The impact of Thiopeptide antibiotics on inflammatory responses in periodontal tissues through the regulation of the MAPK pathway.

Periodontitis is a bacteria-induced inflammatory disease that damages the tissues supporting the teeth, gums, periodontal ligaments, and alveolar bone. Conventional treatments such as surgical procedures, anti-inflammatory drugs, and antibiotics, are somewhat effective; however, these may lead to discomfort and adverse events, thereby affecting patient outcomes. Therefore, this study aimed to find an effective method to prevent the onset of periodontal disease and explore the specific mechanisms of their action.The impact of thiostrepton on Porphyromonas gingivalis and periodontal ligament stem cells was evaluated in an inflammatory microenvironment. In vivo experiments were performed using a mouse periodontitis model to assess the effectiveness of locally applied thiostrepton combined with a silk fibroin hydrogel in impeding periodontitis progression. Thiostrepton exhibited significant antimicrobial effects against Porphyromonas gingivalis and anti-inflammatory properties by regulating the MAPK pathway through DUSP2. Locally applied thiostrepton effectively impeded the progression of periodontitis and reduced tissue damage. Thiostrepton treatment is a promising and tolerable preventive strategy for periodontitis, offering antimicrobial and anti-inflammatory benefits. These findings suggest the potential of thiostrepton as a valuable addition to periodontitis management, warranting further research and clinical exploration to improve patient outcomes.

Evaluation of the Efficacy of Stem Cells Therapy in the Periodontal Regeneration: A Meta-Analysis and Mendelian Randomization Study.

Stem cell therapy for periodontal defects has shown good promise in preclinical studies. The purpose of this study was to evaluate the impact of stem cell support on the regeneration of both soft and hard tissues in periodontal treatment. PubMed, Cochrane Library, Embase, and Web of Science were searched and patients with periodontal defects who received stem cell therapy were included in this study. The quality of the included articles was assessed using Cochrane's tool for evaluating bias, and heterogeneity was analyzed using the I2 method. An Mendelian randomization investigation was conducted using abstract data from the IEU public databases obtained through GWAS. Nine articles were included for the meta-analysis. Stem cell therapy effectively rebuilds periodontal tissues in patients with periodontal defects, as evidenced by a reduction in probing depth, clinical attachment level  and bone defect depth . And delta-like homolog 1 is a protective factor against periodontal defects alternative indicator of tooth loosening. The findings of this research endorse the utilization of stem cell treatment for repairing periodontal defects in individuals suffering from periodontitis. It is recommended that additional extensive clinical investigations be carried out to validate the efficacy of stem cell therapy and encourage its widespread adoption.

Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis.

Periodontitis is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets.

The impacts of oral and gut microbiota on alveolar bone loss in periodontitis.

Periodontitis, a chronic infectious disease, primarily arises from infections and the invasion of periodontal pathogens. This condition is typified by alveolar bone loss resulting from host immune responses and inflammatory reactions. Periodontal pathogens trigger aberrant inflammatory reactions within periodontal tissues, thereby exacerbating the progression of periodontitis. Simultaneously, these pathogens and metabolites stimulate osteoclast differentiation, which leads to alveolar bone resorption. Moreover, a range of systemic diseases, including diabetes, postmenopausal osteoporosis, obesity and inflammatory bowel disease, can contribute to the development and progression of periodontitis. Many studies have underscored the pivotal role of gut microbiota in bone health through the gut-alveolar bone axis. The circulation may facilitate the transfer of gut pathogens or metabolites to distant alveolar bone, which in turn regulates bone homeostasis. Additionally, gut pathogens can elicit gut immune responses and direct immune cells to remote organs, potentially exacerbating periodontitis. This review summarizes the influence of oral microbiota on the development of periodontitis as well as the association between gut microbiota and periodontitis. By uncovering potential mechanisms of the gut-bone axis, this analysis provides novel insights for the targeted treatment of pathogenic bacteria in periodontitis.

Regulation of the Host Immune Microenvironment in Periodontitis and Periodontal Bone Remodeling.

The periodontal immune microenvironment is a delicate regulatory system that involves a variety of host immune cells including neutrophils, macrophages, T cells, dendritic cells and mesenchymal stem cells. The dysfunction or overactivation of any kind of local cells, and eventually the imbalance of the entire molecular regulatory network, leads to periodontal inflammation and tissue destruction. In this review, the basic characteristics of various host cells in the periodontal immune microenvironment and the regulatory network mechanism of host cells involved in the pathogenesis of periodontitis and periodontal bone remodeling are summarized, with emphasis on the immune regulatory network that regulates the periodontal microenvironment and maintains a dynamic balance. Future strategies for the clinical treatment of periodontitis and periodontal tissue regeneration need to develop new targeted synergistic drugs and/or novel technologies to clarify the regulatory mechanism of the local microenvironment. This review aims to provide clues and a theoretical basis for future research in this field.

CHANGES IN THE ULTRASTRUCTURAL ELEMENTS OF PERIODONTAL NEUROTROPHY UNDER CONDITIONS OF ACUTE SIMPLE COAGULATION DYSTROPHY IN THE EXPERIMENT.

OBJECTIVE: Aim: To determine the role of damage to the ultrastructural elements of the periodontal nervous system in the pathogenesis of dystrophic periodontal disease. PATIENTS AND METHODS: Materials and Methods: The basis of the experimental part of the study was the preparation of ultrathin sections from blocks of gum tissue of white rats, which were prepared using the UMTP-3M device. The study and analysis of biopsy samples was carried out with the help of an electron microscope UEMV-100K. RESULTS: Results: With the help of transmission electron microscopy, it was found that from the first minutes after the injection of hemolysate of isogenic erythrocytes into the rats, aggregates of erythrocytes, clumps of blood plasma, clusters of fibrin monomer masses, bundles of fibrin fibers, platelet and homogeneous were present in the connective tissue of the gums, and in particular in the lumens of hemocapillaries microthrombi, which confirms damage to the ultrastructures of the periodontium, which lead to the development of a pathological process, which is described when simple coagulation dystrophy is reproduced. CONCLUSION: Conclusions: Coagulative damage to the ultrastructural elements of the periodontal nervous system is one of the important factors in the pathogenesis of dystrophic periodontal damage. Under these conditions, trophic disturbances occur, similar to those that occur when the integrity of the nerve is disturbed - neurotrophic mechanism of dystrophy.

Neutrophil N1 and N2 Subsets and Their Possible Association with Periodontitis: A Scoping Review.

Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes.

Raman microspectroscopy/micro-optical coherence tomography approach for chairside diagnosis of periodontal diseases: A pilot study.

BACKGROUND: Our objective was to develop and test a combined Raman microspectroscopy (RMS) and micro-optical coherence tomography (µOCT) approach for chairside quantification of gingival collagen, DNA, epithelium, and connective tissue. We hypothesized that a high-resolution RMS/µOCT can characterize healthy and inflamed periodontal tissues for diagnosis and disease activity monitoring. METHODS: A prototype instrument was developed, tested ex vivo on gingival specimens and optimized for in vivo intraoral use. The primary outcome measures were the ratios of oral epithelium to connective tissue thickness (OE:CT) and the amount of DNA to collagen type I (DNA/Col 1), and the thickness of sulcular epithelium (SE). For ex vivo testing, eight subjects with healthy periodontal tissues or with Stage II to IV periodontitis were included in the study and underwent crown-lengthening or periodontal surgical procedures, respectively. Gingival biopsies were scanned by RMS/µOCT and histometric analyses were performed. The proof-of-concept study included OE/CT, DNA/Col 1, and SE assessed in six volunteers with or without signs of gingival inflammation (n = 3/group). RESULTS: The spatially co-registered RMS spectra revealed opposing changes in the collagen and DNA peaks of inflamed compared with healthy tissues (P <0.05). Combined RMS/µOCT analysis showed that OE/CT, DNA/Col, and SE are significantly different between healthy and inflamed sites (P <0.05). Histological assessments confirmed the differences detected by RMS/µOCT. Qualitative analysis of DNA/Col 1 ratios indicated Col I content as the main distinguishing feature for health and DNA content for periodontitis. CONCLUSION: Results suggest that combined RMS/µOCT chairside imaging may distinguish between healthy and diseased sites by evaluating marginal periodontal morphological and biochemical features.

Efecto de la hipoxia sobre los tejidos de la cavidad oral: revisión de la literatura / Effect of hypoxia on oral tissues: a review of the literature

La exposición a hipoxia es considerada un estímulo estresante, por lo que el organismo desarrolla meca-nismos de aclimatación para asegurar la homeosta-sis. Si bien el efecto de la hipoxia sobre los distintos sistemas de tejidos y órganos ha sido bien documen-tado, el rol de los bajos niveles de O2 en la cavidad oral no ha recibido el mismo análisis. En este trabajo se revisaron los datos bibliográficos disponibles sobre el efecto de la hipoxia sobre el tejido periodontal, las glándulas salivales, la pulpa dental y el hueso mandi-bular y alveolar. De lo analizado en la bibliografía, re-sulta evidente que los bajos niveles de O2 aumentan el número de mediadores inflamatorios que inducen la progresión de la enfermedad periodontal y, a su vez, la inflamación establecida durante dicha enfermedad agrava aún más las condiciones de hipoxia tisular. Las glándulas salivales también se encuentran afectadas durante la exposición a hipoxia, disminuyendo la can-tidad de saliva secretada, observándose alteraciones ultraestructurales en el parénquima glandular. Por otra parte, se ha establecido que la hipoxia puede te-ner efectos deseados para el cultivo de células madre de la pulpa dental, lo cual resulta útil en el campo de la odontología reparativa y también para el movimien-to dental durante los tratamientos ortodónticos. En conclusión, para determinar los efectos de la hipoxia en la cavidad oral se debe analizar no sólo el tipo de tejido involucrado sino también las condiciones de hi-poxia a las cuales éste es sometido, así también como la duración de la exposición y la modalidad de hipoxia (AU)

Exposure to hypoxia is considered a stressful stimulus, therefore the organism develops acclimation mechanisms to try to ensure homeostasis. Although the effect of hypoxia on different tissues and organs has been very well documented, the role of low levels of O2 in the oral cavity has not received the same analysis. In this review, we analyzed the available bibliographic data concerning the effects of hypoxia on periodontal tissue, salivary glands, and dental pulp. The published evidence demonstrates that low O2 levels increase the number of inflammatory mediators that induce the progression of periodontal disease, and, in turn, the inflammation established during the progression of periodontitis aggravates tissue hypoxia conditions. Salivary glands are also affected during hypoxic exposure, decreasing salivary secretion, and leading to ultrastructural alterations in the glandular parenchyma. On the other hand, hypoxia could also be beneficial in some scenarios. It has been established that dental pulp cells grow better in culture under hypoxic conditions than they do in normoxia. Furthermore, mild hypoxia seems to stimulate periodontal ligament cells proliferation and matrix degradation, key events during for orthodontic treatments. In conclusion, to determine the effects of hypoxia in the oral cavity, it is necessary to analyze not only the type of tissue involved but also the hypoxic conditions to which it is subjected, as well as its duration and modality (AU)

Improved Healing after Non-Surgical Periodontal Therapy Is Associated with Higher Protein Intake in Patients Who Are Non-Smokers.

The aim of this study was to determine whether a relationship between periodontal healing and protein intake exists in patients undergoing non-surgical treatment for periodontitis. Dietary protein intake was assessed using the 2005 Block food frequency questionnaire in patients with chronic generalized periodontitis undergoing scaling and root planing (n = 63 for non-smokers, n = 22 for smokers). Protein intake was correlated to post-treatment probing depth using multiple linear regression. Non-smoking patients who consumed ≥1 g protein/kg body weight/day had fewer sites with probing depth ≥ 4 mm after scaling and root planing compared to patients with intakes <1 g protein/kg body weight/day (11 ± 2 versus 16 ± 2, p = 0.05). This relationship was strengthened after controlling for baseline probing depth, hygienist and time between treatment and follow-up (10 ± 2 versus 16 ± 1, p = 0.018) and further strengthened after controlling for potential confounders including age, sex, body mass index, flossing frequency, and bleeding on probing (8 ± 2 versus 18 ± 2, p < 0.001). No associations were seen in patients who smoked. Consuming ≥1 g protein/kg body weight/day was associated with reductions in periodontal disease burden following scaling and root planing in patients who were non-smokers. Further studies are needed to differentiate between animal and plant proteins.

Recombinant factors for periodontal intrabony defects: A systematic review and network meta-analysis of preclinical studies.

The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm2 ), bone volume density (g/cm3 ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose.

Recombinant Human Derived Growth and Differentiating Factors in treatment of periodontal intrabony defects: Systematic review and network meta-analysis.

The introduction of recombinant human growth and differentiation factors (rhGFs) for intrabony defects regeneration has represented a considerable breakthrough in recent years. However, they have been used in different concentrations, doses and combined with various scaffolds, and there is no evidence on which the most effective formulation for periodontal regeneration is. Therefore, we aimed to evaluate and rank the various formulations of such bioactive agents through network meta-analysis of clinical studies. The protocol registration was done on PROSPERO with registration ID CRD42020213753. To report NMA, we followed PRISMA guidelines and searched PUBMED, Embase, Web of Science and Cochrane Central electronic databases. Studies were screened based on specific inclusion criteria. Primary outcomes extracted from included studies were the most common indexes for periodontal regeneration (PPD, CAL, %bone filling). The NMA analysis included network plots, contribution plots, inconsistency plots (if eligible to form the loop), predictive interval plots, SUCRA rankings and multidimensional scale ranking (MDS) plots. SUCRA would demonstrate the rankings of multiple competing bioactive agents based on their best performance. Twelve clinical studies for qualitative and quantitative analysis were considered. Network meta-analysis found that rhFGF + hyaluronic acid was ranked highest in PPD and CAL outcome. rhPDGF-BB + ß-tricalcium phosphate was ranked highest in the percentage of bone filling. In addition, all bioactive agents performed better than control groups without rhGFs. Despite clear benefits deriving from rhGFs for periodontal regeneration, the present results should be interpreted with caution due to several confounding factors affecting the outcome. Nevertheless, further well designed randomized clinical trials will allow establishing guidelines for an appropriate indication of the use of rhGFs.

Periodontal Inflamed Surface Area Mediates the Link between Homocysteine and Blood Pressure.

Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001-2002 and 2003-2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood pressure (BP) and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and BP. Mediation analysis was performed to understand the effect of PISA and PESA in the link between Hcy and BP. 4021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models (p < 0.01), but not PISA (p > 0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%. In conclusion, Hcy and periodontitis are associated. Further, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which Hcy levels increase in a clinical situation of periodontitis.

Crosstalk between RNA-Binding Proteins and Immune Microenvironment Revealed Two RBP Regulatory Patterns with Distinct Immunophenotypes in Periodontitis.

Periodontitis is an inflammatory disease whose pathogenesis is closely related with immunology. RNA-binding proteins (RBPs) were found to play crucial roles in immunity. Therefore, we aimed to investigate the potential impact of RBPs in the immune microenvironment in periodontitis. The differential expressions of RBPs in periodontitis and healthy samples were determined and were used to construct an RBP-based classifier for periodontitis using logistic regression. The correlations between RBPs and immune characteristics were investigated by the Spearman correlation. Unsupervised clustering was conducted to identify the RBP regulatory patterns. RBP-related genes were identified by WGCNA, while biological distinctions were revealed by GSVA and GO. 24 dysregulated RBPs were identified, from which a 12-RBP classifier was established to distinguish periodontitis with AUC of 0.942. Close protein-protein interactions and expression correlations were observed especially between SPATS2 and ISG20. ISG20 and ESRP1 were found to be highly correlated with immunocyte infiltration, immune signaling activation, and HLA expressions in periodontitis. Two distinct RBP regulatory patterns were identified with different immune and other biological characteristics in periodontitis. Our findings indicate a significant impact of RBPs in shaping the immune microenvironment in periodontitis, which might bring new insights into the understanding of immune mechanisms in the pathogenesis of periodontitis.

Healing of Experimental Periodontal Defects Following Treatment with Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral.

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation.

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues.

Among oral tissues, the periodontium is permanently subjected to mechanical forces resulting from chewing, mastication, or orthodontic appliances. Molecularly, these movements induce a series of subsequent signaling processes, which are embedded in the biological concept of cellular mechanotransduction (MT). Cell and tissue structures, ranging from the extracellular matrix (ECM) to the plasma membrane, the cytosol and the nucleus, are involved in MT. Dysregulation of the diverse, fine-tuned interaction of molecular players responsible for transmitting biophysical environmental information into the cell's inner milieu can lead to and promote serious diseases, such as periodontitis or oral squamous cell carcinoma (OSCC). Therefore, periodontal integrity and regeneration is highly dependent on the proper integration and regulation of mechanobiological signals in the context of cell behavior. Recent experimental findings have increased the understanding of classical cellular mechanosensing mechanisms by both integrating exogenic factors such as bacterial gingipain proteases and newly discovered cell-inherent functions of mechanoresponsive co-transcriptional regulators such as the Yes-associated protein 1 (YAP1) or the nuclear cytoskeleton. Regarding periodontal MT research, this review offers insights into the current trends and open aspects. Concerning oral regenerative medicine or weakening of periodontal tissue diseases, perspectives on future applications of mechanobiological principles are discussed.

Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation.

Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The "red complex" and "cluster B" abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.

Diabetes induces macrophage dysfunction through cytoplasmic dsDNA/AIM2 associated pyroptosis.

Diabetes is emerging as a severe global health problem that threatens health and increases socioeconomic burden. Periodontal impairment is one of its well-recognized complications. The destruction of the periodontal defense barrier makes it easier for periodontal pathogens to invade in, triggering a greater inflammatory response, and causing secondary impairment. Macrophages are the major immune cells in periodontium, forming the frontier line of local innate immune barrier. Here, we explored the periodontal impairments and functional changes of macrophages under the diabetic and aging conditions. Besides, we further explored the molecular mechanism of how hyperglycemia and aging contribute to this pathogenesis. To test this, we used young and aged mice to build diabetic mice, and metformin treatment was applied to a group of them. We demonstrated that under hyperglycemia conditions, macrophage functions, such as inflammatory cytokines secretion, phagocytosis, chemotaxis, and immune response, were disturbed. Simultaneously, this condition elevated the local senescent cell burden and induced secretion of senescence-associated secretory phenotype. Meanwhile, we found that expressions of Gasdermin D (GSDMD) and caspase-1 were up-regulated in diabetic conditions, suggesting that the local senescent burden and systemic proinflammatory state during diabetes were accompanied by the initiation of pyroptosis. Furthermore, we found that the changes in aged condition were similar to those in diabetes, suggesting a hyperglycemia-induced pre-aging state. In addition, we show that metformin treatment alleviated and remarkably reversed these functional abnormalities. Our data demonstrated that diabetes initiated macrophage pyroptosis, which further triggered macrophage function impairments and gingival destructions. This pathogenesis could be reversed by metformin.

Controlled release of iodine from cross-linked cyclodextrin metal-organic frameworks for prolonged periodontal pocket therapy.

Effective therapeutic system to periodontitis was designed using cross-linked cyclodextrin metal-organic framework (COF) as carrier for iodine and further suspended in hydroxyethyl cellulose gel as I2@COF-HEC hydrogel. Inclusion of iodine within the COF was demonstrated by SR-FTIR spectral and characteristic DSC and TGA changes. Molecular modelling identified the interaction of iodine with both COF central cavity and individual cyclodextrin moieties of COF. In vitro results of study demonstrated that iodine release in artificial saliva from I2@COF-HEC hydrogel could be extended up to 5 days, which was slower than I2@COF particles. Using an in vivo rat model of periodontitis, micro-computed tomography of alveolar bone morphology demonstrated that I2@COF-HEC hydrogel showed similar effects in decreasing periodontal pocket depth and alveolar bone resorption to minocycline ointment, a periodontitis antibiotic. The I2@COF-HEC hydrogel is a novel local delivery device of iodine as a broad spectrum antimicrobial use for treatment of periodontitis.

Milk Kefir therapy reduces inflammation and alveolar bone loss on periodontitis in rats.

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues. This study evaluated the anti-inflammatory and antiresorptive effects of milk kefir (MK) on periodontitis in rats. Micro-Raman spectroscopy was performed on MK at different fermentation times to verify the presence of Lactobacillus kefiri. From these results, Wistar rats were divided into the following groups: C (Control); EP (experimental periodontitis); K1 (animals that received MK with one day of fermentation); K1+EP; K4 (animals without EP using MK with four days of fermentation) and K4+EP. MK was administered 28 days before EP induction and during the disease development period (11 days). On day 28, in the EP groups, periodontitis was induced. The animals were euthanized on day 39. The hemimaxillae were removed and the following parameters were evaluated: micro-Raman analysis of the presence of inflammation; histomorphometric analysis to quantify alveolar bone loss and immunohistochemistry for IL-6, TNF-α, IL-Iß and IL-10 in the periodontal ligament. Micro-Raman analysis showed that four days fermentation MK has a higher intensity spectrum of L. kefiri. Furthermore, the administration of this probiotic reduced the intensity of the inflammation spectrum when compared to one day fermentation MK. It was observed that the animals from the K4+EP group showed significant reduction of alveolar bone loss, as well as a lower IL-6, TNF-α and IL-Iß immunoexpression and a higher IL-10 immunoexpression, when compared to EP groups. We conclude that MK has anti-inflammatory and antiresorptive effects on periodontitis in rats and that these effects are fermentation time dependent.