Effect of Commercial Children's Mouthrinses and Toothpastes on the Viability of Neonatal Human Melanocytes: An In Vitro Study.

In this study, we examined the cytotoxic effects of six commercial children's mouthrinses (designated as #1, #2, #3, #4, #5, and #6) and four commercial children's toothpastes (designated as #1, #2, #3, and #4) on primary human neonatal melanocytes that were used as a representative model for oral melanocytes. Mouthrinses diluted directly with culture medium (1:2, 1:5, 1:10, 1:100, and 1:1000) were added to monolayers of melanocytes for 2 min, followed by 24 h recovery, after which MTS cytotoxicity assay was conducted. The extracts of each toothpaste were prepared (50% /), diluted in culture medium (1:2, 1:5, 1:10, 1:50, 1:100, and 1:1000), and added to cell monolayers for 2 min (standard brushing time), followed by an analysis of cell viability after 24 h.

A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization.

To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a "two-hit" model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); or both combined.

Efficacy of a Novel Pleiotropic MMP-Inhibitor, CMC2.24, in a Long-Term Diabetes Rat Model with Severe Hyperglycemia-Induced Oral Bone Loss.

Purpose: CMC2.24, a novel 4-(phenylaminocarbonyl)-chemically-modified-curcumin, is a pleiotropic MMP-Inhibitor of various inflammatory/collagenolytic diseases including periodontitis. This compound has demonstrated efficacy in host modulation therapy along with improved resolution of inflammation in various study models.

SAGE: Novel Therapy to Reduce Inflammation in a Naturally Occurring-Dog Model of Periodontal Disease.

Objective: To determine the effect of a semi-synthetic-glycosaminoglycan Ether (SAGE) as a universal therapeutic benefit to reduce periodontal inflammation and alveolar bone loss in naturally occurring-beagle-dog model of periodontal disease as a surrogate for human non-risk associated natural periodontitis.

Methods: Six adult female dogs with generalized periodontitis were distributed into two groups: control and SAGE treatment (n=3/group). After a 1-hour full-mouth scaling and root planning (SRP) at baseline, control or SAGE treatment (50mg/mL) bioadhesive gel formulation was locally applied for 12 weeks.

The Maximum-Tolerated Dose and Pharmacokinetics of a Novel Chemically Modified Curcumin in Rats.

Purpose: CMC 2.24, a chemically modified curcumin, was developed as a novel, pleiotropic MMP-inhibitor to treat various inflammatory/collagenolytic diseases including periodontitis. To date, this compound has shown efficacy in vitro, in cell culture, and in vivo (oral administration) in mice, rats and dogs.

A Novel Modified-Curcumin Promotes Resolvin-Like Activity and Reduces Bone Loss in Diabetes-Induced Experimental Periodontitis.

Purpose: Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a "bi-directional manner." However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis.

Therapeutic potential of a novel semi-synthetic-sulfated-polysaccharide to suppress inflammatory mediators in P. gingivalis LPS stimulated human monocytes/macrophages.

Background: Chronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. During chronic periodontitis, endotoxin (lipopolysaccharide, LPS) produced by P. gingivalis provokes monocyte accumulation and differentiation into macrophages and increased secretion of pro-inflammatory cytokines and matrix metalloproteases (MMPs).

Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic.

Introduction: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis.

Chemically-Modified Curcumin 2.24: A Novel Systemic Therapy for Natural Periodontitis in Dogs.

Purpose: To determine the effect of a pleiotropic MMP-inhibitor, a novel chemically-modified curcumin 2.24 (CMC2.24), on the clinical and biological measures of naturally-occurring periodontitis in the beagle dog.

Periodontal therapeutics: Current host-modulation agents and future directions.

With the recognition in the 1960s and 1970s of the periodontopathic importance of the microbial biofilm and its specific anaerobic microorganisms, periodontitis was treated as an infectious disease (more recently, as a dysbiosis). Subsequently, in the 1980s, host-response mechanisms were identified as the mediators of the destruction of the collagen-rich periodontal tissues (gingiva, periodontal ligament, alveolar bone), and the periodontopathogens were now regarded as the "trigger" of the inflammatory/collagenolytic response that characterizes actively destructive periodontitis. Also at this time a new pharmacologic strategy emerged, entitled "host-modulation therapy", based on 2 major findings: (1) that the ability of tetracycline antibiotics to inhibit periodontal breakdown was due (in large part) to their previously unrecognized ability to inhibit the host-derived matrix metalloproteinases (notably, the collagenases, gelatinases, macrophage metalloelastase), and by mechanisms unrelated to the antimicrobial properties of these medications; and (2) that nonsteroidal anti-inflammatory drugs, such as flurbiprofen, again by nonantimicrobial mechanisms, could reduce the severity of periodontitis (however, the adverse effects of long-term therapy precluded their development as safe and effective host-modulatory agents).

Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms.

The maxillofacial skeleton is highly dynamic and requires a constant equilibrium between the bone resorption and bone formation. The field of osteoimmunology explores the interactions between bone metabolism and the immune response, providing a context to study the complex cellular and molecular networks involved in oro-maxillofacial osteolytic diseases. In this review, we present a framework for understanding the potential mechanisms underlying the immuno-pathobiology in etiologically-diverse diseases that affect the oral and maxillofacial region and share bone destruction as their common clinical outcome.

Loss of alveolar bone density in postmenopausal, osteopenic women is associated with circulating levels of gelatinases.

Objective: To determine whether circulating levels of two matrix metalloproteinases, MMP-2 and MMP-9, are associated with loss of alveolar bone density (ABD) or height (ABH), or with progression of periodontitis (relative clinical attachment level [RCAL]), among postmenopausal women with local and systemic bone loss.

Background: This study was planned as part of a 2-year randomized, double-blind, placebo-controlled, clinical trial examining efficacy/safety of subantimicrobial dose doxycycline (20 mg bid) in postmenopausal osteopenic women. This study examines whether serum levels of gelatinases are associated with local changes in the periodontium.

Enhanced efficacy of chemically modified curcumin in experimental periodontitis: systemic implications.

Introduction: Dental microbial biofilm initiates gingival inflammation, and its suppression is the current dominant strategy for treating periodontitis. However, the host response to the biofilm is largely responsible for the connective tissue breakdown including alveolar bone loss, which is mediated by proinflammatory cytokines and matrix metalloproteinases (MMPs).

Methods: The current study compared the efficacy of a novel host-modulation compound, a chemically modified curcumin (CMC 2.

Differential effects of natural Curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis.

Objective: The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease.

Design: Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.

A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis.

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections.

A Novel Chemically Modified Curcumin "Normalizes" Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies.

Introduction. Impaired wound-healing in diabetics can lead to life-threatening complications, such as limb amputation, associated in part with excessive matrix metalloproteinase- (MMP-) mediated degradation of collagen and other matrix constituents. In the current study, a novel triketonic chemically modified curcumin, CMC2.

Impact of chemically-modified tetracycline 3 on intertwined physiological, biochemical, and inflammatory networks in porcine sepsis/ARDS.

Sepsis can lead to multiple organ dysfunction, including the Acute Respiratory Distress Syndrome (ARDS), due to intertwined, dynamic changes in inflammation and organ physiology. We have demonstrated the efficacy of Chemically-Modified Tetracycline 3 (CMT-3) at reducing inflammation and ameliorating pathophysiology in the setting of a clinically realistic porcine model of ARDS. Here, we sought to gain insights into the derangements that characterize sepsis/ARDS and the possible impact of CMT-3 thereon, by combined experimental and computational studies.

A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.

Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections.

4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation.

Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone.

Subantimicrobial-dose doxycycline treatment increases serum cholesterol efflux capacity from macrophages.

Objective: Subantimicrobial-dose doxycycline (SDD) treatment has been reported to reduce the severity of chronic inflammation and to increase serum high-density lipoprotein cholesterol. In a double-blind, placebo-controlled clinical trial, we determined whether SDD affects the ability of serum to facilitate cholesterol removal from macrophages.

Methods: Forty-five postmenopausal osteopenic women with periodontitis were randomly assigned to take placebo (n = 26) or doxycycline hyclate (20 mg, n = 19) tablets twice daily for 2 years.

Design, synthesis and biological activity of new polyenolic inhibitors of matrix metalloproteinases: a focus on chemically-modified curcumins.

Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components of the extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory and other diseases. Tetracyclines (TCs) are known inhibitors of mammalian-derived MMPs, and non-antibiotic formulations of Doxycycline are FDA-approved to treat periodontitis and the chronic inflammatory skin disease, rosacea. Because the C-11/ C-12 diketonic moiety of the tetracyclines is primarily responsible, through zinc-binding, for MMP inhibition, we have uniquely modified curcumin as a "core" molecule, since it contains a similar enolic system and is known to have beneficial effects in diseases where connective-tissue loss occurs.

Chemically modified tetracycline 3 prevents acute respiratory distress syndrome in a porcine model of sepsis + ischemia/reperfusion-induced lung injury.

Experimental pharmacotherapies for the acute respiratory distress syndrome (ARDS) have not met with success in the clinical realm. We hypothesized that chemically modified tetracycline 3 (CMT-3), an anti-inflammatory agent that blocks multiple proteases and cytokines, would prevent ARDS and injury in other organs in a clinically applicable, porcine model of inflammation-induced lung injury. Pigs (n = 15) were anesthetized and instrumented for monitoring.

Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: a mechanistic link between local and systemic inflammation.

Periodontitis, one of the most common chronic inflammatory diseases afflicting man, is increasingly being recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Non-antimicrobial tetracyclines are known to have inhibitory effects on inflammatory mediators and effector molecules, including cytokines and matrix metalloproteinases (MMPs), associated with both diseases. In this paper, we discuss the evidence that doxycycline and related non-antibiotic chemically modified tetracyclines (e.

Chemically modified tetracycline-3 (CMT-3): a novel inhibitor of the serine proteinase, elastase.

Two classes of enzymes play an important role in connective tissue breakdown during various inflammatory diseases: serine proteinases and matrix metalloproteinases (MMPs). Tetracyclines (TCs) exhibit important anti-inflammatory and MMP-inhibitory properties that are unrelated to their antibacterial activities. Of the various TCs and their chemically modified NON-antibiotic analogs (CMTs) tested in vitro and in vivo, CMT-3 (6-demethyl-6-deoxy 4 de-dimethylamino tetracycline) has repeatedly been shown to be the most potent inhibitor of MMP activity and cytokine production.

The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial.

Background: Periodontitis has been reported to be associated with coronary artery disease (CAD). Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases.

Methods: The study registrar randomly assigned 128 eligible postmenopausal women with chronic periodontitis to a twice-daily regimen of subantimicrobial-dose-doxycycline (SDD) or placebo tablets for two years as an adjunct to periodontal maintenance therapy.