Medicine and Health Sciences Commons^™

Impaired Neutrophil Extracellular Trap-Forming Capacity Contributes To Susceptibility To Chronic Vaginitis In A Mouse Model Of Vulvovaginal Candidiasis, Junko Yano, Paul L. Fidel

School of Dentistry Faculty Publications

Vulvovaginal candidiasis (VVC), caused by is characterized by aberrant inflammation by polymorphonuclear neutrophils (PMNs) in the vaginal lumen. Data from the established murine model shows that despite potent antifungal properties, PMNs fail to clear due to local heparan sulfate that inhibits the interaction between PMNs and , resulting in chronic vaginal immunopathology. To understand the role of neutrophil extracellular traps (NETs) in defense against at the vaginal mucosa, we investigated the NET-forming capacity of PMNs in chronic VVC-susceptible (CVVC-S/C3H) and -resistant (CVVC-R/CD-1) mouse strains. Immunofluorescence revealed the formation of NETs (release of DNA with PMN-derived antimicrobial proteins) in PMN cocultures …

Cpg Odn/Mangiferin Dual Delivery Through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis And Promotes Alveolar Bone Regeneration In Mice., Yingzhi Gu, Yang Hu, Shengyuan Huang, Sunniva Ruiz, Toshihisa Kawai, Yuxing Bai, Xiaozhe Han

HPD Articles

The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with P. gingivalis-challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone …

The Role Of Nod-Like Receptors In Innate Immunity, Cassio Luiz Coutinho Almeida-Da-Silva, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

The innate immune system in vertebrates and invertebrates relies on conserved receptors and ligands, and pathways that can rapidly initiate the host response against microbial infection and other sources of stress and danger. Research into the family of NOD-like receptors (NLRs) has blossomed over the past two decades, with much being learned about the ligands and conditions that stimulate the NLRs and the outcomes of NLR activation in cells and animals. The NLRs play key roles in diverse functions, ranging from transcription of MHC molecules to initiation of inflammation. Some NLRs are activated directly by their ligands, while other ligands …

Interactions Between Silica And Titanium Nanoparticles And Oral And Gastrointestinal Epithelia: Consequences For Inflammatory Diseases And Cancer, Cassio Luiz Coutinho Almeida-Da-Silva, Leticia Ferreira Cabido, Wei Chun Chin, Ge Wang, David M. Ojcius, Changqing Li

All Dugoni School of Dentistry Faculty Articles

Engineered nanoparticles (NPs) composed of elements such as silica and titanium, smaller than 100 nm in diameter and their aggregates, are found in consumer products such as cosmetics, food, antimicrobials and drug delivery systems, and oral health products such as toothpaste and dental materials. They may also interact accidently with epithelial tissues in the intestines and oral cavity, where they can aggregate into larger particles and induce inflammation through pathways such as inflammasome activation. Persistent inflammation can lead to precancerous lesions. Both the particles and lesions are difficult to detect in biopsies, especially in clinical settings that screen large numbers …

Effects Of Frankincense Compounds On Infection, Inflammation, And Oral Health, Cassio Luiz Coutinho Almeida-Da-Silva, Nallusamy Sivakumar, Homer Asadi, Anna Chang-Chien, M. Walid Qoronfleh, David M. Ojcius, Musthafa Mohamed Essa

All Dugoni School of Dentistry Faculty Articles

Boswellia trees, found throughout the Middle East and parts of Africa and Asia, are the source of frankincense oil. Since antiquity, frankincense has been traded as a precious commodity, but it has also been used for the treatment of chronic disease, inflammation, oral health, and microbial infection. More recently, the bioactive components of Boswellia trees have been identified and characterized for their effects on cancer, microbial infection (especially infection by oral pathogens), and inflammation. Most studies have focused on cell lines, but more recent research has also investigated effects in animal models of disease. As natural products are considered to …

Oral Versus Gastrointestinal Mucosal Immune Niches In Homeostasis And Allostasis, Lina J Suárez, Silie Arboleda, Nikola Angelov, Roger M Arce

Journal Articles

Different body systems (epidermis, respiratory tract, cornea, oral cavity, and gastrointestinal tract) are in continuous direct contact with innocuous and/or potentially harmful external agents, exhibiting dynamic and highly selective interaction throughout the epithelia, which function as both a physical and chemical protective barrier. Resident immune cells in the epithelia are constantly challenged and must distinguish among antigens that must be either tolerated or those to which a response must be mounted for. When such a decision begins to take place in lymphoid foci and/or mucosa-associated lymphoid tissues, the epithelia network of immune surveillance actively dominates both oral and gastrointestinal compartments, …

Is There An Association Between Oral Health And Severity Of Covid-19 Complications?, Nathalie Botros, Parvati Iyer, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Most patients with severe complications from COVID-19 have underlying conditions such as obesity, diabetes, and hypertension. In parallel, there is growing evidence for a link between periodontitis and non-oral systemic diseases. The oral cavity is also a reservoir for respiratory pathogens, and patients with periodontal disease are more likely to develop hospital-acquired pneumonia than healthy individuals. We therefore hypothesize that improving oral health could decrease the severity of COVID-19 symptoms and reduce the associated morbidity.

Effect Of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium On Cerulein-Induced Acute Pancreatitis In Mice, Kamal Abdolmohammadi, Tayebeh Mahmoudi, Shahrzad Nojehdehi, Lobat Tayebi, Seyed Mahmoud Hashemi, Farshid Noorbakhsh, Alireza Abdollahi, Masoud Soleimani, Behrouz Nikbin, Mohammad Hossein Nicknam

School of Dentistry Faculty Research and Publications

Purpose: Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice.

Methods: AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). …

The Effect Of Smoking On Clinical Presentation And Expression Of Tlr-2 And Cd34 In Oral Lichen Planus Patients: Clinical And Immunohistochemical Study, Enji Ahmed, Nermin Raouf Amin, Nermin Youssif

Dentistry

Background: Oral lichen planus is a chronic inflammatory disease which is considered as a potential precancerous condition. Numerous studies have confirmed that inflammation is a strong risk factor for cancer development. Smoking is associated with potentially malignant disorders of the oral and oropharyngeal mucosa. The adverse consequences of smoking in various pathologies are mediated by its effects on the immune-inflammatory system. Little is known about the influence of cigarette smoke content on the course of OLP and inflammatory response. Methods: Twenty oral lichen planus smoker patients, 20 oral lichen planus non-smoker patients and 20 control patients were included in this …

Host Modulation And The Inflammatory Response, Carleigh Fraley, Jennifer Knox-Rodriguez, Diana V. Macri

Publications and Research

Host modulation therapy may be effective in controlling the immune response responsible for periodontal diseases.

Periodontal Inflammation: Integrating Genes And Dysbiosis, Shaoping Zhang, Ning Yu, Roger M Arce

Journal Articles

Biofilm bacteria co-evolve and reach a symbiosis with the host on the gingival surface. The disruption of the homeostatic relationship between plaque bacteria and the host can initiate and promote periodontal disease progression. Recent advances in sequencing technologies allow researchers to profile disease-associated microbial communities and quantify microbial metabolic activities and host transcriptional responses. In addition to confirming the findings from previous studies, new putative pathogens and novel genes that have not previously been associated with periodontitis, emerge. For example, multiple studies have reported that Synergistetes bacteria are associated with periodontitis. Genes involved in epithelial barrier defense were downregulated in …

Possible Role Of Tryptophan And Melatonin In Covid-19, Musthafa Mohamed Essa, Hamdan Hamdan, Saravana Babu Chidambaram, Buthainah Al-Balushi, Gilles J. Guillemin, David M. Ojcius, M. Walid Qoronfleh

All Dugoni School of Dentistry Faculty Articles

No abstract provided.

The Effect Of Smoking On Clinical Presentation And Expression Of Tlr-2 And Cd34 In Oral Lichen Planus Patients: Clinical And Immunohistochemical Study, Enji Ahmed Mahmoud, Nermin Yousif, Nermin Raouf

Dentistry

Background: Oral lichen planus is a chronic inflammatory disease which is considered as a potential precancerous condition. Numerous studies have confirmed that inflammation is a strong risk factor for cancer development. Smoking is associated with potentially malignant disorders of the oral and oropharyngeal mucosa. The adverse consequences of smoking in various pathologies are mediated by its effects on the immune-inflammatory system. Little is known about the influence of cigarette smoke content on the course of OLP and inflammatory response. Methods: Twenty oral lichen planus smoker patients, 20 oral lichen planus non-smoker patients and 20 control patients were included in this …

The Influence Of Vitamin D Supplementation On Local And Systemic Inflammatory Markers In Periodontitis Patients: A Pilot Study, Mohamed M Meghil, Lance Hutchens, Anas Raed, Neha A Multani, Mythilypriya Rajendran, Haidong Zhu, Stephen Looney, Mahmoud Elashiry, Roger M Arce, Mark E Peacock, Yanbin Dong, Christopher W Cutler

Journal Articles

OBJECTIVES: Vitamin D deficiency/insufficiency is a worldwide public health issue that has been linked to numerous inflammatory disorders, including periodontitis. There is increasing support for a role for adequate vitamin D levels in overall health. Populations with darker skin color have a higher prevalence of vitamin D deficiency/insufficiency and periodontitis. The purpose of this small pilot study was to investigate the influence of 12 weeks of 25(OH)D vitamin D supplementation (VDS) on mediators of systemic inflammation in dark-skinned, periodontitis patients.

MATERIALS AND METHODS: A total of 23 patients with moderate to severe periodontitis were randomly assigned to the vitamin D …

Ankylosing Spondylitis And Mesenchymal Stromal/Stem Cell Therapy: A New Therapeutic Approach, Kamal Abdolmohammadi, Fatemeh Dadgar Pakdel, Hamideh Aghaei, Sara Assadiasl, Yousef Fatahi, Negin Hosseini Rouzbahani, Alireza Rezaiemanesh, Masoud Soleimani, Lobat Tayebi, Mohammad Hossein Nicknam

School of Dentistry Faculty Research and Publications

Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, …

Nlrx1 Modulates Differentially Nlrp3 Inflammasome Activation And Nf-Κb Signaling During Fusobacterium Nucleatum Infection, Shu Chen Hung, Pei Rong Huang, Cassio Luiz Coutinho Almeida-Da-Silva, Kalina R. Atanasova, Ozlem Yilmaz, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). We found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, …

Lipoxin A4 Attenuates The Inflammatory Response In Stem Cells Of The Apical Papilla Via Alx/Fpr2, A. Gaudin, Miroslav Tolar, Ove A. Peters

All Dugoni School of Dentistry Faculty Articles

Similar to the onset phase of inflammation, its resolution is a process that unfolds in a manner that is coordinated and regulated by a panel of mediators. Lipoxin A4 (LXA₄) has been implicated as an anti-inflammatory, pro-resolving mediator. We hypothesized that LXA₄ attenuates or prevents an inflammatory response via the immunosuppressive activity of Stem Cells of the Apical Papilla (SCAP). Here, we report for the first time in vitro that in a SCAP population, lipoxin receptor ALX/FPR2 was constitutively expressed and upregulated after stimulation with lipopolysaccharide and/or TNF-α. Moreover, LXA₄ significantly enhanced proliferation, migration, and wound …

Immunohistochemical Expression Of Tlr-4 In Temporomandibular Joint Dysfunction, Luis Eduardo Almeida, Kyle Hresko, Adam Sorenson, Seth Butcher, Lobat Tayebi, Rosalia Leonardi, Carla Loreto, Jose A. Bosio, Flavio Camejo, Andrea Doetzer

School of Dentistry Faculty Research and Publications

Objective

Toll-like receptor 4 (TLR-4) is a transmembrane protein involved in the innate immune system and has been implicated in the pathogenesis of temporomandibular joint dysfunction (TMD). The purpose of this study was to histologically examine the level of expression of TLR-4 relative to severity of TMD.

Methods

Thirty-one human TMJ disc samples were immunostained for TLR-4 and evaluated for intensity of stain. Among the samples, 8 were control samples, 16 were from patients with anterior disc displacement with reduction (ADDwR), and 7 were from patients with anterior disc displacement without reduction (ADDwoR).

Results

There was no statistically significant difference …

Immunohistochemical Analysis Of Il-1 Receptor 1 In The Discs Of Patients With Temporomandibular Joint Dysfunction, Luis Eduardo Almeida, Adam Sorenson, Kyle Hresko, Seth Butcher, Rosalia Leonardi, Carla Lorento, Jose A. Bosio, Lobat Tayebi, Andrea Doetzer

School of Dentistry Faculty Research and Publications

Objective

Temporomandibular joint dysfunction (TMD) may affect a patient’s quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD.

Methods

Thirty-nine human disc samples were collected and composed three different groups: ADDwR (n = 19), ADDwoR ( …

Cross-Talk Between Clinical And Host-Response Parameters Of Periodontitis In Smokers, Radha Nagarajan, Craig S. Miller, Dolph R. Dawson Iii, Mohanad Al-Sabbagh, Jeffrey L. Ebersole

Institute for Biomedical Informatics Faculty Publications

Background and Objective

Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host‐response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens …

Biological Markers For Pulpal Inflammation: A Systematic Review., Dan-Krister Rechenberg, Johnah C. Galicia, Ove A. Peters

All Dugoni School of Dentistry Faculty Articles

BACKGROUND AND OBJECTIVE: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to …

Chemokine Function In Periodontal Disease And Oral Cavity Cancer, Sinem Esra Sahingur, W. Andrew Yeudall

Periodontics Publications

The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides with a wide range of activities that include recruitment of immune cells to sites of infection and inflammation, as well as stimulation of cell proliferation. As such, they function as antimicrobial molecules and play a central role in host defenses against pathogen challenge. However, their ability to recruit leukocytes and potentiate or prolong the inflammatory response may have profound implications for the progression of oral diseases such as chronic periodontitis, where tissue destruction may be widespread. Moreover, it is increasingly recognized that chronic inflammation is a key component of tumor …

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

All Dugoni School of Dentistry Faculty Articles

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …

Effects Of Aging On Apoptosis Gene Expression In Oral Mucosal Tissues, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = …