scholarly journals Hypoxia andP. gingivalisSynergistically Induce HIF-1 and NF-κB Activation in PDL Cells and Periodontal Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
L. Gölz ◽  
S. Memmert ◽  
B. Rath-Deschner ◽  
A. Jäger ◽  
T. Appel ◽  
...  
Keyword(s):  
Target Genes ◽  
Periodontal Diseases ◽  
Anaerobic Bacteria ◽  
Periodontal Pathogen ◽  
Tissue Samples ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Matrix Metalloproteinase 1 ◽  
Pdl Cells

Periodontitis is characterized by deep periodontal pockets favoring the proliferation of anaerobic bacteria likePorphyromonas gingivalis(P. gingivalis), a periodontal pathogen frequently observed in patients suffering from periodontal inflammation. Therefore, the aim of the present study was to investigate the signaling pathways activated by lipopolysaccharide (LPS) ofP. gingivalis(LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant transcription factors nuclear factor-kappa B (NF-κB) and hypoxia inducible factor-1 (HIF-1) were determined. In addition, we analyzed the expression of interleukin- (IL-) 1β, matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was accomplished by immunohistochemistry of healthy and inflamed periodontal tissues. We detected time-dependent additive effects of LPS-PG and hypoxia on NF-κB and HIF-1αactivation in PDL cells followed by an upregulation of IL-1β, MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of gingivitis and periodontitis displayed an increase of NF-κB, HIF-1, and VEGF immunoreactivity in accordance with disease progression validating the importance of thein vitroresults. To conclude, the present study underlines the significance of NF-κB and HIF-1αand their target genes VEGF, IL-1β, and MMP-1 inP. gingivalisand hypoxia induced periodontal inflammatory processes.

scholarly journals Role of Cathepsin S in Periodontal Inflammation and Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
S. Memmert ◽  
A. Damanaki ◽  
A. V. B. Nogueira ◽  
S. Eick ◽  
M. Nokhbehsaim ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Interleukin 1 ◽  
Critical Role ◽  
Gingival Tissue ◽  
Cathepsin S ◽  
Protein Levels ◽  
Periodontal Inflammation

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.

Compressive Force Induces VEGF Production in Periodontal Tissues

2009 ◽  
Vol 88 (8) ◽  
pp. 752-756 ◽  
Author(s):  
A. Miyagawa ◽  
M. Chiba ◽  
H. Hayashi ◽  
K. Igarashi
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Vascular System ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Vegf Mrna ◽  
Angiogenic Activity ◽  
Periodontal Tissues ◽  
Pdl Cells

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.

scholarly journals Innate Immune Response as a New Challenge in Periodontal Inflammation

2021 ◽  
Author(s):  
Ana Marina Andrei ◽  
Elena Cristina Andrei ◽  
Elena Camelia Stănciulescu ◽  
Mihaela Cezarina Mehedinți ◽  
Mihaela Jana Țuculină ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Periodontal Diseases ◽  
Bacterial Species ◽  
Innate Immune ◽  
Beneficial Effects ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Genetic And Environmental Factors ◽  
Tlr Signalling

Gingivitis and periodontitis are induced by numerous pathogenic microbiota hosted in the subgingival biofilm that first trigger the innate immune response. Innate immune response is part of a homeostatic system which is the first line defence and defines the host inherited resistance to infection. Both genetic and environmental factors are involved in variable individual susceptibility to inflammation of periodontal tissues. That is why, although more than 600 bacterial species have been detected in the periodontal plaque, the type of bacteria incriminated in the development of the inflammation is still unclear. Moreover, in the last decade gene polymorphisms have been largely recognised as important conditions associated with increased susceptibility to periodontal diseases. Manipulating the immune response by the development of drugs that inhibit adverse host reactions and promote beneficial effects might be of therapeutic or prophylactic importance. This work intends to assess the importance of Toll-like receptors as main effectors of the innate immune response in the triggering, maintenance and progression of periodontal inflammation, as well as of the involvement of synthetic molecules targeting TLR signalling pathways in treating periodontal diseases.

scholarly journals LPS fromP. gingivalisand Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
L. Gölz ◽  
S. Memmert ◽  
B. Rath-Deschner ◽  
A. Jäger ◽  
T. Appel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Periodontal Ligament ◽  
Inflammatory Diseases ◽  
Periodontal Pathogen ◽  
Oral Diseases ◽  
Redox Systems ◽  
Periodontal Ligament Fibroblasts ◽  
Prolonged Incubation ◽  
Periodontal Tissues ◽  
Pdl Cells

Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide fromPorphyromonas gingivalis(LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P<0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P<0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases.

The impact of the viral-bacterial consortium on occurrence and development of chronic periodontitis

2020 ◽  
Vol 25 (2) ◽  
pp. 84-89
Author(s):  
V. N. Tsarev ◽  
E. A. Yagodina ◽  
T. V. Tsareva ◽  
E. N. Nikolaeva
Keyword(s):  
Pathogenic Bacteria ◽  
Periodontal Diseases ◽  
Bacterial Consortium ◽  
Progressive Increase ◽  
Bacterial Biofilm ◽  
Herpes Simplex Viruses ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Immunological Mechanisms ◽  
The Impact

Relevance. The current theory of specific bacterial biofilm fails explain why a part of patients experiences inflammatory periodontal diseases while the absence of detected specific types of “red complex” bacteria.Purpose. To clarify the microbiological and immunological mechanisms of the influence of the viral and bacterial consortium in the etiology and pathogenesis of inflammatory periodontal diseases.Materials and methods. Articles survey with elements of metanalisis. Literature review based on discussion of research results on the topic of 48 sources including 33 foreign ones.Results. The review provides evidences of the possible participation of viruses of the Herpesviridae family in the development of chronic generalized periodontitis. Evidences for the role of herpes simplex viruses of type 1.2, Epstein-Barr virus, and cytomegalovirus in the development of periodontal inflammation are analyzed. It is proven that all herpesviruses induce the release of proinflammatory cytokines that activate osteoclasts and matrix metalloproteinases, as well as violate antibacterial immune mechanisms. In turn that leads to a progressive increase of periodontal pathogenic bacteria in both the biofilm and periodontal tissues.Conclusion. It is made a conclusion that an active herpetic infection can initiate damage to periodontal tissus and participate in the development of relapses of the disease.

scholarly journals Inconsistency in Expression Pattern of a Five-lncRNA Signature As a Potential Diagnostic Biomarker for Gastric Cancer Patients in Bioinformatics and in Vitro

2021 ◽  
Author(s):  
Mahmoud Ghanei ◽  
Arash Poursheikhani ◽  
Azadeh Aarabi ◽  
Negin Taghehchian ◽  
Mohammad Reza Abbaszadegan
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Target Genes ◽  
P Value ◽  
Diagnostic Biomarker ◽  
Tissue Samples ◽  
Specificity And Sensitivity ◽  
Gastric Cancer Patients

Abstract BACKGROUND: Due to the diagnosis of gastric cancer in advance stages as well as its poor prognosis, finding biomarkers is essential.OBJECTIVE: In this study, using the TCGA RNAseq data of gastric cancer patients, we evaluated the diagnostic value of lncRNAs which had differential expression.METHODS: we evaluated P value, FDR, log fold change for whole transcripts. Next, by comparison of the RNAseq gene names with total known lncRNA names, we identified differntial expressed lncRNAs. Folowing, we calculated specificity and sensitivity for lncRNAs came from previous step. For more confirmation, we predict target genes and performed GO and KEGG signalling pathway analysis. At the end, we examined the reliability and consistency of expression of this signature in three gastric cancer cell lines and one of them in twenty tumoric and tumor adjacent normal tissue samples using qRT-PCR.RESULTS: Five lncRNAs had proper sensitivity and specificity and had target genes involved in cancer-related signaling pathways; however, they showed different expression pattern in TCGA data and in vitro.CONCLUSIONS: The results of our study demonstrated that the five-lncRNAs PART1, UCA1, DIRC3, HOTAIR, and HOXA11AS require more investigation to be confirmed as a diagnostic biomarker in gastric cancer.

scholarly journals Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis - Immunomodulatory Effects, Animal and Clinical Studies

2020 ◽  
Author(s):  
Izabela Nawrot-Hadzik ◽  
Adam Matkowski ◽  
Paweł Kubasiewicz-Ross ◽  
Jakub Hadzik
Keyword(s):  
Clinical Studies ◽  
Periodontal Diseases ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Grape Seeds ◽  
Periodontal Tissues ◽  
Bacterial Proliferation ◽  
Major Response ◽  
Black Other

This paper continues the review study on antimicrobial properties relevant to the periodontal diseases. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response has been covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies has been analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there is still much less studies using animal models and only a few clinical studies. Most of the studies, regardless of the used model indicated efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontitis is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.

scholarly journals Regulation Network of Colorectal-Cancer-Specific Enhancers in the Progression of Colorectal Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8337
Author(s):  
Bohan Chen ◽  
Yiping Ma ◽  
Jinfang Bi ◽  
Wenbin Wang ◽  
Anshun He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Target Genes ◽  
Colorectal Cancer Cell Line ◽  
Tissue Samples ◽  
Colon Cells ◽  
Colorectal Cancer Cells ◽  
Regulation Network

Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer–promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis

2021 ◽  
pp. 1-10
Author(s):  
Jia-Bin Zhan ◽  
Jing Zheng ◽  
Lian-Ya Zeng ◽  
Zhi Fu ◽  
Qiu-Ju Huang ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Target Genes ◽  
Mammalian Target Of Rapamycin ◽  
Ar Model ◽  
Target Of Rapamycin ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Interacting Protein ◽  
Human Nasal Epithelial Cells

<b><i>Background:</i></b> This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). <b><i>Methods:</i></b> Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). <b><i>Results:</i></b> The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. <b><i>Conclusions:</i></b> The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.

β-defensins and the inflammatory periodontal diseases: a systematic review

2020 ◽  
Vol 25 (4) ◽  
pp. 276-286
Author(s):  
E. A. Tikhomirova ◽  
E. S. Slazhneva ◽  
V. G. Atrushkevich
Keyword(s):  
Antimicrobial Peptides ◽  
Periodontal Diseases ◽  
Steady Increase ◽  
Periodontal Pathogens ◽  
Periodontal Tissues ◽  
Treatment And Prevention ◽  
Concomitant Factors ◽  
Google Search

Relevance. The steady increase in the number of inflammatory periodontal diseases (IPD) requires the search for new methods of their diagnosis, treatment and prevention. A large number of antimicrobial peptides are expressed in the oral cavity, including β-defensins, which form the first line of defense against periodontal pathogens. A more detailed study of these proteins will help us to answer the question: why this protective barrier breaks through and may we use β-defensins as markers of IPD. The aim is to study information about the role of β-defensins in the pathogenesis of IBD and to evaluate the possibility of their use as biomarkers of these diseases.Materials and methods. Using search systems as PubMed, Google Search and eLIBRARY were found 2106 articles published between 2003 and 2020 years. According to the inclusion and non-inclusion criteria, 39 publications were selected, including in vivo, in vitro and review articles. This review presents data from the selected articles.Results. β-defensins have antimicrobial activity against periodontal pathogens, but these bacteria can change the expression of the antimicrobial peptides or can be the cause of their destruction due to virulence factors. In addition, the concentration of β-defensins may be affected by the cytokines, synthesized during inflammation in periodontal tissues. Compared with individuals without IPD the patients with chronic generalized gingivitis, aggressive and chronic generalized periodontitis most often have changes in the expression of β-defensins both up and down, which also depends on the stage of the inflammatory process.Conclusion. β-defensins play an important role in the antimicrobial protection of periodontal tissues from the introduction of periodontal pathogens and can be used as markers of IBD. However evaluating the concentration of defensins in the oral fluid, it is necessary to take into account concomitant factors: the presence of periodontal pathogens, the presence of certain cytokines, the stage of the disease, the presence of concomitant pathology and the genetic aspect.

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