Periodontal Pathogens and Neuropsychiatric Health

2020 ◽  
Vol 20 (15) ◽  
pp. 1353-1397 ◽  
Author(s):  
Abhishek Wadhawan ◽  
Mark A. Reynolds ◽  
Hina Makkar ◽  
Alison J. Scott ◽  
Eileen Potocki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Synergistic Interactions ◽  
Brain Vasculature ◽  
Micro Rnas ◽  
Clinical Conditions ◽  
Low Grade Inflammation ◽  
Neuropsychiatric Illness

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

The Inflammation Network in the Pathogenesis of Erectile Dysfunction: Attractive Potential Therapeutic Targets

2020 ◽  
Vol 26 (32) ◽  
pp. 3955-3972
Author(s):  
Ecem Kaya-Sezginer ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Metabolic Diseases ◽  
Inflammatory Marker ◽  
Attractive Potential ◽  
Common Denominator ◽  
Low Grade ◽  
Antiinflammatory Drugs ◽  
Male Population ◽  
Low Grade Inflammation

Background: Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, and diabetes. Objective: This review will present an overview of preclinical and clinical data regarding common inflammatory mechanisms involved in the pathogenesis of ED associated with metabolic diseases and the effect of antiinflammatory drugs on ED. Methods: A literature search of existing pre-clinical and clinical studies was performed on databases [Pubmed (MEDLINE), Scopus, and Embase] from January 2000 to October 2019. Results: Low-grade inflammation is a possible pathological role in endothelial dysfunction as a consequence of ED and other related metabolic diseases. Increased inflammation and endothelial/prothrombotic markers can be associated with the presence and degree of ED. Pharmacological therapy and modification of lifestyle and risk factors may have a significant role in the recovery of erectile response through reduction of inflammatory marker levels. Conclusion: Inflammation is the least common denominator in the pathology of ED and metabolic disorders. The inflammatory process of ED includes a shift in the complex interactions of cytokines, chemokines, and adhesion molecules. These data have established that anti-inflammatory agents could be used as a therapeutic opportunity in the prevention and treatment of ED. Further research on inflammation-related mechanisms underlying ED and the effect of therapeutic strategies aimed at reducing inflammation is required for a better understanding of the pathogenesis and successful management of ED.

Abstract 353: Chronic Polarization of Low-grade Inflammatory Monocytes During the Pathogenesis of Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Liwu Li ◽  
Shuo Geng
Keyword(s):  
High Fat Diet ◽  
Immunohistochemical Staining ◽  
Molecular Mechanisms ◽  
Molecular Switches ◽  
Low Grade ◽  
High Fat ◽  
Inflammatory Monocytes ◽  
Severe Atherosclerosis ◽  
Low Grade Inflammation ◽  
Deficient Mice

Background: Chronic inflammation mediated by low-grade inflammatory monocytes may serve as a key culprit for atherosclerosis. However, the cellular and molecular mechanisms responsible for the low-grade inflammatory polarization of monocytes are not well understood. We hypothesize that the selective clearance of homeostatic molecular switches may pre-dispose innate monocytes for the establishment of non-resolving low-grade inflammation. Methods and Results: By comparing high-fat-diet (HFD) fed ApoE deficient mice chronically challenged with either PBS or a subclinical dose endotoxin, we observed that subclinical endotoxin potently induced the establishment of low-grade inflammation, as manifested in elevated levels of systemic inflammatory mediators, accumulation of low-grade inflammatory circulating monocytes and neutrophils, as well as lipids. Immunohistochemical staining of liver and aorta tissues revealed significantly elevated steatosis and atherosclerosis in ApoE deficient mice chronically challenged with subclinical dose of endotoxin. At the mechanistic level, the polarization of low-grade inflammatory monocytes were due to the down-regulation and removal of key homeostatic molecules such as IRAK-M and Tollip. ApoE and IRAK-M double deficient mice had enhanced inflammatory polarization of innate monocytes, and developed severe atherosclerosis. Conclusions: Our data suggest that the clearance of homeostatic suppressors such as IRAK-M and Tollip may cause the memory establishment of low-grade inflammatory monocytes that are conducive for the chronic pathogenesis of atherosclerosis. Key words: Low-grade inflammation, monocyte polarization, innate memory, atherosclerosis

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

scholarly journals Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3356
Author(s):  
Lexie Harlan ◽  
London T. Mena ◽  
Latha Ramalingam ◽  
Shasika Jayarathne ◽  
Chwan-Li Shen ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Combined Treatment ◽  
Low Grade ◽  
Tart Cherry ◽  
Metabolic Complications ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Macrophage Inflammatory Protein

Chronic low-grade inflammation is a primary characteristic of obesity and can lead to other metabolic complications including insulin resistance and type 2 diabetes (T2D). Several anti-inflammatory dietary bioactives decrease inflammation that accompanies metabolic diseases. We are specifically interested in delta-tocotrienol, (DT3) an isomer of vitamin E, and tart cherry anthocyanins (TCA), both of which possess individual anti-inflammatory properties. We have previously demonstrated that DT3 and TCA, individually, reduced systemic and adipose tissue inflammation in rodent models of obesity. However, whether these compounds have combinatorial effects has not been determined yet. Hence, we hypothesize that a combined treatment of DT3 and TCA will have great effects in reducing inflammation in adipocytes, and that these effects are mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), a major inflammatory transcription factor. We used 3T3-L1 adipocytes and treated them with 1–5 µM doses of DT3 along with tart cherry containing 18–36 µg anthocyanin/mL, to assess effects on inflammation. Neither DT3 nor TCA, nor their combinations had toxic effects on adipocytes. Furthermore, pro-inflammatory markers interleukin-6 (IL-6) and p-65 (subunit of NFkB) were reduced at the protein level in media collected from adipocytes with both individual and combined treatments. Additionally, other downstream targets of NFkB including macrophage inflammatory protein 2 (Mip2), and Cyclooxygenase-2 (Cox2) were also significantly downregulated (p ≤ 0.05) when treated with individual and combined doses of DT3 and TCA with no additional combinatorial effects. In summary, DT3 and TCA individually, are beneficial in reducing inflammation with no additional combinatorial effects.

scholarly journals Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis

2019 ◽  
Author(s):  
L.C. Pessoa ◽  
G. Aleti ◽  
S. Choudhury ◽  
D. Nguyen ◽  
T. Yaskell ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Systemic Inflammation ◽  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Microbial Interactions ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Systemic Lupus ◽  
Periodontal Tissues ◽  
Low Grade Inflammation

AbstractSystemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche to assay local dynamic microbial ecological changes in health and disease important to systemic inflammation in SLE subjects. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiota on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy (n=31), SLE-inactive (n=29), and SLE-active (n=31). Patients were screened for probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and classified with or without periodontal dysbiosis, periodontitis. Serum inflammatory cytokines were measured by human cytokine panel and subgingival biofilm was examined by DNA-DNA checkerboard. The results showed significant upregulation of proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject’s into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. While low-grade inflammation was found in SLE-I subjects, a potent anti-inflammatory cytokine, IL-10 was found to control clinical phenotypes. Out of twenty-four significant differential oral microbial abundances found in SLE, fourteen unique subgingival bacteria profiles were found to be elevated in SLE. Pathogens from periodontal disease sites (Treponema denticola and Tannerella forsythia) showed increase abundance in SLE-A subjects when compared to controls. Cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Deeper clinical attachment loss and periodontal pathogens were found in SLE subjects, especially on SLE-I, likely due to long-term chronic and low-grade inflammation. Altogether, local periodontal pathogen enrichment was positively associated with high systemic inflammatory profiles, relevant to the overall health and SLE disease pathogenesis.

scholarly journals MicroRNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 859 ◽  
Author(s):  
Jean-François Landrier ◽  
Adel Derghal ◽  
Lourdes Mounien
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Untranslated Regions ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Micro Rnas

Metabolic disorders are characterized by the inability to properly use and/or store energy. The burdens of metabolic disease, such as obesity or diabetes, are believed to arise through a complex interplay between genetics and epigenetics predisposition, environment and nutrition. Therefore, understanding the molecular mechanisms for the onset of metabolic disease will provide new insights for prevention and treatment. There is growing concern about the dysregulation of micro-RNAs (miRNAs) in metabolic diseases. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to untranslated regions and coding sequences of the target mRNAs. This review aims to provide recent data about the potential involvement of miRNAs in metabolic diseases, particularly obesity and type 2 diabetes.

Relationship between gut microbiota, gut hyperpermeability, and obesity

2020 ◽  
Vol 27 ◽  
Author(s):  
Amin Gasmi ◽  
Pavan Kumar Mujawdiya ◽  
Lyudmila Pivina ◽  
Alexandru Doşa ◽  
Yuliya Semenova ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Close Relation ◽  
Low Grade ◽  
Cytokine Levels ◽  
Inflammatory Bowel ◽  
Low Grade Inflammation ◽  
The Relationship

: Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.

scholarly journals Molecular Mechanisms Underpinning Microparticle-Mediated Cellular Injury in Cardiovascular Complications Associated with Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-23 ◽  
Author(s):  
Tarek Benameur ◽  
Aisha Osman ◽  
Aijaz Parray ◽  
Ali Ait Hssain ◽  
Shankar Munusamy ◽  
...  
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
High Plasma ◽  
Cardiovascular Complications ◽  
Low Grade ◽  
Cellular Injury ◽  
Metabolic Disturbances ◽  
Pathophysiological Role ◽  
Low Grade Inflammation

Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100–1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues. Of interest and because of their easy detection using a variety of techniques, circulating MPs were recognized as biomarkers for cell activation. MPs were also found to mediate critical actions in intercellular communication and transmitting biological messages by acting as paracrine vehicles. High plasma numbers of MPs were reported in many cardiovascular and metabolic disturbances that are closely associated with insulin resistance and low-grade inflammation and have been linked to adverse actions on cardiovascular function. This review highlights the involvement of MPs in cardiovascular complications associated with diabetes and discusses the molecular mechanisms that underpin the pathophysiological role of MPs in the onset and progression of cellular injury in diabetes.

scholarly journals Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors

2020 ◽  
Vol 17 (11) ◽  
pp. 4135 ◽  
Author(s):  
Denisa Margină ◽  
Anca Ungurianu ◽  
Carmen Purdel ◽  
Dimitris Tsoukalas ◽  
Evangelia Sarandi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dietary Habits ◽  
Metabolic Diseases ◽  
Inflammatory Marker ◽  
Real Life ◽  
Lifestyle Changes ◽  
Dietary Factors ◽  
Low Grade ◽  
Metabolic Markers ◽  
Iκb Kinase

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kβ (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.

scholarly journals Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2163
Author(s):  
Yetirajam Rajesh ◽  
Devanand Sarkar
Keyword(s):  
Adipose Tissue ◽  
Cancer Progression ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Metabolic Complications ◽  
Endocrine Organ ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms ◽  
Low Grade Inflammation ◽  
Excessive Accumulation

Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.

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