, and higher levels were found in NSCLC cell lines in comparison to the normal lung cell line. Moreover, we also found that knockdown of URG11 significantly inhibited proliferation, migration/invasion of NSCLC cells, as well as suppressed tumor growth in vivo. Furthermore, knockdown of URG11 suppressed the expression of ß-catenin, c-Myc, and cyclin D1 in NSCLC cells. Taken together, the study reported here provided evidence that URG11 downregulation suppresses proliferation, invasion, and ß-catenin expression in NSCLC cells. Thus, URG11 may be a novel potential therapeutic target for NSCLC.

Comparison of the metabolic profiling of hepatitis B virus-infected cirrhosis and alcoholic cirrhosis patients by using (1) H NMR-based metabonomics.

AIM: The aims of the present study were to depict the serum metabolic characteristics of hepatitis B virus (HBV)-infected cirrhosis and alcoholic cirrhosis patients, and to find the specific serum biomarkers associated with the diseases. METHODS: A pilot metabolic profiling study was conducted using three groups: HBV-infected cirrhosis patients (n = 21), alcoholic cirrhosis patients (n = 20) and healthy controls (n = 20). (1) H nuclear magnetic resonance (NMR)-based metabonomics was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The discriminatory metabolites between HBV-infected cirrhosis and alcoholic cirrhosis were further validated by classical biochemical assays. RESULTS: The OPLS-DA model was capable of distinguishing between HBV-infected and alcoholic cirrhosis patients. Five metabolites, creatine, acetoacetate, isobutyrate, glutamine and glutamate, were identified as the most influential factors to compare HBV-infected cirrhosis and alcoholic cirrhosis. The validation tests showed that the changes of the five metabolites were well coincident with the results of NMR. CONCLUSION: NMR spectra combined with pattern recognition analysis techniques may provide a new way to explore the pathogenesis of HBV-infected and alcoholic cirrhosis patients.

¹H NMR-based serum metabolic profiling in compensated and decompensated cirrhosis.

AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A ¹H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R²Y of 0.784 and a Q²Y of 0.598. Twelve metabolites, such as pyruvate, phenylalanine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: ¹H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.

CpG array analysis of histone H3 lysine 4 trimethylation in peripheral blood mononuclear cells of uremia patients.

Studies of the epigenome have attracted little interest in nephrology, especially in uremia. Several lines of evidence have suggested that there are links between genomic DNA hypomethylation and cardiovascular complications in uremia patients. However, to date, our knowledge about the alterations in histone methylation in uremia is unknown. H3K4me3 variations were analyzed in peripheral blood mononuclear cells from 20 uremia patients and 20 healthy subjects, using chromatin immunoprecipitation microarray (ChIP-chip) approach. ChIP-real-time polymerase chain reaction (PCR) was used to validate the microarray results. mRNA expression and DNA methylation status can be further analyzed by quantitative (q) reverse transcription (RT)-PCR and methyl-DNA immunoprecipitation (MeDIP)-qPCR, respectively. Seven hundred twenty-six increased and 218 decreased H3K4me3 genes displaying significant H3K4me3 differences were found in uremia patients compared with healthy subjects. The results of ChIP-real-time PCR coincided well with microarray results. Expression analysis by qRT-PCR revealed positive correlations between mRNA and H3K4me3 levels. Aberrant DNA methylation can also be found on selected positive genes (CNOT1 PLTP EDG1 TCF3 KIR3DL2). In addition, we even found that there is an inverse relationship between H3K4me3 and promoter DNA methylation in uremia patients. Our studies indicate that there are significant alterations of H3K4me3 in uremia patients; these significant H3K4me3 candidates may help to explain the immunological disturbance and high cardiovascular complications in uremia patients. Such novel findings show the significance of H3K4me3 as a potential biomarker or promising target for epigenetic-based uremia therapies.

Genome-wide analysis of histone H3 lysine 4 trimethylation in peripheral blood mononuclear cells of minimal change nephrotic syndrome patients.

BACKGROUND: Studies of the epigenome have attracted some interest in nephrology. However, to date, our knowledge about the alterations in histone modification in minimal change nephrotic syndrome (MCNS) is unknown. This study aimed to investigate the variations in histone H3 lysine 4 trimethylation (H3K4me3) in peripheral blood mononuclear cells of patients with MCNS. METHODS: H3K4me3 variations were analyzed in peripheral blood mononuclear cells, from 15 MCNS patients and 15 healthy subjects, using the ChIP-chip approach. ChIP real-time PCR is used to validate the microarray results. In addition, mRNA expression and DNA methylation status can also be further analyzed by quantitative (q) RT-PCR and methyl-DNA immunoprecipitation-q PCR, respectively. RESULTS: 848 increased and 231 decreased H3K4me3 probes displaying significant H3K4me3 differences were found in MCNS patients compared with healthy subjects. The results of ChIP real-time PCR coincided well with the microarray. Expression analysis by qRT-PCR revealed positive correlations between mRNA and H3K4me3 levels. DNA methylation alterations were found on selected positive genes (IL4R, HIVEP3, HPSE2, CDH13 and PRKD2). In addition, we also found that there is an inverse relationship between H3K4me3 and promoter DNA methylation in MCNS patients. CONCLUSION: Our studies indicate that there are significant alterations of H3K4me3 in MCNS patients. These significant H3K4me3 candidates may help to explain the immunological disturbance involved in MCNS patients.

[Boost effect of recombinant IL-4 on protection of Schistosoma japonicum cathepsin B DNA vaccine in mice against the parasite].

OBJECTIVE: To investigate the enhancement effect of IL-4 expression plasmid on cathepsin B DNA vaccine of Schistosoma japonicum (Sj) in mice. METHODS: The recombinant IL-4 plasmid constructed by cloning PCR amplified product of murine IL-4 gene into eukaryotic expression vector pcDNA3.1 was co-injected intramuscularly with Sj cathepsin B expression plasmid DNA to mice as the test group. The other three groups of mice were set up as control including IL-4 expression plasmid, Sj cathepsin B expression plasmid and two vacant vector plasmids. The expression of IL-4 and cathepsin B was visualized by immunohistochemistry. Challenge infection in mice was carried out 3 weeks after the last vaccination and immune protection was assessed by worm and egg reduction rates. RESULTS: The recombinant mIL-4 plasmid and cathepsin B DNA vaccine were expressed in muscular cells of the vaccinated mice. Immunization with cathepsin B DNA plus recombinant mIL-4 plasmid yielded a 43.2 % of worm reduction rate and a 76.6% of egg reduction rate, showing a significant difference (P<0.01, P<0.05) compared with that of cathepsin B DNA vaccine alone. CONCLUSION: As an adjuvant, IL-4 DNA can improve the protective effect of cathepsin B DNA vaccine in mice against S. japonicum infection.