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

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases

Chronic Oral Infection with Porphyromonas gingivalis Accelerates Atheroma Formation by Shifting the Lipid Profile

BACKGROUND: Recent studies have suggested that periodontal disease increases the risk of atherothrombotic disease. Atherosclerosis has been characterized as a chronic inflammatory response to cholesterol deposition in the arteries. Although several studies have suggested that certain periodontopathic bacteria accelerate atherogenesis in apolipoprotein E-deficient mice, the mechanistic link between cholesterol accumulation and periodontal infection-induced inflammation is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We orally infected C57BL/6 and C57BL/6.KOR-Apoe(shl) (B6.Apoeshl) mice with Porphyromonas gingivalis, which is a representative periodontopathic bacterium, and evaluated atherogenesis, gene expression in the aorta and liver and systemic inflammatory and lipid profiles in the blood. Furthermore, the effect of lipopolysaccharide (LPS) from P. gingivalis on cholesterol transport and the related gene expression was examined in peritoneal macrophages. Alveolar bone resorption and elevation of systemic inflammatory responses were induced in both strains. Despite early changes in the expression of key genes involved in cholesterol turnover, such as liver X receptor and ATP-binding cassette A1, serum lipid profiles did not change with short-term infection. Long-term infection was associated with a reduction in serum high-density lipoprotein (HDL) cholesterol but not with the development of atherosclerotic lesions in wild-type mice. In B6.Apoeshl mice, long-term infection resulted in the elevation of very low-density lipoprotein (VLDL), LDL and total cholesterols in addition to the reduction of HDL cholesterol. This shift in the lipid profile was concomitant with a significant increase in atherosclerotic lesions. Stimulation with P. gingivalis LPS induced the change of cholesterol transport via targeting the expression of LDL receptor-related genes and resulted in the disturbance of regulatory mechanisms of the cholesterol level in macrophages. CONCLUSIONS/SIGNIFICANCE: Periodontal infection itself does not cause atherosclerosis, but it accelerates it by inducing systemic inflammation and deteriorating lipid metabolism, particularly when underlying hyperlidemia or susceptibility to hyperlipidemia exists, and it may contribute to the development of coronary heart disease

The similitude of indoor airflow in natural ventilation for a reduced-scale model: Investigation of nonisothermal flow fields by RANS simulation

Reduced-scale experiments and simulations are important approaches in natural ventilation research, and the similarity requirement is fundamental for generalising the flow characteristics obtained from reduced-to full-scale conditions. However, the similarity requirement of a nonisothermal natural ventilation flow in a reduced-scale model poses additional challenges because of the reduced approaching flow, which can potentially result in Reynolds dependence issues. This study investigated the Reynolds number (Re) independence of indoor airflow in natural ventilation under isothermal and nonisothermal conditions using computational fluid dynamics (CFD) with Reynolds-averaged Navier–Stokes. A wind tunnel experiment was first conducted to validate the accuracy of the CFD using a reduced-scale model. Indoor airflow fields characterised by the same Archimedes number (Ar) but with varying approaching wind velocities and temperatures were compared between the full-scale and 1/10 reduced-scale simulations. The dimensionless ventilation rate showed the least dependence on the Re number, while the temperature field was very sensitive to the Re number, especially in the near-wall region. However, the temperature field on the ventilation pathway is much less dependent on the Re number, the deviation of which is less than 10 % compared to the full-scale simulation. The temperature distribution in the reduced-scale simulation exhibits a thermal stratification pattern similar to that in the full-scale simulation

Al₂O₃ Thin Layer Formed inside Porous Membrane Using Spray Synthesis Method and Its Application

Aluminum oxide (Al2O3) films have been investigated for use in various applications, and numerous deposition techniques have been reported. The spray synthesis method has the advantage of forming a thin layer of crystal at low temperatures using the appropriate precursors. A precursor prepared by diluting Methylaluminoxane with N-methyl pyrrolidone was sprayed onto a porous membrane while varying conditions such as the substrate temperature, feeding speed, and spray amount. The solution penetrated the film during spray application, and the ultra-thin layers deposited on the side wall of the internal pores were observed using a cross-sectional transmission electron microscope (XTEM). The lattice image obtained using the TEM and the composition analysis conducted using a scanning TEM and an energy-dispersive X-ray spectroscope suggest that this thin layer is a layer of Al2O3. The formation of Al2O3 occurred at lower temperatures than in previous reports. This is a major advantage for applications with low-melting-point materials. The most suitable spraying conditions were determined based on the state of deposition on the surface and inside the membrane. These conditions were applied to a three-layer separator for lithium-ion batteries and their effect on thermal stability was investigated. Through heating experiments and XRD analysis, it was confirmed that the shrinkage and melting of the separator are suppressed by spraying. This process can be expected to have wide applications in low-melting-point materials such as polyolefin

Effect of <it>Porphyromonas gingivalis</it> infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

<p>Abstract</p> <p>Background</p> <p>Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9), which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL) cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether <it>Porphyromonas gingivalis,</it> a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models.</p> <p>Methods</p> <p>We infected C57BL/6 mice intraperitoneally with <it>Porphyromonas gingivalis</it>, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR) gene and protein expression, as well as liver X receptors (<it>Lxrs</it>), inducible degrader of the LDLR (<it>Idol</it>), and sterol regulatory element binding transcription factor (<it>Srebf</it>)<it>2</it> gene expression, were examined in the liver.</p> <p>Results</p> <p><it>P. gingivalis</it> infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the <it>Pcsk9</it>, <it>Ldlr</it>, and <it>Srebf2</it> genes was upregulated in the livers of the <it>P. gingivalis</it>-infected mice compared with the sham-infected mice. Although <it>Pcsk9</it> gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP)2 (human homologue of Srebf2), whereas <it>Srebf2</it> is negatively regulated by cholesterol, the elevated expression of <it>Srebf2</it> found in the infected mice is thought to be mediated by <it>P. gingivalis</it> infection.</p> <p>Conclusions</p> <p><it>P. gingivalis</it> infection upregulates PCSK9 production via upregulation of <it>Srebf2</it>, independent of cholesterol levels. Further studies are required to elucidate how infection regulates <it>Srebf2</it> expression and subsequently influences lipid metabolism.</p