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Purpose: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. Materials and Methods: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). Results: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). Conclusions: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimers disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.

Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer's disease (AD), remain unclear. This study assessed the effects of Pg's virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels. In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders. • Periodontitis represents a causal risk factor for multiple systemic diseases, including neurodegenerative disorders. • Lipopolysaccharide and gingipains from Porphyromonas gingivalis elicited toxic effects in human SH-SY5Y neuroblastoma cells. • Preventing GRK5 downregulation is a potential strategy to abolish Pg-dependent harmful effects induced in human SH-SY5Y neuroblastoma cells. [ABSTRACT FROM AUTHOR]

Objective: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). Design: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. Results: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). Conclusions: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a gram‐negative anaerobic bacterium recognized for its pivotal role in the pathogenesis of periodontal diseases. This review covers an overview of the virulence factors and lifecycle stages of P. gingivalis, with a specific focus on attachment and colonization, biofilm formation, growth and multiplication, dormancy survival and dissemination. Additionally, we explore the significance of inter‐bacterial cross‐feeding within biofilms. Furthermore, we discuss potential phytochemical‐based strategies to target P. gingivalis, including the use of curcumin, apigenin, quercetin and resveratrol. Understanding the virulence factors and lifecycle stages of P. gingivalis, along with the promising phytochemical‐based interventions, holds promise for advancing strategies in periodontal disease management and oral health promotion. [ABSTRACT FROM AUTHOR]

This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti‐inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g‐LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs‐induced osteoclast formation was assessed by treating human bone marrow‐derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate‐resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1, and IL‐18) at both gene and protein levels in hPLFs induced by P.g‐LPS. Furthermore, conditioned medium from Rb3 plus P.g‐LPS treated hPLFs notably decreased the number of TRAP‐positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g‐LPS‐induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g‐LPS‐stimulated hPLFs and reduces hPLFs‐induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis. Highlights: Ginsenoside Rb3 reduces inflammation in human periodontal ligament fibroblasts in a periodontitis microenvironment.Ginsenoside Rb3 inhibits the formation of osteoclasts mediated by human periodontal ligament fibroblasts.The effect of Ginsenoside Rb3 on the inflammation of human periodontal ligament fibroblasts and osteoclast formation is related to the inhibition of the STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background Materials and Methods Results Conclusions The PG1037 gene is part of the uvrA‐PG1037‐pcrA operon in Porphyromonas gingivalis. It encodes for a protein of unknown function upregulated under hydrogen peroxide (H2O2)‐induced oxidative stress. Bioinformatic analysis shows that PG1037 has a zinc‐finger motif, two peroxidase motifs, and one cytidylate kinase domain. The aim of this study is to characterize further the role of the PG1037 recombinant protein in the unique 8‐oxoG repair system in P. gingivalis.PG1037 recombinant proteins with deletions in the zinc‐finger or peroxidase motifs were created. Electrophoretic mobility shift assays were used to evaluate the ability of the recombinant proteins to bind 8‐oxoG‐containing oligonucleotides. Zinc binding, peroxidase, and Fenton reaction assays were used to assess the functional roles of the rPG1037 protein. A bacterial adenylate cyclase two‐bride assay was used to identify the partner protein of PG1037 in the repair of 8‐oxoG.The recombinant PG1037 (rPG1037) protein carrying an N‐terminal His‐tag demonstrated an ability to recognize and bind 8‐oxoG‐containing oligonucleotide. In contrast to the wild‐type rPG1037 protein, the zinc‐finger motif deletion resulted in the loss of zinc and 8‐oxoG binding activities. A deletion of the peroxidase motif‐1 showed a decrease in peroxidase activity. Using a bacterial adenylate cyclase two‐hybrid system, there was no observed protein‐protein interaction of PG1037 with UvrA (PG1036), PcrA (PG1038), or mismatch repair system proteins.Taken together, the results show that PG1037 is an important member of a novel mechanism that recognizes and repairs oxidative stress‐induced DNA damage in P. gingivalis. [ABSTRACT FROM AUTHOR]

Periodontal disease is more prevalent in patients with diabetes, and it has a negative impact on their quality of life. Inhibiting the infection and inflammation processes that cause periodontal disease can reduce the severity of the disease and chances of serious complications. In this study, we aimed to demonstrate the effectiveness of Clinacanthus nutans extract in reducing the inflammation in gingival fibroblast cells induced by Porphyromonas gingivalis lipopolysaccharide (LPS). Stimulation with LPS under high-glucose conditions led to increased inflammation compared to low-glucose conditions. Treatment of C. nutans extract significantly reduced the expression of these pro-inflammatory cytokines and chemokines. At a concentration of 50 μg/mL, it reduced the relative expression of IL6, IL8, and CXCL10 to 0.51 ± 0.09, 0.6 ± 0.19, and 0.09 ± 0.02, respectively, compared to the non-treatment control, accompanied by a decrease in secreted protein as measured by ELISA. Additionally, application of C. nutans extract markedly suppressed the NF-κB signaling pathway by reducing the phosphorylated form of IκBα, NF-κB p65, and nuclear translocation of NF-κB, along with a decrease in COX2, a key mediator in the inflammatory pathway. Furthermore, analysis of RNA sequencing data indicated that the extract clearly reversed the gene expression changes induced by LPS. This was particularly true for the signaling mediators and inflammatory genes in response to NF-κB, JAK/STAT, and TNF signaling pathways. Our finding highlights the potential of C. nutans extract to alleviate inflammation and suggests its potential as a treatment for periodontal disease in patients with diabetes. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis, a keystone oral pathogen implicated in development and progression of periodontitis, may also contribute to the pathogenicity of diseases such as arthritis, atherosclerosis, and Alzheimer's. P. gingivalis is a master manipulator of host immune responses due to production of a large variety of virulence factors. Among these, P. gingivalis peptidilarginine deiminase (PPAD), an enzyme unique to P. gingivalis, converts C-terminal Arg residues in bacterium- and host-derived proteins and peptides into citrulline. PPAD contributes to stimulation of proinflammatory responses in host cells and is essential for activation of the prostaglandin E2 (PGE2) synthesis pathway in gingival fibroblasts. Since P. gingivalis is recognized mainly by Toll-like receptor-2 (TLR2), we investigated the effects of PPAD activity on TLR2-dependent host cell responses to P. gingivalis, as well as to outer membrane vesicles (OMVs) and fimbriae produced by this organism. Using reporter cell lines, we found that PPAD activity was required for TLR2 activation by P. gingivalis cells and OMVs. We also found that fimbriae, an established TLR2 ligand, from wild-type ATCC 33277 (but not from its isogenic PPAD mutant) enhanced the proinflammatory responses of host cells. Furthermore, only fimbriae from wild-type ATCC 33277, but not from the PPAD-deficient strains, induced cytokine production and stimulated expression of genes within the PGE2 synthesis pathway in human gingival fibroblasts via activation of the NF-κB and MAP kinase-dependent signaling pathways. Analysis of ten clinical isolates revealed that type I FimA is preferable for TLR2 signaling enhancement. In conclusion, the data strongly suggest that both PPAD activity and fimbriae are important for TLR2-dependent cell responses to P. gingivalis infection. [ABSTRACT FROM AUTHOR]

Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment. [ABSTRACT FROM AUTHOR]

Background: Microorganisms colonizing the apical root canal system are conceivably the ones directly involved with the causation and maintenance of apical periodontitis. Objectives: This article systematically reviews the reports on the microbiome occurring exclusively at the apical root canal of teeth with primary and posttreatment apical periodontitis. Methods: The electronic databases PubMed, Embase, Web of Science, Science Direct, and Proquest were searched up to August 2023. Clinical studies using culture and molecular microbiology methods to identify the microbial taxa present exclusively in the apical root canal segment of infected teeth with apical periodontitis were included. Studies were critically assessed using the Joanna Briggs Institute Critical Prevalence Assessment Checklist. Results: From 2277 articles initially detected, 52 were selected for full reading and 21 were eventually included in this review. Of these, molecular methods were used in 19 and culture in 2 studies. Ten studies evaluated primary infections, 8 evaluated posttreatment infections, and 3 included both. Cryopulverization of the apical root specimens was conducted in 11 studies. All studies evaluated the prevalence and diversity of bacteria, and only one also reported on fungi. Overall, the most frequent/abundant bacterial taxa found in the apical canal of primary infections were Pseudoramibacter alactolyticus, Olsenella uli, Fusobacterium species, Streptococcus species, Porphyromonas endodontalis, Prevotella species, Actinomyces species, Parvimonas micra, Treponema denticola, Synergistetes species, and an as‐yet uncharacterized taxon. In posttreatment infections, the most prevalent/abundant bacterial taxa included species of Streptococcus, Enterococcus, Fusobacterium, Actinomyces, Pseudoramibacter, Pseudomonas, and Propionibacterium. At the phylum level, Firmicutes was the most represented. The average apical bacterial load ranged from 105 to 106 in primary infections and from 103 to 104 in posttreatment infections. Discussion: Microbial diversity in the apical part of the root canal system was examined encompassing data from both primary and posttreatment infections. Heterogeneity amongst the studies, especially in sample collection and microbial identification methods, is an important limitation that prevented a meta‐analysis. Conclusions: There is a pronounced bacterial diversity in the infected apical canal, with a high interindividual variability. Different microbiome compositions at the species/genus level are observed according to the infection type. Registration: PROSPERO CRD42021275886. [ABSTRACT FROM AUTHOR]

It has long been suggested that a bidirectional impact exists between periodontitis and diabetes. Periodontitis may affect diabetes glycemic control, insulin resistance, and diabetic complications. Diabetes can worsen periodontitis by delaying wound healing and increasing the chance of infection. Extracellular vesicles (EVs) are heterogeneous particles of membrane‐enclosed spherical structure secreted by eukaryotes and prokaryotes and play a key role in a variety of diseases. This review will introduce the biogenesis, release, and biological function of EVs from a microbial and host cell perspective, discuss the functional properties of EVs in the development of periodontitis and diabetes, and explore their role in the pathogenesis and clinical application of these two diseases. Their clinical implication and diagnostic value are also discussed. [ABSTRACT FROM AUTHOR]

One‐carbon metabolism (OCM) pathways are responsible for several functions, producing a number of one‐carbon unit intermediates (formyl, methylene, methenyl, methyl) that are required for the synthesis of various amino acids and other biomolecules such as purines, thymidylate, redox regulators, and, in most microbes, folate. As humans must acquire folate from the diet, folate production is a target for antimicrobials such as sulfonamides. OCM impacts the regulation of microbial virulence such that in a number of instances, limiting the availability of para‐aminobenzoic acid (pABA), an essential OCM precursor, causes a reduction in pathogenicity. Porphyromonas gingivalis, however, displays increased pathogenicity in response to lower pABA levels, and exogenous pABA exerts a calming influence on heterotypic communities of P. gingivalis with pABA‐producing partner species. Differential responses to pABA may reflect both the physiology of the organisms and their host microenvironment. OCM plays an integral role in regulating the global rate of protein translation, where the alarmones ZMP and ZTP sense insufficient stores of intracellular folate and coordinate adaptive responses to compensate and restore folate to sufficient levels. The emerging interconnections between OCM, protein synthesis, and context‐dependent pathogenicity provide novel insights into the dynamic host–microbe interface. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods A total of 180 C57BL/6 mice were randomly divided into 6 groups, i. e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01, 9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2 ), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68, 7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is the most pathogenic periodontal bacterium in the world. Recently, P. gingivalis has been considered responsible for dysbiosis during the development of periodontitis. This study aimed to evaluate a novel immunochromatographic device using monoclonal antibodies against P. gingivalis in subgingival plaques. A total of 72 patients with chronic periodontitis and 53 periodontally healthy volunteers underwent clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis and compared using real-time polymerase chain reaction (PCR). In the periodontitis group, a significant positive correlation was observed between the test device scores and the real-time PCR results. The specificity, positive predictive value, negative predictive value, and accuracy of the test device for P. gingivalis, as determined by real-time PCR, were 98%, 94%, 89%, and 90%, respectively. There were significant differences in bacterial counts by real-time PCR among the groups with different ranges of device scores. Additionally, there was a significant positive correlation between the device scores for P. gingivalis and periodontal parameters. These results suggest that this novel immunochromatographic device can be effectively used for rapid detection and semi-quantification of P. gingivalis in subgingival plaques. [ABSTRACT FROM AUTHOR]

To assess and compare the anti-microbial efficacy of 445 nm and 970 nm diode laser on mixed species biofilm of Aggregatibacter actinomycetemcomitans [A.a] and Porphyromonas gingivalis [P.g] cultured on machined pure titanium discs. A total of 65 machined pure titanium discs with no surface modifications with a 10-mm diameter and a 2-mm height were sterilized by autoclaving at 121 °C for 15 min and incubated with the commercially available bacterial strains ATCC(American Type Culture Collection- P.g 33277 and A.a 29522)mixture of Aggregatibacter actinomycetemcomitans(A.a) and Porphyromonas gingivalis(P.g).After a 2-week incubation period with the mixture of bacteria to develop a mixed species biofilm, the discs were divided into three groups: (1) no treatment (control), (2) 445 nm laser (test), (3) 970 nm laser (test). For each laser wavelength (445 and 970 nm), the discs were exposed to 1.0 W and 2.0 W in continuous wave mode for the times points of 15, 30, and 60 s. The antimicrobial efficacy was assessed by qPCR. A significant reduction in the levels of both species of bacteria was observed between control and the laser intervention groups. A higher efficacy for the 445 nm diode laser against Porphyromonas gingivalis and a similar efficacy against Aggregatibacter actinomycetemcomitans was observed as compared to the 970 nm group. 445 nm wavelength represents a potential and effective laser wavelength which can be used for the management of peri-implant infection. The present study findings also need to be further validated through clinical interventional trials. [ABSTRACT FROM AUTHOR]

Bee Propolis has been used for its therapeutic properties, including anti‐inflammatory, antibacterial, antifungal, and immune‐stimulating properties, for centuries as a functional food. This study reviewed the effectiveness of propolis as a functional food on oral‐related diseases as a rich bioflavonoid produced by honey bees. A literature search was conducted to identify studies published that investigated the effects of propolis on oral health and its ability to treat related diseases. The search was performed in electronic databases using relevant keywords. Initially, 3429 studies were identified through database searching, and based on the inclusion and exclusion criteria, 22 articles were eligible to be included. Reviewing the articles, propolis was recognized as a functional food and promising agent to balance oral microbiota and prevent oral diseases due to its effectiveness on related bacteria, its anti‐inflammatory properties, and its activity against Porphyromonas gingivalis and Actinomyces Oris allowed it to be an effective substance to prevent periodontal diseases. Based on our findings, Propolis is a desirable preventive option for various oral health conditions, including dental caries and periodontal diseases. Therefore, it is recommended to be consumed as a functional food in our daily diet, which can reduce the risk of oral disease and improve oral health. [ABSTRACT FROM AUTHOR]

Oral diseases stemming from oral pathogenic bacteria pose a significant global health concern, and current methods for managing these pathogens have limitations. Plasma‐activated water (PAW), containing various reactive species, emerges as a promising disinfectant with impressive inactivation capabilities. In this study, PAW prepared by mixed‐mode plasma‐activated gases was applied to inactivate oral pathogenic bacteria, including Streptococcus mutans and Porphyromonas gingivalis. The PAW could reduce more than 6.1‐log10 planktonic bacteria and 4.1‐log10 bacteria within biofilm, respectively, and PAW treatment of planktonic bacteria effectively inhibited biofilm formation. Compared to chlorhexidine, PAW exhibited superior inactivation effects in both planktonic bacteria and biofilm. This study presented a potent strategy for bacteria eradication to reduce the incidence of oral diseases. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the contribution of myeloid differentiation primary‐response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis‐induced experimental periodontitis. Methods: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate‐resistant acid phosphatase (TRAP), the receptor activator of nuclear factor‐kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age‐ and sex‐matched homozygous littermates (wild‐type [WT, Myd88+/+] and Myd88−/− on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. Results: P. gingivalis‐infected Myd88−/− mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88−/− CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL‐10 and IL‐17a expressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88−/− mice. The Myd88−/− mice exhibited characteristic increases in gram‐positive species and species having probiotic properties, while gram‐negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88−/− mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection. Conclusions: MyD88 plays an important role in inflammation‐induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis‐induced experimental periodontitis. [ABSTRACT FROM AUTHOR]

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Objectives: To explore the antimicrobial potential of strontium (Sr)‐functionalized wafers against multiple bacteria associated with per‐implant infections, in both mono‐ and multispecies biofilms. Materials and Methods: The bactericidal and bacteriostatic effect of silicon wafers functionalized with a strontium titanium oxygen coating (Sr‐Ti‐O) or covered only with Ti (controls) against several bacteria, either grown as a mono‐species or multispecies biofilms, was assessed using a bacterial viability assay and a plate counting method. Mono‐species biofilms were assessed after 2 and 24 h, while the antimicrobial effect on multispecies biofilms was assessed at Days 1, 3, and 6. The impact of Sr functionalization on the total percentage of Porphyromonas gingivalis in the multispecies biofilm, using qPCR, and gingipain activity was also assessed. Results: Sr‐functionalized wafers, compared to controls, were associated with statistically significant less viable cells in both mono‐ and multispecies tests. The number of colony forming units (CFUs) within the biofilm was significantly less in Sr‐functionalized wafers, compared to control wafers, for Staphylococcus aureus at all time points of evaluation and for Escherichia coli at Day 1. Gingipain activity was less in Sr‐functionalized wafers, compared to control wafers, and the qPCR showed that P. gingivalis remained below detection levels at Sr‐functionalized wafers, while it consisted of 15% of the total biofilm on control wafers at Day 6. Conclusion: Sr functionalization displayed promising antimicrobial potential, possessing bactericidal and bacteriostatic ability against bacteria associated with peri‐implantitis grown either as mono‐species or mixed in a multispecies consortium with several common oral microorganisms. [ABSTRACT FROM AUTHOR]

Background and Objective: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. Methods: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis‐regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis‐related proteins. Results: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. Conclusion: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis. [ABSTRACT FROM AUTHOR]

Periodontitis is a severe bacterial infection that affects soft tissues around teeth. Periodontitis is caused by a Gram-negative anaerobic bacterium called Porphyromonas gingivalis (P. gingivalis), which promotes the expression of nuclear factor kappa β (NF-κβ). In recent years, medical herbs such as green tea containing Epigallocatechin-3-Gallate (EGCG) have been employed extensively in anti-inflammatory and antibacterial studies due to their low toxicity and strong efficacy based on their multitarget therapy. The mucoadhesive drug delivery system adheres to the surface of the oral mucosa, providing sustained release, enhancing local effects, bypassing first-pass metabolism, and minimizing systemic side effects. This study aimed to investigate the impact of an EGCG-loaded mucosal gingival patch on periodontitis caused by P. gingivalis. Periodontitis was induced in Wistar rats by administering 0.03 mL containing 1010 (CFU) in phosphate-buffered saline (PBS) into the incisive gingival sulcus of the mandible of the anterior teeth. The rats with induced periodontitis received the treatment as mucoadhesive gingival patches loaded with EGCG (GP-EGCG), doxycycline (GP-doxy), and blank patches for one hour daily over 3, 5, 7, 14, and 21 days. Immunohistochemical analysis was performed on the anterior inferior gingival sulcus after the treatment. Results showed that the treatment of periodontitis with GP-EGCG significantly lowered NF-κB expression compared to the control groups following treatment during 3, 5, 7, 14, and 21 days (p < 0.05). EGCG has effectively reduced inflammatory markers in P. gingivalis-induced periodontitis. These findings suggest that the treatment based on EGCG holds promising potential for managing periodontitis, providing an alternative approach to traditional therapies. [ABSTRACT FROM AUTHOR]

Periodontitis-related oral microbial dysbiosis is thought to contribute to adverse pregnancy outcomes (APOs), infertility, and female reproductive inflammation. Since probiotics can modulate periodontitis and oral microbiome dysbiosis, this study examined the effects of a probiotic bacteriocin, nisin, in modulating the reproductive microbiome and inflammation triggered by periodontitis. A total of 24 eight-week-old BALB/cByJ female mice were randomly divided into four treatment groups (control, infection, nisin, and infection+nisin group), with 6 mice per group. A polymicrobial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) mouse model of periodontal disease was used to evaluate the effects of this disease on the female reproductive system, with a focus on the microbiome, local inflammation, and nisin's therapeutic potential in this context. Moreover, 16s RNA sequencing was used to evaluate the changes in the microbiome and RT-PCR was used to evaluate the changes in inflammatory cytokines. Periodontal pathogen DNA was detected in the reproductive organs, and in the heart and aorta at the end of the experimental period, and the DNA was especially elevated in the oral cavity in the infection group. Compared to the control groups, only P. gingivalis was significantly higher in the oral cavity and uterus of the infection groups, and T. forsythia and F. nucleatum were significantly higher in the oral cavity of the infection groups. The infection and nisin treatment group had significantly lower levels of P. gingivalis, T. forsythia, and F. nucleatum in the oral cavity compared with the infection group. Since periodontal pathogen DNA was also detected in the heart and aorta, this suggests potential circulatory system transmission. The polymicrobial infection generally decreased the microbiome diversity in the uterus, which was abrogated by nisin treatment. The polymicrobial infection groups, compared to the control groups, generally had lower Firmicutes and higher Bacteroidota in all the reproductive organs, with similar trends revealed in the heart. However, the nisin treatment group and the infection and nisin group, compared to the control or infection groups, generally had higher Proteobacteria and lower Firmicutes and Bacteroidota in the reproductive organs and the heart. Nisin treatment also altered the microbiome community structure in the reproductive tract to a new state that did not mirror the controls. Periodontal disease, compared to the controls, triggered an increase in inflammatory cytokines (IL-6, TNF-α) in the uterus and oral cavity, which was abrogated by nisin treatment. Polymicrobial periodontal disease alters the reproductive tract's microbial profile, microbiome, and inflammatory status. Nisin modulates the microbial profile and microbiome of the reproductive tract and mitigates the elevated uterine inflammatory cytokines triggered by periodontal disease. [ABSTRACT FROM AUTHOR]

Background: (1) Periodontal disease (PD) is a globally prevalent chronic inflammatory condition, exacerbated by the dysbiosis of the oral microbiota. This study aims to evaluate the bacterial load of specific periodontopathogenic bacteria in patients with malocclusions (MAL) compared to those without. (2) Methods: Conducted at the "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania, this pilot study involved two groups: patients with MAL and PD, and patients with PD but without MAL. We included 20 patients: 10 with MAL (9 with crowding and 1 with an open bite) and 10 without MAL. Gingival crevicular fluid was collected for bacterial DNA extraction and quantified bacterial load using real-time PCR, focusing on 12 periodontopathogenic bacteria across different complexity classes. (3) Results: The study identified significantly higher concentrations of Treponema denticola (p = 0.023, median = 4.32, IQR = 2.76–5.53 vs. median = 1.93, IQR = 0–3.19), Tannerella forsythia (p = 0.020, mean = 6.04 ± 0.72 vs. mean = 4.4 ± 1.89) and Porphyromonas gingivalis (p = 0.002, median = 5.64, IQR = 4.94–5.98 vs. median = 2.48, IQR = 0–4.05) in patients with MAL compared to those without. This suggests that MAL contributes to an environment conducive to the proliferation of specific pathogens, potentially accelerating PD progression. Additionally, Eikenella corrodens (p = 0.040, mean = 4.55 ± 1.02 vs. mean = 3.23 ± 1.56), Campylobacter rectus (p < 0.001, mean = 4.2 ± 0.56 vs. mean = 1.8 ± 1.51), Prevotella intermedia (p = 0.043, median = 5.04, IQR = 0–5.49 vs. median = 0, IQR = 0–3.39), Capnocytophaga sputigena (p = 0.011, median = 5.91, IQR = 5.47–6.17 vs. median = 4.63, IQR = 3.83–5.64), and Capnocytophaga gingivalis (p = 0.007, median = 5.87, IQR = 5.34–6.03 vs. median = 4.4, IQR = 3.5–5.71) also showed elevated concentrations, indicating the broad impacts of MAL on oral microbial profiles. (4) Conclusions: The findings demonstrate a significant relationship between MAL and increased bacterial loads, underscoring the need for its integration in managing PD. Future research should expand demographic diversity and employ longitudinal designs to better understand the causative mechanisms at play. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a keystone pathogen in periodontitis, and Streptococcus sanguinis is an abundant oral commensal bacterium associated with periodontal health. However, the interaction between P. gingivalis and S. sanguinis remains obscure. Here, we established a strategy for high‐throughput measurement of the cell number of P. gingivalis in the coculture with S. sanguinis by detecting the concentration of hydrogen sulfate. The interaction between P. gingivalis and over 2000 S. sanguinis single‐gene mutants was characterized using this strategy, and several interaction‐associated genes in S. sanguinis were determined by detecting more P. gingivalis cells in the coculture with matched S. sanguinis mutants. Three S. sanguinis interaction‐associated genes were predicted to be responsible for cysteine metabolism, and the supplementation of exogenous L‐cysteine promoted the cell number of P. gingivalis in the coculture with S. sanguinis. Thus, exogenous L‐cysteine and the compromised cysteine metabolism in S. sanguinis enhanced the growth of P. gingivalis in the existence of S. sanguinis. Additionally, the interaction between P. gingivalis and other Streptococcus spp. was examined, and S. pneumoniae was the only streptococci that had no inhibition on the cell number of P. gingivalis. In total, this study established a new strategy for high‐throughput screening of the interaction between Streptococcus and P. gingivalis and discovered a set of genes in S. sanguinis that impacted the interaction. The influence of exogenous L‐cysteine on the interaction between P. gingivalis and S. sanguinis in the oral cavity needs further investigation. [ABSTRACT FROM AUTHOR]

Objective: The study delved into the epigenetic factors associated with periodontal disease in two lineages of mice, namely C57bl/6 and Balb/c. Its primary objective was to elucidate alterations in the methylome of mice with distinct genetic backgrounds following systemic microbial challenge, employing high-throughput DNA methylation analysis as the investigative tool. Methods: Porphyromonas gingivalis (Pg)was orally administered to induce periodontitis in both Balb/c and C57bl/6 lineage. After euthanasia, genomic DNA from both maxilla and blood were subjected to bisulfite conversion, PCR amplification and genome-wide DNA methylation analysis using the Ovation RRBS Methyl-Seq System coupled with the Illumina Infinium Mouse Methylation BeadChip. Results: Of particular significance was the distinct methylation profile observed within the Pg-induced group of the Balb/c lineage, contrasting with both the control and Pg-induced groups of the C57bl/6 lineage. Utilizing rigorous filtering criteria, we successfully identified a substantial number of differentially methylated regions (DMRs) across various tissues and comparison groups, shedding light on the prevailing hypermethylation in non-induced cohorts and hypomethylation in induced groups. The comparison between blood and maxilla samples underscored the unique methylation patterns specific to the jaw tissue. Our comprehensive methylome analysis further unveiled statistically significant disparities, particularly within promoter regions, in several comparison groups. Conclusion: The differential DNA methylation patterns observed between C57bl/6 and Balb/c mouse lines suggest that epigenetic factors contribute to the variations in disease susceptibility. The identified differentially methylated regions associated with immune regulation and inflammatory response provide potential targets for further investigation. These findings emphasize the importance of considering epigenetic mechanisms in the development and progression of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. Methods: We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. Results: Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1β, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. Conclusion: The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Nonsurgical periodontal treatment (NSPT) is the gold-standard technique for treating periodontitis. However, an individual's susceptibility or the inadequate removal of subgingival biofilms could lead to unfavorable responses to NSPT. This study aimed to assess the potential of salivary and microbiological biomarkers in predicting the site-specific and whole-mouth outcomes of NSPT. Methods: A total of 68 periodontitis patients exhibiting 1111 periodontal pockets 4 to 6 mm in depth completed the active phase of periodontal treatment. Clinical periodontal parameters, saliva, and subgingival biofilm samples were collected from each patient at baseline and three months after NSPT. A quantitative PCR assay was used to detect the presence of Fusobaterium nucleatum and Porphyromonas gingivalis in the biofilm samples. Salivary biomarkers including matrix metalloproteinase (MMP)-9, glutathione S-transferase (GST), and Annexin-1 were assayed both qualitatively (Western blot analysis) and quantitively (ELISA). Results: NSPT yielded significant improvements in all clinical parameters, including a reduction in bacterial load and decreased levels of MMP-9 together with increased concentrations of GST and Annexin-1. The binary logistic regression suggested that the overall accuracy of P. gingivalis identification, probing pocket depth, and interproximal sites was 71.1% in predicting successful site-specific outcomes. The salivary biomarker model yielded an overall accuracy of 79.4% in predicting whole-mouth outcomes following NSPT. Conclusions: At baseline, the presence of shallow periodontal pockets at interdental locations with a lower abundance of P. gingivalis is predictive of a favorable response to NSPT at the site level. Decreased salivary MMP-9 associated with increased GST and Annexin-1 levels can predict successful whole-mouth outcomes following NSPT. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of SWEEPS mode of the Er: YAG laser(SL) and passive ultrasonic irrigation(PUI) in the eradication of microorganisms and in the inflammation detection by IL-1β. Thirty patients with chronic apical periodontitis(AP) were allocated into two groups: Group SL–SWEEPS laser activated irrigation(n = 15) and Group PUI–passive ultrasonic irrigation(n = 15). Bacteriological samples were taken before(S1) and after chemomechanical preparation(S2), and then after final irrigation activation(S3). The levels of total bacteria and Streptococci were measured by means of PCR. Blood samples were collected before and 3rd day after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-1β. The bacterial reduction showed no differences between groups after chemo-mechanical treatment and after irrigant activation(p = 0.590). Post-treatment IL-1β levels were lower than pretreatment levels in both groups(p < 0.001). SL or PUI application in addition to chemomechanical preparation has similar effects on total bacterial level and inflammation detected by IL-1β in patients with AP. [ABSTRACT FROM AUTHOR]

Introduction: Children with intellectual disability (ID) often face challenges in maintaining proper oral hygiene due to their motor, sensory, and intellectual impairments, which can lead to compromised oral health; therefore, there is a need to enhance the oral health status of these populations and establish an effective system for administering preventive interventions. Here, we aimed to evaluate the prevalence of Entamoeba gingivalis and Trichomonas tenax among children with ID in Lorestan province, in Western Iran through parasitological and molecular methods. Methods: The current descriptive investigation involved 215 in children with ID and 215 healthy children (non-ID) who were referred to health facilities in Lorestan province, Iran between October 2022 and March 2024. The prevalence of protozoa in the oral cavity was found through the utilization of both microscopic analysis and conventional polymerase chain reaction (PCR) techniques. Results: The total prevalence of the E. gingivalis and T. tenax in children with ID was found to be 87 (40.5%) and 92 (42.8%) through microscopic and PCR methods, respectively. Among the positive samples, 57 (61.9%) and 35 (38.1%) children tested positive for E. gingivalis and T. tenax, respectively. In contrast, among the 215 non-ID children in the control group, 39 (18.1%) and 42 (19.5%) tested positive by microscopic and PCR methods, respectively. Among positive samples in non-ID children, 23 (54.7%) and 19 (45.3%) children were positive for E. gingivalis and T. tenax, respectively. Multiple logistic regression analysis indicated that residing in urban areas, parental education, monthly family income, and tooth brushing p<0.001) were identified as independent risk factors for oral cavity parasites. Conclusion: This study identified a notable prevalence of oral cavity parasites in children with ID in Lorestan province, Western Iran. It is imperative to recognize the primary risk factors associated with these parasites, particularly inadequate teeth brushing, in order to enhance public and oral health strategies for children with ID. Therefore, pediatric dental professionals should remain vigilant regarding these risk factors to effectively recognize and address oral health issues in this population, thereby mitigating the occurrence of oral diseases and infections. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post‐treatment infections, and to identify the presence of keystone taxa in both habitats using next‐generation sequencing analysis. Methodology: Apices and periapical lesions of patients with post‐treatment apical periodontitis were surgically extracted. Specimens were cryo‐pulverized, bacterial DNA was extracted, and the V3–V4 hypervariable regions of the 16S rRNA gene were sequenced using the Illumina Miseq platform. Bioinformatic analysis was carried out with Mothur software, whilst diversity indices were obtained using operational taxonomic units (OTUs). The diversity indices were compared with the Kruskal–Wallis test, and community composition differences were explored with Permutational Multivariate Analysis of Variance (PERMANOVA). A bacterial functional study was performed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Co‐occurrence network analyses were performed using the Sparse Correlations for Compositional data (SparCC). Eigencentrality, clr‐based abundance and ubiquitousness were applied to infer keystone taxa. P values <.05 were considered statistically significant. Results: Thirty‐two apices and thirty‐nine periapical lesions were sequenced and analysed. A similar alpha‐diversity (p <.05) and community composition (p =.91) was observed for apices and lesion samples. The most abundant OTUs identified amongst all samples included Fusobacterium nucleatum, Prevotella loescheii, Streptococcus intermedius, Porphyromonas gingivalis, Parvimonas micra, Synergistetes bacterium, Tannerella forsythia and Peptostreptococcus stomatis. The metabolic pathways with >0.81% abundances included membrane transport, genetic information processing and metabolic pathways. F. nucleatum was identified as a keystone taxon as it showed ubiquitousness, an eigenvector centrality value of 0.83 and a clr‐based abundance >4. Conclusions: The microbiome in apices and periapical lesions of post‐treatment endodontic infections showed a similar diversity and taxonomic composition. Co‐occurrence network analyses at OTU level identified F. nucleatum as a keystone taxon candidate in these infections. [ABSTRACT FROM AUTHOR]

Background: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. Methods: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. Results: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 ∩ P.g_3 ∩ H.h_1 ∩ S.a_1 ∩ F.n_2) was 0.722 (95% CI 0.621–0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802–0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663–0.852) in the validation cohort. Conclusions: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China. [ABSTRACT FROM AUTHOR]

Chronic oral inflammation and biofilm-mediated infections drive diseases such as dental caries and periodontitis. This study investigated the anti-inflammatory and antibacterial potential of an ethanol extract from Astilbe chinensis inflorescence (GA-13-6) as a prominent candidate for natural complex substances (NCS) with therapeutic potential. In LPS-stimulated RAW 264.7 macrophages, GA-13-6 significantly suppressed proinflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor (TNF), and nitric oxide (NO), surpassing purified astilbin, a known bioactive compound found in A. chinensis. Furthermore, GA-13-6 downregulated the expression of cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), indicating an inhibitory effect on the inflammatory cascade. Remarkably, GA-13-6 exhibited selective antibacterial activity against Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis, key players in dental caries and periodontitis, respectively. These findings suggest that complex GA-13-6 holds the potential for the treatment or prevention of periodontal and dental diseases, as well as various other inflammation-related conditions, while averting the induction of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived from the interplay between oral microbiota and the host immune response. A comprehensive search of studies published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population. [ABSTRACT FROM AUTHOR]

Aim: Blood–brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. Materials and Methods: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav‐1 levels were measured. The mechanisms of Ddx3x‐induced regulation on Mfsd2a by arginine‐specific gingipain A (RgpA) in BMECs were explored. Results: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up‐regulated Cav‐1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav‐1 regulatory axis was activated. Conclusions: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav‐1 axis. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis and Fusobacterium nucleatum are known to contribute to a variety of tumorigenic pathways linked to the progression of oral squamous cell carcinoma (OSCC). The growing global incidence of antibiotic resistance highlights the critical need to consider the use of antimicrobial peptides (AMPs) as a viable alternative to conventional antibiotics. The current study comprehensively tested Lactobacillus sp.−derived AMPs against bacterially exacerbated OSCC. A total of 52 AMPs were obtained from various databases, and an in silico analysis determined their potent antibacterial and anticancer characteristics after a rigorous screening and pruning approach. Twelve AMPs were tested for 3D structural alignment prediction and validation, with the GH12 synthetic AMP serving as a control. These candidate peptides were thoroughly screened against six important virulence proteins of P. gingivalis and four of F. nucleatum, with the lowest energy score of the docked complexes measuring binding affinity and interactions with active residues being chosen. plpl_18 was determined as the most efficient new AMP that interacted with the virulence protein RagB of P. gingivalis and Fap2 of F. nucleatum with docking scores of −238.24 and −254.27 kcal/mol, respectively. This AMP plpl_18 was docked against selective target OSCC regulatory proteins such as cytokines, metallomatrix proteinase, MAPK, E‐cadherin, and JAK‐1 proteins. Among these proteins, it docked against matrix metalloproteinase‐9 with the highest negative docking scores of −7.5, −260.956, and −1361.9 kcal/mol using AutoDock Vina, HPEPDOCK, and ClusPro 2.0, respectively. Molecular dynamic simulation was used to perform extrapolated validation. These computational studies provide an essential foundation for anticipated laboratory and clinical investigations concerning the possibility of adapting therapeutic peptides based on probiotics to combat the proliferation of OSCC, which is accelerated by F. nucleatum and P. gingivalis. [ABSTRACT FROM AUTHOR]

Background: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti‐inflammatory and antioxidant properties, this study focuses on the potential of a curcumin‐based oral gel in safely managing oral inflammatory conditions. Methods: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin‐based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. Results: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin‐based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line‐specific manner. The curcumin‐based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. Conclusion: This study demonstrates the potential of the curcumin‐based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical‐based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare. [ABSTRACT FROM AUTHOR]

Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells. [ABSTRACT FROM AUTHOR]

Helicobacter pylori has been found to be related to periodontitis, and the oral cavity has been considered a reservoir for H. pylori gastritis infection. Thus, this study evaluated the effect of mouthwash containing poly l -Lysine and glycerol monolaurate on inhibiting H. pylori growth, biofilm formation, cell cytotoxicity, adhesion ability, cag A mRNA expression, and pro-inflammatory cytokines stimulated by H. pylori. Nineteen H. pylori strains were isolated from the oral cavity. The effectiveness of mouthwash containing poly l -Lysine and glycerol monolaurate was examined for its ability to inhibit H. pylori growth and biofilm formation and was tested for cell viability in oral epithelial cells (H357), gastric adenocarcinoma cells (AGS), and periodontal ligament cells (PDL). Additionally, the mouthwash was tested for reducing cag A mRNA expression, adhesion ability to H357 and AGS cells, and pro-inflammatory cytokines stimulated with H. pylori in AGS and PDL cells. The mouthwash containing poly l -Lysine and glycerol monolaurate could eradicate the biofilm by 14.9–19.9% after incubation at 5 min, and cell viability revealed 77.2, 79.8, and 100.0% for AGS, H357, and PDL cells, respectively. Moreover, the mouthwash containing poly l -Lysine and glycerol monolaurate could down-regulate cag A mRNA expression, reduce adhesion of H. pylori by approximately 9.5–47.8% for H357 cells and 24.5–62.9% for AGS cells, and decrease pro-inflammatory cytokines, especially interleukin-8, stimulated with H. pylori. Mouthwash containing poly l -Lysine and glycerol monolaurate could inhibit H. pylori growth and reduce their virulence expression. The mouthwash also revealed low cytotoxicity to oral and gastric cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modulate periodontal bone repair through the hydroxylase domain-containing protein 2 (PHD2)/hypoxia-inducible factor-1 (HIF-1) signalling pathway in response to inflammatory conditions. Methods: Osteogenic differentiation of PHD2 shRNA-modified BMMSCs and the possible mechanism were explored in an inflammatory microenvironment stimulated by porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in vitro. The effect of PHD2 gene-modified BMMSCs on periodontal bone loss was evaluated with experimental periodontitis. Results: Pg-LPS stimulation greatly impaired the osteogenic differentiation of BMMSCs, whereas the silence of PHD2 significantly enhanced the osteogenesis of BMMSCs. More importantly, increased level of vascular endothelial growth factor (VEGF) was detected under Pg-LPS stimulation, which was verified to be associated with the augmented osteogenesis. In experimental periodontitis, PHD2-modified BMMSCs transplantation elevated osteogenic parameters and the expression of VEGF in periodontal tissue. Conclusion: This study highlighted that PHD2 gene silencing could be a feasible approach to combat inflammatory bone loss by rescuing the dysfunction of seed cells. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure P. gingivalis and the flora of P. gingivalis mixed with the symbiotic oral pathogens Fusobacterium nucleatum and Streptococcus mitis. The results showed that the tested flavonoids had little effect on the biofilm amount of pure P. gingivalis, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on P. gingivalis and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against P. gingivalis and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure–activity relationships. [ABSTRACT FROM AUTHOR]

Periodontitis is a severe gum infection leading to chronic inflammation in the gums, damage of tissues around teeth, and destruction of alveolar bones. Porphyromonas gingivalis is the major causative pathogen that induces periodontitis. Numerous probiotic bacteria are reported to produce antibacterial substances against pathogens especially oral pathogens, and these are proposed as preventive measures for periodontitis. In this study, Lacticaseibacillus paracasei LMT18-32 was evaluated and its antibacterial activity against P. gingivalis, and antioxidant activity in vitro were established. In addition, when L. paracasei LMT18-32 was administered to periodontitis induced mice, it successfully alleviated the alveolar bone loss and suppressed induced expression of proinflammatory and tissue destruction related genes in the gingival tissue. In conclusion, L. paracasei LMT18-32 is proposed as a potential probiotics to prevent periodontitis. [ABSTRACT FROM AUTHOR]

Background and Aims: In the case of mucous membrane pemphigoid with gingival expression (gMMP), the complete healing of the gingiva is generally not achieved despite medical treatment. Therefore, patients' oral comfort is impaired. The dysbiotic periodontal microbiota, generated by a lack of oral hygiene associated with persistent gingival pain, could the immunopathological mechanism to persist. The main objective of this study was to characterize the subgingival microbiota of the gMMP patients, and to highlight a potential link between this microbiological data and the clinical data. Methods: Subgingival biofilm was collected from 15 gMMP patients, medically treated or not, but not receiving periodontal treatment. The usual clinical periodontal parameters were recorded. The biofilm was analyzed by polymerase chain reaction quantitative. The risk factors of severe erosive gingivitis and severe periodontitis were assessed using Chi‐square or Fischer's exact test were used. Results: Whatever the medical and periodontal conditions of the patients, the results showed the existence of three main communities of periodontopathic, dysbiotic bacteria. The first including Tannnerella forsythia, Peptostreptococcus micros, Fusobacterium nucleatum, and Campylobacter rectus, was found in 100% of the patients, the second enriched with Treponema denticola in 60% and the third enriched with Porphyromonas gingivalis and Prevotella intermedia in 26%. Furthermore, there was a significant positive link between the duration of gMMP and the severity of erosive gingivitis (p = 0.009), and the loss of deep periodontal tissue (p = 0.04). Conclusion: This pilot study suggests a high periodontal risk in gMMP patients. The pathological processes, autoimmune on the one hand and plaque‐induced on the other, may amplify each other. The application of periodontal therapy is therefore necessary in parallel with medical treatment. Nevertheless, further controlled studies are required to validate and complement these preliminary results. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate the subgingival microbiome in patients with grade C molar‐incisor pattern periodontitis (C‐MIP) affecting the primary or permanent dentitions. Methods: DNA was isolated from subgingival biofilm samples from diseased and healthy sites from 45 C‐MIP patients and subjected to phylogenetic microarray analysis. C‐MIP sites were compared between children affected in the primary to those affected in the permanent dentitions. Within‐subject differences between C‐MIP‐affected sites and dentition‐matched healthy sites were also evaluated. Results: C‐MIP sites of subjects affected in the primary dentition showed partially overlapping but distinct microbial communities from C‐MIP permanent dentition sites (p < 0.05). Differences were due to increased levels in primary C‐MIP sites of certain species of the genera Capnocytophaga and Leptotrichia, while C‐MIP permanent dentition sites showed higher prevalence of Filifactor alocis. Aggregatibacter actinomycetemcomitans (Aa) was among species seen in high prevalence and levels in both primary and permanent C‐MIP sites. Moreover, both permanent and primary C‐MIP sites showed distinct microbial communities when compared to dentition‐matched healthy sites in the same subject (p < 0.01). Conclusions: Primary and permanent teeth with C‐MIP showed a dysbiotic microbiome, with children affected in the primary dentition showing a distinct profile from those affected in the permanent dentition. However, Aa was enriched in both primary and permanent diseased sites, confirming that this microorganism is implicated in C‐MIP in both dentitions. [ABSTRACT FROM AUTHOR]

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of metabolic labeling on Porphyromonas gingivalis (Pg) and compare the imaging effects of two fluorescent probes. Methods This study was reviewed by the unit Ethics Committee and was approved by the Experimental Animal Welfare Ethics Branch of the Unit Experimental Biomedical Ethics Committee. Pg integrated N-azidoacetylgalactosamine (Ac4GalNAz) via a bioorthogonal reaction and was labeled with Cy5-DBCO or Cy7-DBCO via a click chemistry reaction. The bacteria were divided into Pg group (control, not fluorescently labeled), Cy5-Pg group (tagged by Cy5-DBCO), and Cy7-Pg group (tagged by Cy7-DBCO). A live/dead staining kit was applied to test the viability of Pg, Cy5-Pg, and Cy7-Pg. The mRNA levels of interleukin-6 (IL-6) and IL-8 and cell proliferation were examined in human gingival fibroblasts (HGFs) after the challenge of Cy5-Pg, Cy7-Pg, or Pg. To investigate the stability of metabolic labeling, Cy5-Pg or Cy7-Pg was cocultured with Escherichia coli (E. coli). Cy5-Pg and Cy7-Pg signal intensity with serial dilutions were examined using an in vivo imaging system (IVIS). Finally, C57BL/6J mice were orally administered Cy5-Pg or Cy7-Pg for IVIS detection, and the signal-to-background ratios were calculated. Results Metabolic labeling could be applied to label live Pg in vitro. The optimal labeling concentrations for Cy5 and Cy7 were 20 μmol/L and 30 μmol/L, respectively. The area ratios of live to dead bacteria were approximately 2.0 in the three groups (F = 0.318, P>0.05). After a 6-h challenge with Cy5-Pg, Cy7-Pg, or Pg, the mRNA levels of HGFs increased by 7.86-, 7.46-, and 6.56-fold for IL-6, respectively (F = 40.886, PF = 18.781, PP>0.05). HGFs were further challenged by Cy5-Pg, Cy7-Pg, or Pg at different MOIs, and cell proliferation was significantly inhibited (MOI = 104∶1, F = 153.52, P5∶1, F = 331.21, P6∶1, F = 533.65, PP>0.05). Within 24 h of co-culturing Cy5-Pg or Cy7-Pg with E. coli, minimal E. coli was detected. The intensities of Cy5 and Cy7 remained stable for 3 h. Additionally, the fluorescence signal intensities of Cy5 and Cy7 were linearly correlated with the concentration (R2 = 0.97). After oral gavage of Cy5-Pg or Cy7-Pg in mice for the abdominal region at 1 h and 3 h, the signal-to-background ratios of Cy7-Pg were approximately 4.24-fold (t = 6.893, Pt = 4.407, PPg. For the isolated gastrointestinal tracts at 3 h, the signal-to-background ratio of Cy7-Pg was 5.19-fold higher than that of Cy5-Pg (t = 4.418, P

Abstract Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment.