8 research outputs found
Interaction of poorphyromonas gingivalis protease (HRgpA) with epithelial cells
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Oral dysbiosis initiates periodontal disease in experimental kidney disease
No full textBackground and hypothesis: It is presently unclear why there is a high prevalence of periodontal disease in individuals living with chronic kidney disease. Whilst some have argued that periodontal disease causes chronic kidney disease, we hypothesized that alterations in saliva and the oral microenvironment in organisms with kidney disease may initiate periodontal disease by causing dysbiosis of the oral microbiota. Methods: Experimental kidney disease was created using adenine feeding and subtotal nephrectomy in rats, and by adenine feeding in mice. Loss of periodontal bone height was assessed using a dissecting microscope supported by micro-CT, light, confocal and electron microscopy, and immunohistochemistry. Salivary biochemistry was assessed using NMR spectroscopy. The oral microbiome was evaluated using culture-based and molecular methods, and the transmissibility of dysbiosis was assessed using co-caging and microbial transfer experiments into previously germ-free recipient mice. Results: We demonstrate that experimental kidney disease causes a reproducible reduction of alveolar bone height, without gingival inflammation or overt hyperparathyroidism but with evidence of failure of bone formation at the periodontal crest. We show that kidney disease alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from animals with kidney disease displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. Co-housing diseased rats with healthy ones ameliorates the periodontal disease phenotype, whilst transfer of oral microbiota from mice with kidney disease causes periodontal disease in germ-free animals with normal kidney function. Conclusions: We advocate that periodontal disease should be regarded as a complication of kidney disease, initiated by oral dysbiosis through mechanisms independent of overt inflammation or hyperparathyroidism.</p
Role of Side Chains in Charge Localization and Transfer in Azothiazol-Dithiophene Conjugated Copolymers
No full textCharge localization across conjugated polymers is one of the most important features to control their overall photophysical processes including the intermolecular charge transfer (CT) with molecular acceptors at interfaces. Herein, we synthesize two azothiazole (ATz) conjugated polymers coupled with a dithiophene (BT) donor using either esters or non-esters as side chains. The non-ester side chain polymer (P1ATz-BT) shows a strong emission quenching upon successful addition of 1,4-dicyanobenzene (DCB), as a molecular acceptor, via intermolecular CT. On the other hand, the ester side chain polymer (P2ATzE-BT) does not exhibit such changes, indicating that the side chain has a significant impact on the photophysical processes of these polymers at the interface with molecular acceptors. Density functional theory (DFT) calculations and time-resolved photoluminescence measurements show that unlike P1ATz-BT, the introduction of ester chains causes significant steric effects on the conformation of polymer backbones and the localization of electron density distributions in P2ATzE-BT, which leads to the suppression of the charge transfer to the molecular acceptor. Our study provides the experimental and theoretical clues for understanding the tremendous impact of polymer side chains on photophysical processes with molecular acceptors, at interfaces. These findings pave the way toward controlling and optimizing the interfacial charge transfers in conjugated polymers.The author would like to express their gratitude for the support provided by Jazan University, Kingdom of Saudi Arabia, and King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia. The author is also thankful to Dr. Zhen Zhang from the group of Professor Nikos Hadjichristidis, King Abdullah University of Science and Technology (KAUST), KAUST Catalysis Center, Polymer Synthesis Laboratory, Thuwal, Kingdom of Saudi Arabia, for synthesizing and providing the polymer samples
Effect of Donors on Intramolecular Photoinduced Charge-Transfer in π-Conjugated Donor-Acceptor Solutions for Solar Cells Applications.
No full textPhotoinduced charge transfer kinetics are essential in assessing the appropriateness of organic materials for solar cell applications. This study utilized femtosecond-to-microsecond time-resolved spectroscopy to examine the excited-state kinetics of a series of π-conjugated donor–acceptor polymers featuring the potent electron-withdrawing unit ((E)-1,2-di(thiazol-2-yl) diazene) (ATZ) alongside three distinct donor moieties: thieno [3,2-b] thiophene (TT), 2,2′-bithiophene (BT), and (E)-1,2-di(thiophen-2-yl) ethene (DTV). Steady-state absorption, fluorescence, density functional theory (DFT) calculations, and transient absorption (TA) spectroscopy were conducted to clarify their photophysical behavior in the presence of 1,4-dicyanobenzene (DCB), a recognized electron acceptor. The findings indicate that intramolecular charge transfer from the donor segments (TT, BT, and DTV) to DCB predominates the excited-state deactivation mechanisms. DFT studies reveal that the highest occupied molecular orbitals (HOMOs) are delocalized along the polymer backbone, whereas the lowest unoccupied molecular orbitals (LUMOs) are predominantly localized on the donor units, hence promoting efficient electron transfer to DCB. These findings elucidate the charge-transfer mechanisms of ATz-based donor–acceptor polymers and underscore their potential for solar applications.The author gratefully acknowledges the funding of the Deanship of Graduate Studies and Scientific Research, Jazan University, Saudi Arabia, through project number: (RG24-S060), and King Abdullah University of Science and Technology (KAUST) for facilitating the lab work
Horizontal and Vertical Transfer of Oral Microbial Dysbiosis and Periodontal Disease
No full textOne of the hallmark features of destructive periodontal disease, well documented over the last 50 y, is a change to the quantitative and qualitative composition of the associated microbiology. These alterations are now generally viewed as transformational shifts of the microbial populations associated with health leading to the emergence of bacterial species, which are only present in low abundance in health and a proportionate decrease in the abundance of others. The role of this dysbiosis of the health associated microbiota in the development of disease remains controversial: is this altered microbiology the driving agent of disease or merely a consequence of the altered environmental conditions that invariably accompany destructive disease? In this work, we aimed to address this controversy through controlled transmission experiments in the mouse in which a dysbiotic oral microbiome was transferred either horizontally or vertically into healthy recipient mice. The results of these murine studies demonstrate conclusively that natural transfer of the dysbiotic oral microbiome from a periodontally diseased individual into a healthy individual will lead to establishment of the dysbiotic community in the recipient and concomitant transmission of the disease phenotype. The inherent resilience of the dysbiotic microbial community structure in diseased animals was further demonstrated by analysis of the effects of antibiotic therapy on periodontally diseased mice. Although antibiotic treatment led to a reversal of dysbiosis of the oral microbiome, in terms of both microbial load and community structure, dysbiosis of the microbiome was reestablished following cessation of therapy. Collectively, these data suggest that an oral dysbiotic microbial community structure is stable to transfer and can act in a similar manner to a conventional transmissible infectious disease agent with concomitant effects on pathology. These findings have implications to our understanding of the role of microbial dysbiosis in the development and progression of human periodontal disease
Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3
No full textBecause there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp8–γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r−/− compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics
Low-Abundance Biofilm Species Orchestrates Inflammatory Periodontal Disease through the Commensal Microbiota and Complement
No full textSummaryPorphyromonas gingivalis is a low-abundance oral anaerobic bacterium implicated in periodontitis, a polymicrobial inflammatory disease, and the associated systemic conditions. However, the mechanism by which P. gingivalis contributes to inflammation and disease has remained elusive. Here we show that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss. The commensal microbiota and complement were both required for P. gingivalis-induced bone loss, as germ-free mice or conventionally raised C3a and C5a receptor-deficient mice did not develop bone loss after inoculation with P. gingivalis. These findings demonstrate that a single, low-abundance species can disrupt host-microbial homeostasis to cause inflammatory disease. The identification and targeting of similar low-abundance pathogens with community-wide impact may be important for treating inflammatory diseases of polymicrobial etiology
