Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Integrated assessment of environmental and economic impact of municipal solid waste incineration for power generation: A case study in China.

Municipal solid waste incineration for power generation is significant for reducing and reusing solid waste. The study conducted an integrated assessment of environment and economy on municipal solid waste incineration in China, from a "cradle to grave" perspective using 1 tonne of municipal solid waste incineration as the functional unit. The environmental impacts of each month are also calculated to analyze the dynamic change throughout one year. The results indicate that the environmental impacts are mainly concentrated in marine ecotoxicity, freshwater ecotoxicity, human carcinogenic toxicity, and human non-carcinogenic toxicity. Flue gas purification, waste incineration and transportation are the key processes, which account for 65.61 %, 18.50 %, and 11.93 % of the overall environmental impact, respectively. Urea, activated carbon, chelating agent (EDTA) and diesel fuel for transportation are key factors. The life cycle cost (LCC) is 132.26 RMB/t of waste, of which the initial capital causes the largest economic cost. When considering power generated from municipal solid waste incineration to replace electricity supply from the power grid, it achieves significant environmental benefits and the normalized environmental impact value changes from 0.85 to -12.19. The findings provide references for municipal solid waste treatment to mitigate the environmental impact and reduce the economic burden across the entire life cycle.

Cystathionine γ-lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia.

BACKGROUND: Diabetes is one of the major inflammatory comorbidities of periodontitis via 2-way interactions. Cystathionine γ-lyase (CTH) is a pivotal endogenous enzyme synthesizing hydrogen sulfide (H2S), and CTH/H2S is crucially implicated in modulating inflammation in various diseases. This study aimed to explore the potential role of CTH in experimental periodontitis under a hyperglycemic condition. METHODS: CTH-silenced and normal human periodontal ligament cells (hPDLCs) were cultured in a high glucose and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both Cth-/- and wild-type (WT) mice, and the extent of periodontal destruction was assessed by micro-CT, histology, RNA-Seq, Western blot, tartrate-resistant acid phosphatase (TRAP) staining and immunostaining. RESULTS: CTH mRNA expression increased in hPDLCs in response to increasing concentration of P.g-LPS stimulation in a high glucose medium. With reference to WT mice, Cth-/- mice with experimental periodontitis under hyperglycemia exhibited reduced bone loss, decreased leukocyte infiltration and hindered osteoclast formation, along with reduced expression of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in periodontal tissue. RNA-seq-enriched altered NF-κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P-p65) was alleviated in CTH-silenced hPDLCs, leading to decreased expression of IL6 and TNF. CTH knockdown inhibited activation of nuclear factor kappa-B (NF-κB) pathway and decreased production of proinflammatory cytokines under high glucose and P.g-LPS treatment. CONCLUSION: The present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.

A prospective study on maternal periodontal diseases and neonatal adverse outcomes.

OBJECTIVE: It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. MATERIALS AND METHODS: A total of 193 generally healthy females in their third trimester (34-36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA.  Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. CONCLUSION: Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Proteome-Wide Mendelian Randomisation Identifies Causal Links of Plasma Proteins With Periodontitis.

OBJECTIVE: Periodontitis is a complex and multifactorial disease and it is challenging to decipher its underlying causes and mechanisms. This study attempted to explore potential circulating proteins in connection to periodontitis through proteome-wide Mendelian randomisation (MR). METHODS: We analysed 1722 circulating proteins to identify prospective drug targets for tackling periodontitis, using the genomic dataset from the FinnGen study. Two-sample MR was conducted to evaluate the bidirectional relationship between circulating proteins and periodontitis risk. A dataset from the UK Biobank was used to validate the findings. Single-cell analysis was performed to assess the cellular expression of the identified proteins within gingival tissues. RESULTS: MR analyses found that genetically predicted circulating levels of von Willebrand factor A domain-containing 1 (von Willebrand factor A domain containing 1 [VWA1], odds ratios: 0.94, 95% CI 0.92-0.97, P = 1.28 × 10-5) were inversely associated with periodontitis. In contrast, the level of growth differentiation factor 15 (growth differentiation factor 15 [GDF15], odds ratios: 1.05, 95% CI 1.02-1.07, P = 2.12 × 10-5) might be associated with an increased risk of periodontitis. Single-cell analysis indicated that VWA1 was primarily expressed in endothelial cells of healthy gingival tissues, while the main source of GDF15 was not derived from periodontal cells. CONCLUSIONS: The present study suggests that certain plasma proteins like VWA1 and GDF15 may be potentially indicative of the risk and susceptibility to periodontitis. These proteins could possibly be the potential therapeutic targets for treating periodontitis, and further investigation is highly warranted.

Integration of metalloproteome and immunoproteome reveals a tight link of iron-related proteins with COVID-19 pathogenesis and immunity.

Increasing clinical data show that the imbalance of host metallome is closely associated with different kinds of disease, however, the intrinsic mechanisms of action of metals in immunity and pathogenesis of disease remain largely undefined. There is lack of multiplexed profiling system to integrate the metalloproteome-immunoproteome information at systemic level for exploring the roles of metals in immunity and disease pathogenesis. In this study, we build up a metal-coding assisted multiplexed proteome assay platform for serum metalloproteomic and immunoproteomic profiling. By taking COVID-19 as a showcase, we unbiasedly uncovered the most evident modulation of iron-related proteins, i.e., Ft and Tf, in serum of severe COVID-19 patients, and the value of Ft/Tf could work as a robust biomarker for COVID-19 severity stratification, which overtakes the well-established clinical risk factors (cytokines). We further uncovered a tight association of transferrin with inflammation mediator IL-10 in COVID-19 patients, which was proved to be mainly governed by the monocyte/macrophage of liver, shedding light on new pathophysiological and immune regulatory mechanisms of COVID-19 disease. We finally validated the beneficial effects of iron chelators as anti-viral agents in SARS-CoV-2-infected K18-hACE2 mice through modulation of iron dyshomeostasis and alleviating inflammation response. Our findings highlight the critical role of liver-mediated iron dysregulation in COVID-19 disease severity, providing solid evidence on the involvement of iron-related proteins in COVID-19 pathophysiology and immunity.

Efficacy of Alveolar Ridge Preservation in Periodontally Compromised Molar Extraction Sites: A Systematic Review and Meta-Analysis.

AIM: To investigate the efficacy of alveolar ridge preservation (ARP) in periodontally compromised molar extraction sites. METHODS: An electronic search was performed on 10th November 2023 across five databases, seeking randomised/non-randomised controlled trials (RCTs/NCTs) that included a minimum follow-up duration of four months. The RoB2 and Robins-I tools assessed the risk of bias for the included studies. Data on alveolar ridge dimensional and volumetric changes, keratinized mucosal width, and need for additional bone augmentation for implant placement were collected. Subsequently, a meta-analysis was carried out to derive the pooled estimates. RESULTS: Six studies were incorporated in the present review, and a total of 135 molar extraction sockets in 130 subjects were included in the meta-analysis. ARP was undertaken in 68 sites, and 67 sites healed spontaneously. The follow-up time ranged from 4 to 6 months. The meta-analysis of both RCTs and NCTs showed significant differences in mid-buccal ridge width changes at 1 mm level below ridge crest with a mean difference (MD) of 3.80 (95% CI: 1.67-5.94), mid-buccal ridge height changes (MD: 2.18; 95% CI: 1.25-3.12) and volumetric changes (MD: 263.59; 95% CI: 138.44-388.74) in favour of ARP, while the certainty of evidence is graded low to very low. Moreover, ARP appeared to reduce the need for additional sinus and bone augmentation procedures at implant placement with low certainty of evidence. CONCLUSIONS: Within the limitations of this study, alveolar ridge preservation in periodontally compromised extraction sites may, to some extent, preserve the ridge vertically and horizontally with reference to spontaneous healing. However, it could not eliminate the need for additional augmentation for implant placement. Further, longitudinal studies with large sample sizes and refined protocols are needed.

Learn, unlearn, and relearn post-extraction alveolar socket healing: Evolving knowledge and practices.

OBJECTIVE: This review was to offer a comprehensive analysis of currently available evidence on post-extraction alveolar socket healing, including i) the histological and molecular events during alveolar socket healing, ii) the dimensional ridge alterations after socket healing and controversies relating to sinus pneumatisation, iii) the patient-specific factors, procedural elements, and site-related variables influencing socket healing, iv) techniques and effectiveness of alveolar ridge preservation (ARP) procedure, and v) the philosophies and cost-effectiveness of ARP in clinical practice. SOURCES AND STUDY SELECTION: To investigate the dimensional profiles of the alveolar ridge following unassisted healing, an overview of systematic reviews was conducted in February 2024 by two independent reviewers. Four electronic databases were searched in Pubmed, Embase, Web of science and Cochrane Library between 2004 and 2024 to identify all relevant systematic reviews on post-extraction healing. A further manual search of reviews was also conducted. The articles were further reviewed in full text for relevance. The AMSTAR-2 appraisal tool was adopted to assess methodological quality. Current research pertaining to other listed objectives was objectively analysed in narration. DATA: 11 out of 459 retrieved studies were selected and ultimately covered in this review on the dimensional changes of alveolar ridge following natural healing: Seven systematic reviews and four systematic reviews with meta-analyses. The methodological quality of all included reviews was critically low. CONCLUSION: This review thoroughly examines the healing profiles of post-extraction alveolar sockets and highlights the dynamic process with overlapping phases and the inter-individual variability in outcomes. ARP procedure is a potential strategy for facilitating prosthetic site development, while the current evidence is limited. Herein, an individualised and prosthetically driven approach is crucial. Further well sized and designed trials with novel biomaterials need to be undertaken, and the role of artificial intelligence in predicting healing and assisting clinical decision-making could be explored. CLINICAL SIGNIFICANCE: By advancing our understanding of alveolar socket healing and its management strategies, clinicians can make more informed decisions regarding patient and site level assessment and selection, surgical techniques, and biomaterial choices, ultimately contributing to the enhanced healing process with reduced complications and improved quality of life for patients undergoing tooth extraction and dental implant treatments.

Motivational Interviewing on Periodontal Treatment Outcomes: A Meta-Analysis.

OBJECTIVES: This systematic review investigated the clinical efficacy of motivational interviewing (MI) in improving oral hygiene and periodontal health in patients with periodontal diseases. METHODS: A comprehensive literature search was conducted across various databases up to May 2023. Randomised controlled trials (RCTs) evaluating the effects of MI on periodontal conditions in patients with gingivitis, periodontitis, and peri­implantitis were included. After data screening, a risk-of-bias assessment was performed using the Cochrane risk of bias (RoB) tool. The meta-analysis was performed using random-effects models. RESULTS: Out of 2108 records screened, 7 RCTs involving 474 patients were included in the qualitative synthesis, with 6 of these studies included in the meta-analysis. Amongst these, 5 studies had a high RoB and 2 had some concerns about bias. Although individual studies reported varied results regarding the effects of MI on different periodontal indices and parameters at different time points, the pooled results revealed no significant difference in the overall effect on plaque level, bleeding on probing, and gingival inflammation between the MI and control groups. In addition, there is insufficient evidence to suggest any significant effect on attachment loss or probing depth. CONCLUSIONS: The current evidence is insufficient to support the effectiveness of MI as an adjunctive intervention for improving oral hygiene and periodontal outcomes. However, these results should be interpreted with caution. Additional high-quality studies with standardised MI interventions are required to derive definite conclusions.

Phase Change Study of a New Two-Phase Absorbent Based on DAP.

In order to overcome the drawbacks of conventional absorbents, which exhibit slow absorption rates and low absorption loads, this study suggests enhancing the absorbent system for CO2 absorption by incorporating a nonaqueous solvent into 1,3-propanediamine (DAP) and tetramethylethylenediamine (TMEDA), resulting in a two-phase system. The mechanism of solvent absorption of CO2 was investigated using nuclear magnetic resonance (NMR) carbon spectroscopy. By comparing the absorption load, fraction ratio, and viscosity of different absorbents after absorbing carbon dioxide, the two-phase absorbents with good performance were selected. The poor water absorbent consisting of the DAP/TMEDA system exhibited an absorption load of 3.8 mol/kg, surpassing that of the conventional 30% ethanolamine solution. A nonaqueous solvent is added to the system to replace some of the water to reduce the fraction. After adding different nonaqueous solvents, the phase separation system was screened after 2 h of CO2 absorption. The system with good performance was tested for the absorption of the solution under different amine concentration and water concentration tests. It is found that the absorption load of the DAP/TMEDA/diglyme system is 3.2 mol/kg, but the fraction can be reduced to 38%. The significant reduction in rich phase volume is beneficial for reducing the size and cost of regeneration tower. According to NMR detection and quantum chemical calculations, it was found that DAP/TMEDA absorbs carbon dioxide to form carbamate. DAP acts as the main absorbent, while TMEDA and nonaqueous solvents do not participate in the absorption reaction. Nonaqueous solvents were found to accelerate the solution phase separation due to the salt precipitation reaction.

Metal-coding assisted serological multi-omics profiling deciphers the role of selenium in COVID-19 immunity.

Uncovering how host metal(loid)s mediate the immune response against invading pathogens is critical for better understanding the pathogenesis mechanism of infectious disease. Clinical data show that imbalance of host metal(loid)s is closely associated with the severity and mortality of COVID-19. However, it remains elusive how metal(loid)s, which are essential elements for all forms of life and closely associated with multiple diseases if dysregulated, are involved in COVID-19 pathophysiology and immunopathology. Herein, we built up a metal-coding assisted multiplexed serological metallome and immunoproteome profiling system to characterize the links of metallome with COVID-19 pathogenesis and immunity. We found distinct metallome features in COVID-19 patients compared with non-infected control subjects, which may serve as a biomarker for disease diagnosis. Moreover, we generated the first correlation network between the host metallome and immunity mediators, and unbiasedly uncovered a strong association of selenium with interleukin-10 (IL-10). Supplementation of selenium to immune cells resulted in enhanced IL-10 expression in B cells and reduced induction of proinflammatory cytokines in B and CD4+ T cells. The selenium-enhanced IL-10 production in B cells was confirmed to be attributable to the activation of ERK and Akt pathways. We further validated our cellular data in SARS-CoV-2-infected K18-hACE2 mice, and found that selenium supplementation alleviated SARS-CoV-2-induced lung damage characterized by decreased alveolar inflammatory infiltrates through restoration of virus-repressed selenoproteins to alleviate oxidative stress. Our approach can be readily extended to other diseases to understand how the host defends against invading pathogens through regulation of metallome.

Comparative analysis of serum and saliva samples using Raman spectroscopy: a high-throughput investigation in patients with polycystic ovary syndrome and periodontitis.

BACKGROUND: Polycystic ovary syndrome (PCOS) and periodontitis significantly affect women's oral and systemic health worldwide, and yet increase the risk of cardiovascular-metabolic diseases like diabetes and coronary heart disease. Regarding the PCOS-periodontitis connection, whether sex hormones, metabolic and inflammatory mediators could account for the underlying linking mechanism needs to be further investigated. This case-control study evaluated the hormonal, metabolic and inflammatory profiles in PCOS and non-PCOS subjects with various periodontal conditions, via assessing serum and saliva samples by Raman spectroscopy. METHODS: A total of 66 females with PCOS and 22 systemically healthy female volunteers were recruited in a single hospital. Full-mouth periodontal examination was undertaken for identifying the subjects with periodontal health, gingivitis or periodontitis. The datasets of sex hormones and metabolic indicators were retrieved from the hospital information system. Both serum and saliva samples were collected for detecting inflammatory mediators and Raman spectroscopic assessment. The subjects were categorized into four groups according to their conditions of PCOS and periodontitis for Raman spectroscopic analysis. Partial least squares discriminant analysis was performed to examine the inter-group differences in Raman spectra. RESULTS: PCOS patients exhibited greater mean probing depth (P < 0.05) and higher serum levels of triglycerides (P < 0.05) and matrix metalloproteinase-8 (P < 0.05) than those in non-PCOS participants. Both probing depth and triglyceride level were positively correlated with PCOS (P < 0.05). There was a significant difference in mean Raman spectra of saliva samples among the four groups with different conditions of PCOS and periodontitis (P < 0.05), while no significant inter-group difference existed in serum samples. CONCLUSIONS: The present study shows that periodontal condition may affect the biomolecular profiles of Raman spectra in serum and saliva of PCOS patients. It underscores the importance of the collaborative teamwork of dentists and gynecologists for enhancing women's oral health, general wellbeing and quality of life.

Maternal periodontal diseases affect the leukocyte profiles of umbilical cord blood: A cohort study.

AIM: This study evaluated the connection of periodontal status with the leukocyte profiles of maternal peripheral blood (MPB) and umbilical cord blood (UCB). MATERIALS AND METHODS: Ninety-nine pregnant females were recruited, and their data were collected via questionnaire and from medical records, including demographics, systemic conditions, complete blood count (CBC) and C-reaction protein (CRP) level in MPB. Full-mouth periodontal assessment was performed. CBC and CRP levels in UCB were measured after parturition. RESULTS: All subjects and their neonates were generally healthy. 30.3% of the participants presented with periodontal health condition, whereas 69.7% had different severities of periodontal diseases. The counts/percentages of eosinophils and monocytes in UCB from the subjects with periodontal diseases elevated, and the percentage of neutrophils decreased referencing to that from the counterparts (p < 0.05). There were positive correlations for total leukocyte count, neutrophils and lymphocytes counts/percentages in MPB and UCB among the periodontally healthy subjects (r > 0.4, p < 0.05), but such findings did not exist in those with periodontal diseases. Moreover, periodontal diseases independently accounted for the counts/percentages of neutrophils and eosinophils in UCB after controlling confounders in four testing models (ANCOVA, p < 0.05). CONCLUSION: Maternal periodontal diseases could to some extent disturb the leukocyte profiles of umbilical cord blood.

Effects of Low-Level Laser Therapy on Dentin Hypersensitivity in Periodontally Compromised Patients Undergoing Orthodontic Treatment: A Randomised Controlled Trial.

OBJECTIVES: This study aimed to assess the effects of low-level laser therapy (LLLT) on dentin hypersensitivity (DH) in periodontally compromised patients undergoing orthodontic treatment. METHODS: This triple-blinded randomised controlled trial included 143 teeth with DH from 23 periodontally compromised patients. Teeth on one side of the dental arch were randomly assigned to the LLLT group (LG), while those on the contralateral side were allocated to the non-LLLT group (NG). After orthodontic treatment commenced, patients' orthodontic pain (OP) perceptions were documented in pain diaries. DH was assessed chairside by a visual analogue scale (VASDH) at fifteen timepoints across the orthodontic treatment and retention. VASDH scores were compared among timepoints by the Friedman test, among patients with varying OP perceptions using the Kruskal-Wallis tests, and between the LG and NG with the Mann-Whitney U test. RESULTS: DH generally decreased over the observation (p < 0.001). The VASDH scores differed among patients with varying OP perceptions at multiple timepoints (p < 0.05). The generalized estimating equation model showed teeth in the LG had a significantly lower VASDH score than the NG at the 3rd month of treatment (p = 0.011). CONCLUSION: LLLT could be potentially beneficial in managing DH in periodontally compromised patients undergoing orthodontic treatment.

Microbial persisters and host: recent advances and future perspectives.

Microbial persisters are defined as the tiny sub-population of microorganisms that develop intrinsic strategies for survival with high tolerance to various antimicrobials. Currently, persister research remains in its infancy, and it is indeed a great challenge to precisely distinguish persister cells from other drug tolerant ones. Notably, the existence of persisters crucially contributes to prolonged antibiotic exposure time and treatment failure, yet there is the formation of antibiotic-resistant mutants. Further understanding on persisters is of profound importance for effective prevention and control of chronic infections/inflammation. The past two decades have witnessed rapid advances on the science, technologies and methodologies for persister investigations, along with deep knowledge about persisters and numerous anti-persister approaches developed. Whereas, various critical issues remain unsolved, such as what are the potential interaction profiles of persisters and host cells, and how to apply what we know about persisters to translational studies and clinical practice. Importantly, it is highly essential to better understand the multifaceted and complex cross-talk of microbial persisters with the host to develop novel tackling strategies for precision healthcare in the near future.

Periodontal ligament cells from patients with treated stable periodontitis: Characterization and osteogenic differentiation potential.

BACKGROUND AND OBJECTIVE: Periodontal ligament progenitor cells (PDL cells) isolated from patients with inflammatory periodontitis have impaired regenerative capacity, but it is unknown whether this capacity can be recovered upon treatment and stabilization of the periodontal condition. The study aimed to investigate the expression of surface markers and the proliferation and osteogenic potential of PDL cells isolated from patients with treated stable periodontitis (S-PDL cells), periodontally healthy individuals (H-PDL cells), and patients with inflammatory periodontitis (I-PDL cells). METHODS: H-PDL, I-PDL, and S-PDL cells were isolated from the extracted teeth of individuals who (1) were periodontally healthy, (2) had inflammatory periodontitis, and (3) had treated stable periodontitis, respectively. The expression levels of surface markers and the proliferative and osteogenic capacities of the PDL cells were assessed. RESULTS: PDL cells derived from all three sources exhibited mesenchymal stem cell (MSC) characteristics. They were positive for MSC-related markers and negative for a hematopoiesis-related marker. However, S-PDL cells had higher proliferation rates, higher expression levels of osteogenic markers, higher alkaline phosphatase activity, and more calcium nodules than I-PDL cells. But all of these parameters remained lower in S-PDL cells than in H-PDL cells. CONCLUSIONS: S-PDL cells proliferated faster and had greater osteogenic potential than I-PDL cells, although these values remained lower than those in H-PDL cells.

Rapid synthesis of bismuth-organic frameworks as selective antimicrobial materials against microbial biofilms.

Antibiotic resistance is a global public health threat, and urgent actions should be undertaken for developing alternative antimicrobial strategies and approaches. Notably, bismuth drugs exhibit potent antimicrobial effects on various pathogens and promising efficacy in tackling SARS-CoV-2 and related infections. As such, bismuth-based materials could precisely combat pathogenic bacteria and effectively treat the resultant infections and inflammatory diseases through a controlled release of Bi ions for targeted drug delivery. Currently, it is a great challenge to rapidly and massively manufacture bismuth-based particles, and yet there are no reports on effectively constructing such porous antimicrobial-loaded particles. Herein, we have developed two rapid approaches (i.e., ultrasound-assisted and agitation-free methods) to synthesizing bismuth-based materials with ellipsoid- (Ellipsoids) and rod-like (Rods) morphologies respectively, and fully characterized physicochemical properties. Rods with a porous structure were confirmed as bismuth metal-organic frameworks (Bi-MOF) and aligned with the crystalline structure of CAU-17. Importantly, the formation of Rods was a 'two-step' crystallization process of growing almond-flake-like units followed by stacking into the rod-like structure. The size of Bi-MOF was precisely controlled from micro-to nano-scales by varying concentrations of metal ions and their ratio to the ligand. Moreover, both Ellipsoids and Rods showed excellent biocompatibility with human gingival fibroblasts and potent antimicrobial effects on the Gram-negative oral pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Both Ellipsoids and Rods at 50 â€‹µg/mL could disrupt the bacterial membranes, and particularly eliminate P. gingivalis biofilms. This study demonstrates highly efficient and facile approaches to synthesizing bismuth-based particles. Our work could enrich the administration modalities of metallic drugs for promising antibiotic-free healthcare.

A Multimodal Deep Learning Approach to Predicting Systemic Diseases from Oral Conditions.

Background: It is known that oral diseases such as periodontal (gum) disease are closely linked to various systemic diseases and disorders. Deep learning advances have the potential to make major contributions to healthcare, particularly in the domains that rely on medical imaging. Incorporating non-imaging information based on clinical and laboratory data may allow clinicians to make more comprehensive and accurate decisions. Methods: Here, we developed a multimodal deep learning method to predict systemic diseases and disorders from oral health conditions. A dual-loss autoencoder was used in the first phase to extract periodontal disease-related features from 1188 panoramic radiographs. Then, in the second phase, we fused the image features with the demographic data and clinical information taken from electronic health records (EHR) to predict systemic diseases. We used receiver operation characteristics (ROC) and accuracy to evaluate our model. The model was further validated by an unseen test dataset. Findings: According to our findings, the top three most accurately predicted chapters, in order, are the Chapters III, VI and IX. The results indicated that the proposed model could predict systemic diseases belonging to Chapters III, VI and IX, with AUC values of 0.92 (95% CI, 0.90-94), 0.87 (95% CI, 0.84-89) and 0.78 (95% CI, 0.75-81), respectively. To assess the robustness of the models, we performed the evaluation on the unseen test dataset for these chapters and the results showed an accuracy of 0.88, 0.82 and 0.72 for Chapters III, VI and IX, respectively. Interpretation: The present study shows that the combination of panoramic radiograph and clinical oral features could be considered to train a fusion deep learning model for predicting systemic diseases and disorders.

N6-methyladenosine of Socs1 modulates macrophage inflammatory response in different stiffness environments.

Macrophages exhibit diverse functions within various tissues during the inflammatory response, and the physical properties of tissues also modulate the characteristics of macrophages. However, the underlying N6-methyladenosine (m6A)-associated molecular mechanisms remain unclear. Accordingly, we examined the potential role of m6A in macrophage activation and stiffness sensing. Intriguingly, we found that the macrophage inflammatory response and global levels of m6A were stiffness-dependent and that this was due to mechanically loosening the chromatin and epigenetic modification (H3K36me2 and HDAC3). In addition, we targeted suppressor of cytokine signalling 1 (Socs1) m6A methylation in a stiffness-dependent manner by screening the sequencing data and found that a higher stiffness hydrogel activated Jak-STAT and NFκB signalling and suppressed Fto gene expression. Next, by using the CRISPR/Cas9 system to knockout the FTO gene in macrophages, we demonstrated that FTO affects the stiffness-controlled macrophage inflammatory response by sustaining the negative feedback generated by SOCS1. Finally, we determined that the m6A reader YTHDF1 binds Socs1 mRNA and thereby maintains expression of SOCS1. Our results suggest that the FTO/Socs1/YTHDF1 regulatory axis is vital to the stiffness-controlled macrophage inflammatory response and that the deletion of FTO affects the negative feedback control exerted by SOCS1. Our findings increase understanding of the regulatory mechanisms involved in macrophage activation and the control of inflammation.

Mendelian randomization supports the causal role of fasting glucose on periodontitis.

Purpose: The effect of hyperglycemia on periodontitis is mainly based on observational studies, and inconsistent results were found whether periodontal treatment favors glycemic control. The two-way relationship between periodontitis and hyperglycemia needs to be further elucidated. This study aims to evaluate the causal association of periodontitis with glycemic traits using bi-directional Mendelian randomization (MR) approach. Methods: Summary statistics were sourced from large-scale genome-wide association study conducted for fasting glucose (N = 133,010), HbA1c (N = 123,665), type 2 diabetes (T2D, N = 659,316), and periodontitis (N = 506,594) among European ancestry. The causal relationship was estimated using the inverse-variance weighted (IVW) model and further validated through extensive complementary and sensitivity analyses. Results: Overall, IVW showed that a genetically higher level of fasting glucose was significantly associated with periodontitis (OR = 1.119; 95% CI = 1.045-1.197; PFDR= 0.007) after removing the outlying instruments. Such association was robust and consistent through other MR models. Limited evidence was found suggesting the association of HbA1C with periodontitis after excluding the outliers (IVW OR = 1.123; 95% CI = 1.026-1.229; PFDR= 0.048). These linkages remained statistically significant in multivariate MR analyses, after adjusting for body mass index. The reverse direction MR analyses did not exhibit the causal association of genetic liability to periodontitis with any of the glycemic trait tested. Conclusions: Our MR study reaffirms previous findings and extends evidence to substantiate the causal effect of hyperglycemia on periodontitis. Future studies with robust genetic instruments are needed to confirm the causal association of periodontitis with glycemic traits.