☆ 4.5 Review

Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Oral health status and the etiology and prevention of nonventilator hospital-associated pneumonia

Frank A. Scannapieco et al.

Summary: Nonventilator hospital-associated pneumonia has become an important preventable hospital-associated infection and a leading cause of healthcare-associated infection. Poor oral health is linked to an increased risk of pneumonia caused by different pathogens. Oral care plays a crucial role in preventing nonventilator hospital-associated pneumonia.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Periodontal microorganisms and Alzheimer disease - A causative relationship?

Gert Jungbauer et al.

Summary: The impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease is still unclear. Factors contributing to microbial dysbiosis include aging, local inflammation, systemic diseases, wearing dentures, living in nursing homes, and poor oral hygiene measures. Porphyromonas gingivalis has been detected in post-mortem brain samples, and there is a difference in microbial composition between Alzheimer disease and cognitively healthy individuals. In-vitro and animal studies suggest the potential of P. gingivalis to induce Alzheimer disease-related alterations. Further clinical trials are needed to explore the effects of periodontal therapy on the oral microbiome and cognitive parameters.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis

Emmanuel Albuquerque-Souza et al.

Summary: The liver plays a crucial role in metabolism, nutrient storage, and detoxification, as well as immune surveillance. Unresolved inflammation in the liver can lead to chronic liver diseases, and there is emerging evidence suggesting an association between oral health and liver diseases. The presence of chronic inflammation and dysbiotic microbiota in the oral cavity can impact the onset and progression of liver diseases, including nonalcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and hepatocellular cancer.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Viruses, periodontitis, and comorbidities

Flavia Teles et al.

Summary: Studies have shown a connection between periodontal diseases and systemic conditions, suggesting that these oral diseases may contribute to the development of systemic diseases. The bacterial infection and inflammation caused by periodontal diseases are believed to play a role in the pathogenesis of these systemic conditions. Furthermore, viruses in the oral cavity might also have a similar impact in connecting periodontal diseases and systemic conditions.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma

Richard J. Lamont et al.

Summary: Oral and esophageal squamous cell carcinomas have a distinct microbiome composition compared to precancerous and healthy tissues. Porphyromonas gingivalis, a periodontal pathogen, is associated with the cancerous state and poor prognosis. In vitro and in vivo studies have shown that P. gingivalis may promote tumor development through various mechanisms. The microbial community context also plays a role in oncogenicity, with some bacteria having protumorigenic or antagonistic effects. Metatranscriptomic data suggests that functional properties of tumor-associated communities are more relevant to cancer development than compositional properties. The consistent association of P. gingivalis with oral and orodigestive carcinoma could have diagnostic potential for early detection.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia

Pirkko J. Pussinen et al.

Summary: Lipopolysaccharide is a virulence factor of gram-negative bacteria that is crucial for the integrity of the bacterial surface. It activates both innate and adaptive immunity and can trigger inflammation directly or indirectly. Chronic endotoxemia, which is associated with an increased risk of inflammation-driven diseases, particularly cardiometabolic disorders, has been linked to the gut microbiota as the main source. Oral dysbiosis in periodontitis may also contribute to endotoxemia. This suggests that lipopolysaccharide could be a molecular link between periodontal microbiota and cardiometabolic diseases.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Periodontal connection with intestinal inflammation: Microbiological and immunological mechanisms

Sho Kitamoto et al.

Summary: Human beings have evolved together with trillions of resident microbes that inhabit every part of the body, forming a symbiotic relationship that benefits human physiology. However, disturbances in the resident microbiota can have serious consequences, affecting both local and distant ecosystems. This article examines the connection between periodontal disease and intestinal inflammation from microbiological and immunological perspectives. It also explores potential therapeutic approaches to treat gastrointestinal diseases by targeting the connection between the mouth and the gut. Understanding the complex interplay between microbes and immunity along the mouth-gut axis can provide insights into the pathogenesis of oral and gut pathologies and offer potential therapeutic opportunities.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: Immunotherapeutic implications

Ahmed R. El-Awady et al.

Summary: Extensive research has revealed the complex mechanisms behind the immunopathogenesis of periodontitis. Dendritic cells play a crucial role in this process, being invaded by Porphyromonas gingivalis and releasing exosomes that promote immune cell senescence and bone loss. These findings contribute to the development of new immunotherapeutic approaches for promoting human health and longevity.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Osteoporosis and periodontal diseases - An update on their association and mechanistic links

Bo Yu et al.

Summary: Periodontitis and osteoporosis are inflammation-associated skeletal disorders prevalent in the aging population. Systemic low bone mineral density is correlated with alveolar bone loss and inflammation plays a critical role in bone remodeling in both conditions. Shared risk factors such as vitamin D deficiency and smoking may mediate the connection between osteoporosis and periodontitis.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Fusobacterium nucleatum and cancer

Tamar Alon-Maimon et al.

Summary: Accumulating evidence suggests that the oral pathobiont Fusobacterium nucleatum plays a crucial role in the progression of various tumor types by enhancing tumor proliferation, creating a tumor-promoting immune environment, inducing chemoresistance, and activating immune checkpoints. This review focuses on understanding the mechanisms underlying tumor-specific colonization and promotion by fusobacteria, which could lead to the development of novel approaches for tumor detection and treatment.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Oral bacteria, oral health, and adverse pregnancy outcomes

Biyang Xu et al.

Summary: Numerous epidemiological studies suggest a link between oral health and adverse pregnancy outcomes. Recent studies indicate a relationship between the severity of periodontal disease and adverse pregnancy outcomes. Two virulence mechanisms are proposed: direct invasion of oral microorganisms or their components into the fetal-placenta unit and inflammatory mediators produced in the oral cavity affecting the fetal-placenta unit. While interventional periodontal therapy still yields contradictory results, animal studies suggest that maternal supplementation of omega-3 fatty acids protects the fetus by suppressing inflammation and bacteria proliferation in the placenta.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Pros and cons of causative association between periodontitis and rheumatoid arthritis

Joanna Koziel et al.

Summary: Recent research has made significant advancements in understanding the molecular basis of autoimmune diseases, especially rheumatoid arthritis. New studies suggest that a more comprehensive and interdisciplinary approach is needed to understand the pathobiology of rheumatoid arthritis, including bacteria-induced inflammatory reactions as an important pathway. This article discusses the clinical and molecular association between periodontal diseases and the development of rheumatoid arthritis, as well as the unique role of periopathogens in the initiation and progression of this autoimmune disorder.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities

George Hajishengallis et al.

Summary: This article reviews the bidirectional association between periodontitis and systemic inflammatory disorders. It introduces two newly emerged concepts, trained innate immunity (TII) and clonal hematopoiesis of indeterminate potential (CHIP), which together support a potential hypothesis on how periodontitis affects and is affected by comorbidities and why the susceptibility to periodontitis and comorbidities increases with aging. The article discusses the role of TII and CHIP in mediating the relationship between periodontitis and comorbidities, and proposes that a mechanistic understanding of this connection may lead to novel diagnostic and therapeutic targets for inflammatory comorbidities.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Periodontitis and coronavirus disease 2019

Faleh Tamimi et al.

Summary: There is a possible association between coronavirus disease 2019 and periodontitis, possibly due to their shared characteristics of inflammation and systemic effects. Studies suggest that periodontal disease may impact the severity of COVID-19. Further research is needed to confirm these observations and explore the potential role of periodontal care in the COVID-19 pandemic.

PERIODONTOLOGY 2000 (2022)

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Review Dentistry, Oral Surgery & Medicine

Association between periodontitis and chronic kidney disease

Karo Parsegian et al.

Summary: Periodontitis and chronic kidney disease are chronic conditions with shared risk factors, but the exact relationship between them remains debated. Improving oral hygiene and periodontal treatment may reduce the risk of developing chronic kidney disease, highlighting the importance of interprofessional collaboration in managing these conditions.

PERIODONTOLOGY 2000 (2022)

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Article Biochemistry & Molecular Biology

Mechanisms of vascular damage by systemic dissemination of the oral pathogenPorphyromonas gingivalis

Cher Farrugia et al.

Summary: Studies have shown a clear association between periodontal disease and increased risk of cardiovascular disease. Pg directly mediates vascular damage by degrading PECAM-1 and VE-cadherin, providing a potential molecular mechanism for the contribution of Pg to cardiovascular disease.

FEBS JOURNAL (2021)

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Review Dentistry, Oral Surgery & Medicine

Subgingival fungi, Archaea, and viruses under the omics loupe

Patricia I. Diaz

Summary: The gingival crevice microbial communities responsible for periodontal diseases are not only composed of bacteria, but also contain fungi, Archaea, and viruses, which play potential roles in dysbiosis. Despite advancements in omics approaches, the characterization of nonbacterial components in subgingival microbiome is still limited, requiring further research to understand their ecological roles and contributions to disease processes.

PERIODONTOLOGY 2000 (2021)

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Review Dentistry, Oral Surgery & Medicine

Impact of systemic factors in shaping the periodontal microbiome

Flavia Teles et al.

Summary: Next-generation sequencing platforms have opened up new opportunities for studying oral microbiology in relation to oral and systemic health. These platforms have allowed for large-scale surveys of oral microbes, as well as exploration of the impact of systemic factors on the periodontal microbiome, including diseases, conditions, ethnicity, and genetics. The findings highlight the importance of understanding the systemic factors that shape the periodontal microbiome for patient management and treatment.

PERIODONTOLOGY 2000 (2021)

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Review Dentistry, Oral Surgery & Medicine

Host Modulation and Treatment of Periodontal Disease

M. G. Balta et al.

Summary: Periodontitis is the sixth-most prevalent disease in the world and the leading cause of tooth loss in adults. Recent studies have shown that synthetic and biological disease-modifying antirheumatic drugs, such as rituximab and tocilizumab, can improve periodontal clinical parameters. Probiotics and nutritional supplements have also been found to provide anti-inflammatory benefits in the treatment of periodontitis.

JOURNAL OF DENTAL RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity

Drake Winslow Williams et al.

Summary: The oral mucosa is an understudied barrier tissue rich in antigens and commensals, susceptible to periodontitis. By compiling a single-cell transcriptome atlas, researchers identified inflammatory epithelial and stromal cell populations promoting antimicrobial defenses and neutrophil recruitment. Exaggerated stromal cell responsiveness was found to enhance neutrophil and leukocyte infiltration in periodontitis, highlighting the role of tissue stroma in regulating mucosal tissue homeostasis and disease pathogenesis.

CELL (2021)

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Article Virology

Redondovirus Diversity and Evolution on Global, Individual, and Molecular Scales

Louis J. Taylor et al.

Summary: Redondoviridae is a newly established family of circular Rep-encoding single stranded DNA viruses that are widely distributed in the human respiratory tract. Studies have found that the virus has a high prevalence in saliva samples from rural African populations and urban U.S. populations, with diverse strains within individuals and evolving through recombination.

JOURNAL OF VIROLOGY (2021)

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Review Immunology

C3-targeted therapy in periodontal disease: moving closer to the clinic

George Hajishengallis et al.

Summary: Complement has a crucial role in periodontal disease, and targeting its central component C3 provides therapeutic benefits, potentially representing a novel approach for treating periodontitis.

TRENDS IN IMMUNOLOGY (2021)

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Article Medicine, Research & Experimental

Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation

Hatice Hasturk et al.

Summary: The study evaluated the efficacy and safety of a complement 3-targeted therapeutic, AMY-101, for gingival inflammation in adult patients. Results showed that AMY-101 significantly reduced gingival inflammation and the effects persisted for at least 3 months.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Review Immunology

Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities

George Hajishengallis et al.

Summary: Periodontitis is causally linked to the development of other chronic inflammatory diseases outside the oral mucosa, and intervention studies have shown that local treatment of periodontitis can ameliorate surrogate markers of comorbid conditions. Experimental animal studies have further strengthened the potential causal link by establishing biologically plausible and clinically consistent mechanisms. Understanding the impact of disseminated periodontal pathogens and systemic inflammation associated with periodontitis on extra-oral pathologies may lead to new therapeutic options to reduce the risk of periodontitis-associated comorbidities.

NATURE REVIEWS IMMUNOLOGY (2021)

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Review Dentistry, Oral Surgery & Medicine

Herpesvirus-bacteria synergistic interaction in periodontitis

Casey Chen et al.

PERIODONTOLOGY 2000 (2020)

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Review Dentistry, Oral Surgery & Medicine

Oral-lung microbiome interactions in lung diseases

Manoj J. Mammen et al.

PERIODONTOLOGY 2000 (2020)

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Review Dentistry, Oral Surgery & Medicine

Mechanisms underlying the association between periodontitis and atherosclerotic disease

Harvey A. Schenkein et al.

PERIODONTOLOGY 2000 (2020)

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Review Dentistry, Oral Surgery & Medicine

Clinical and public health implications of periodontal and systemic diseases: An overview

Robert J. Genco et al.

PERIODONTOLOGY 2000 (2020)

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Article Biochemistry & Molecular Biology

The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis

Sho Kitamoto et al.

CELL (2020)

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Editorial Material Dentistry, Oral Surgery & Medicine

Life-threatening pathogens in severe/progressive periodontitis: Focal infection risk, future periodontal practice, role of the Periodontology 2000

Jorgen Slots

PERIODONTOLOGY 2000 (2020)

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Review Dentistry, Oral Surgery & Medicine

Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy

George Hajishengallis et al.

PERIODONTOLOGY 2000 (2020)

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Oral diseases: a global public health challenge

Marco A. Peres et al.

LANCET (2019)

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Review Immunology

Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation

Triantafyllos Chavakis et al.

NATURE IMMUNOLOGY (2019)

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Article Dentistry, Oral Surgery & Medicine

Global-, Regional-, and Country-Level Economic Impacts of Dental Diseases in 2015

A. J. Righolt et al.

JOURNAL OF DENTAL RESEARCH (2018)

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Article Gastroenterology & Hepatology

Periodontal therapy favorably modulates the oral-gut-hepatic axis in cirrhosis

Jasmohan S. Bajaj et al.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2018)

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Article Medicine, General & Internal

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Spencer L. G. James et al.

LANCET (2018)

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The oral microbiota: dynamic communities and host interactions

Richard J. Lamont et al.

NATURE REVIEWS MICROBIOLOGY (2018)

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Article Endocrinology & Metabolism

Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial

Francesco D'Aiuto et al.

LANCET DIABETES & ENDOCRINOLOGY (2018)

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Global epidemiology of dental caries and severe periodontitis - a comprehensive review

Jo E. Frencken et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2017)

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Article Dentistry, Oral Surgery & Medicine

Impact of the global burden of periodontal diseases on health, nutrition and wellbeing of mankind: A call for global action

Maurizio S. Tonetti et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2017)

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Article Dentistry, Oral Surgery & Medicine

Effect of Non-Surgical Periodontal Treatment on Gingival Crevicular Fluid and Serum Endocan, Vascular Endothelial Growth Factor-A, and Tumor Necrosis Factor-Alpha Levels

Cigdem C. Turer et al.

JOURNAL OF PERIODONTOLOGY (2017)

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Review Rheumatology

The case for periodontitis in the pathogenesis of rheumatoid arthritis

Jan Potempa et al.

NATURE REVIEWS RHEUMATOLOGY (2017)

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Microbiota, cirrhosis, and the emerging oral-gut-liver axis

Chathur Acharya et al.

JCI INSIGHT (2017)

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Article Microbiology

Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity

E. Xiao et al.

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Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors from Immune Cell Attack

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IMMUNITY (2015)

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Article Public, Environmental & Occupational Health

Prevention of Healthcare-Associated Pneumonia with Oral Care in Individuals Without Mechanical Ventilation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Asako Kaneoka et al.

INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY (2015)

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Periodontitis: from microbial immune subversion to systemic inflammation

George Hajishengallis

NATURE REVIEWS IMMUNOLOGY (2015)

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Global Burden of Severe Periodontitis in 1990-2010: A Systematic Review and Metaregression

N. J. Kassebaum et al.

JOURNAL OF DENTAL RESEARCH (2014)

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Article Multidisciplinary Sciences

Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota

Kei Arimatsu et al.

SCIENTIFIC REPORTS (2014)

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Editorial Material Medicine, General & Internal

Time to take periodontitis seriously

Iain L. C. Chapple

BMJ-BRITISH MEDICAL JOURNAL (2014)

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Article Microbiology

Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin

Mara Roxana Rubinstein et al.

CELL HOST & MICROBE (2013)

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Article Dentistry, Oral Surgery & Medicine

Impact of periodontal disease and periodontal therapy on oral health-related quality of life

Fabian Brauchle et al.

INTERNATIONAL DENTAL JOURNAL (2013)

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Evidence that periodontal treatment improves biomarkers and CVD outcomes

Francesco D'Aiuto et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2013)

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Article Cardiac & Cardiovascular Systems

Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima-Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study

Moise Desvarieux et al.

JOURNAL OF THE AMERICAN HEART ASSOCIATION (2013)

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Article Dentistry, Oral Surgery & Medicine

Non-surgical periodontal therapy reduces coronary heart disease risk markers: a randomized controlled trial

Syed A. H. Bokhari et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2012)

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Article Dentistry, Oral Surgery & Medicine

Biological approaches to the development of novel periodontal therapies - Consensus of the Seventh European Workshop on Periodontology

Maurizio S. Tonetti et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2011)

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Review Dentistry, Oral Surgery & Medicine

Mechanisms involved in the association between peridontal diseases and cardiovascular disease

R. Teles et al.

ORAL DISEASES (2011)

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Article Dentistry, Oral Surgery & Medicine

Effect of Initial Periodontal Therapy on Oral Health-Related Quality of Life in Patients With Periodontitis in Japan

Atsushi Saito et al.

JOURNAL OF PERIODONTOLOGY (2010)

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Article Dentistry, Oral Surgery & Medicine

Periodontitis and risk for atherosclerosis: an update on intervention trials

Maurizio S. Tonetti

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Article Rheumatology

Control of periodontal infection reduces the severity of active rheumatoid arthritis

Mhd. Khaldoun Al-Katma et al.

JCR-JOURNAL OF CLINICAL RHEUMATOLOGY (2007)

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Treatment of periodontitis and endothelial function

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