Dynamics of the content of reactive oxygen species and the state of the glutathione system in the oral cavity during subchronic intoxication wuth the fungicide thiram and its antioxidant correction.

Thiram is a dithiocarbamate derivative, which is used as a fungicide for seed dressing and spraying during the vegetation period of plants, and also as an active vulcanization accelerator in the production of rubber-based rubber products. In this study the content of reactive oxygen species (ROS) and the state of the glutathione system have been investigated in the oral fluid and gum tissues of adult male Wistar rats treated with thiram for 28 days during its administration with food at a dose of 1/50 LD50. Thiram induced formation of ROS in the oral cavity; this was accompanied by an imbalance in the ratio of reduced and oxidized forms of glutathione due to a decrease in glutathione and an increase in its oxidized form as compared to the control. Thiram administration caused an increase in the activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione transferase, and glutathione reductase). However, the time-course of enzyme activation in the gum tissues and oral fluid varied in dependence on the time of exposure to thiram. In the oral fluid of thiram-treated rats changes in the antioxidant glutathione system appeared earlier. The standard diet did not allow the glutathione pool to be fully restored to physiological levels after cessation of thiram intake. The use of exogenous antioxidants resviratrol and an Echinacea purpurea extract led to the restoration of redox homeostasis in the oral cavity.

Comparison Of Efficacy Of Steroids Alone And Combination Of Steroids With Hyaluronidase On Mouth Opening In Oral Submucous Fibrosis Patients.

BACKGROUND: Eventually Oral submucous fibrosis causes pronounced stiffness and failure to open the mouth. Objectives are to determine compare the efficacy of intralesional steroids alone and combination of steroids with hyaluronidase on mouth opening in oral submucous fibrosis. METHODS: It was a prospective comparative cohort study. Total of 74 patients both male and female having history of pan chewing and limited mouth opening and burning sensations were included in the study. Informed consent was taken and divided into two groups. Patients of group 1 were managed with mixture of betamethasone 1 ml and hyaluronidase 1500 IU and patients of group 2 were treated with only steroid injection of betamethasone 1 ml given intralesional, both injections were given intralesional, by multiple puncture technique and once a week and continued for twelve weeks (3 months). And data compiled and analyzed in SPSS-20. RESULTS: The mean age of group 1 was 40.027±6.97 years, and mean age of Group 2 was 37.351±5.48 years. In both groups, the greatest number of cases aged from 31-59 years. Compared to females in both groups, the majority of patients were males. In 32 (86.4)% patients of group 1 showed efficacy compared with 18[43.2] patients in group 2 [p-0.000]. Conclusion: In this study Intralesional steroids with hyaluronidase injections are more efficient for opening the mouth in patients with oral sub-mucus fibrosis.

Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis.

Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.

The human microbiome encodes resistance to the antidiabetic drug acarbose.

The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose1,2, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases3, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.

Crossover Analysis of the Astringent, Antimicrobial, and Anti-inflammatory Effects of Illicium verum/Star Anise in the Oral Cavity.

INTRODUCTION: Illicium verum commonly known as star anise has been widely used in many Asian countries for pharmaceutical treatment for many diseases. The aim of the present study was to investigate the anti-inflammatory, astringent, and antimicrobial properties of an Illicium verum mouthwash. METHODS: The present double blinded randomized clinical trial was conducted on fifty subjects, divided into groups A and B. Illicium verum mouthwash (group A) and placebo (group B) were provided to subjects for 21 days; after 14 days, washout period mouthwashes were switched as per crossover design between groups for 21 days. The gingival index (GI), papillary bleeding index (PBI), and oral microbial count were recorded at each stage of study. RESULTS: The significant intragroup difference was observed, before crossover in group A and after crossover in group B for GI, PBI, and oral microbial count at different stages of study. On comparing both group A and group B at the first and second follow-up for GI, PBI, and oral microbial count, a statistically significant difference (p < 0.05) was observed. A statistically highly significant mean intergroup and intragroup difference was seen for all the clinical parameters at different stages of study. CONCLUSION: The study revealed that the Illicium verum/star anise has potent antibacterial, anti-inflammatory, and astringent properties.

Anthocyanin complex niosome gel accelerates oral wound healing: In vitro and clinical studies.

An anthocyanin complex (AC), composed of extracts of purple waxy corn and blue butterfly pea petals, and AC niosomes, bilayered vesicles of non-ionic surfactants, were compared in in vitro and clinical studies. Cultured fibroblasts subjected to a scratch wound were monitored for cell viability, cell migration, nuclear morphology and protein expression. Scratched cells showed accelerated wound healing activity, returning to normal 24 h after treatment with AC niosomes (0.002 mg/mL). Western blots and immunocytochemistry indicated upregulation of type I, III and IV collagens, fibronectin and laminins in AC niosome-treated scratched cells. A randomized block placebo-controlled double-blind clinical trial in 60 volunteers (18-60 years old) with oral wounds indicated that AC niosome gel accelerated wound closure, reduced pain due to the oral wounds and improved participants' quality of life more than AC gel, triamcinolone gel and placebo gel. These data are consistent with enhanced delivery of AC to fibroblasts by use of niosomes. AC niosomes activated fibroblasts within wounded regions and accelerated wound healing, indicating that AC niosomes have therapeutic potential.

Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes.

Shammah is a smokeless tobacco product often mixed with lime, ash, black pepper and flavorings. Exposure to shammah has been linked with dental diseases and oral squamous cell carcinoma. There is limited literature on the prevalence of shammah and its role in pathobiology of oral cancer. In this study, we developed a cellular model to understand the effect of chronic shammah exposure on oral keratinocytes. Chronic exposure to shammah resulted in increased proliferation and invasiveness of non-transformed oral keratinocytes. Quantitative proteomics of shammah treated cells compared to untreated cells led to quantification of 4712 proteins of which 402 were found to be significantly altered. In addition, phosphoproteomics analysis of shammah treated cells compared to untreated revealed hyperphosphorylation of 36 proteins and hypophosphorylation of 83 proteins (twofold, p-value ≤ 0.05). Bioinformatics analysis of significantly altered proteins showed enrichment of proteins involved in extracellular matrix interactions, necroptosis and peroxisome mediated fatty acid oxidation. Kinase-Substrate Enrichment Analysis showed significant increase in activity of kinases such as ROCK1, RAF1, PRKCE and HIPK2 in shammah treated cells. These results provide better understanding of how shammah transforms non-neoplastic cells and warrants additional studies that may assist in improved early diagnosis and treatment of shammah induced oral cancer.

Review of the Current Medical and Surgical Treatment Options for Microstomia in Patients With Scleroderma.

BACKGROUND: Most patients with scleroderma suffer from microstomia, which can have debilitating consequences on their quality of life. Unfortunately, treatment options remain limited. No specific guidelines exist; hence, microstomia remains a challenge to treat in this patient population. OBJECTIVE: This review aims to evaluate the different medical and surgical treatment modalities currently available for microstomia in patients with scleroderma and make recommendations for future research. MATERIALS AND METHODS: A search of PubMed, Ovid MEDLINE, and Ovid Embase was conducted to identify articles discussing the treatment of microstomia in scleroderma. Twenty articles discussing surgical therapy and one article discussing medical therapy were reviewed. RESULTS: Mostly because of a scarcity of high-level evidence, no individual therapy has documented long-term efficacy. Some treatments demonstrate positive results and warrant further research. CONCLUSION: Given the variability of results, specific recommendations for the treatment of microstomia in patients with scleroderma are difficult to establish. A multifaceted approach that includes surgical and medical therapy is likely the best option to improve oral aperture in this patient population. Surgical treatments such as neurotoxins, autologous fat grafting, and ultraviolet A1 phototherapy may hold the most potential for improvement.

Applications of Silver Nanoparticles in Dentistry: Advances and Technological Innovation.

Silver nanoparticles (AgNPs) have been successfully applied in several areas due to their significant antimicrobial activity against several microorganisms. In dentistry, AgNP can be applied in disinfection, prophylaxis, and prevention of infections in the oral cavity. In this work, the use of silver nanoparticles in dentistry and associated technological innovations was analyzed. The scientific literature was searched using PubMed and Scopus databases with descriptors related to the use of silver nanoparticles in dentistry, resulting in 90 open-access articles. The search for patents was restricted to the A61K code (International Patent Classification), using the same descriptors, resulting in 206 patents. The results found were ordered by dental specialties and demonstrated the incorporation of AgNPs in different areas of dentistry. In this context, the search for patents reaffirmed the growth of this technology and the dominance of the USA pharmaceutical industry over AgNPs product development. It could be concluded that nanotechnology is a promising area in dentistry with several applications.

Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression.

COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

Understanding the Basis of METH Mouth Using a Rodent Model of Methamphetamine Injection, Sugar Consumption, and Streptococcus mutans Infection.

"METH mouth" is a common consequence of chronic methamphetamine (METH) use, resulting in tooth decay and painful oral tissue inflammation that can progress to complete tooth loss. METH reduces the amount of saliva in the mouth, promoting bacterial growth, tooth decay, and oral tissue damage. This oral condition is worsened by METH users' compulsive behavior, including high rates of consumption of sugary drinks, recurrent tooth grinding, and a lack of frequent oral hygiene. Streptococcus mutans is a Gram-positive bacterium found in the oral cavity and associated with caries in humans. Hence, we developed a murine model of METH administration, sugar intake, and S. mutans infection to mimic METH mouth in humans and to investigate the impact of this drug on tooth colonization. We demonstrated that the combination of METH and sucrose stimulates S. mutans tooth adhesion, growth, and biofilm formation in vivo METH and sucrose increased the expression of S. mutans glycosyltransferases and lactic acid production. Moreover, METH contributes to the low environmental pH and S. mutans sucrose metabolism, providing a plausible mechanism for bacterium-mediated tooth decay. Daily oral rinse treatment with chlorhexidine significantly reduces tooth colonization in METH- and sucrose-treated mice. Furthermore, human saliva inhibits S. mutans colonization and biofilm formation after exposure to either sucrose or the combination of METH and sucrose. These findings suggest that METH might increase the risk of microbial dental disease in users, information that may help in the development of effective public health strategies to deal with this scourge in our society.IMPORTANCE "METH mouth" is characterized by severe tooth decay and gum disease, which often causes teeth to break or fall out. METH users are also prone to colonization by cariogenic bacteria such as Streptococcus mutans In addition, this oral condition is aggravated by METH users' compulsive behavior, including the consumption of beverages with high sugar content, recurrent tooth grinding, and a lack of frequent oral hygiene. We investigated the effects of METH and sugar consumption on S. mutans biofilm formation and tooth colonization. Using a murine model of METH administration, sucrose ingestion, and oral infection, we found that the combination of METH and sucrose increases S. mutans adhesion and biofilm formation on the teeth of C57BL/6 mice. However, daily chlorhexidine-based oral rinse treatment reduces S. mutans tooth colonization. Similarly, METH has been associated with dry mouth or hyposalivation in users. Hence, we assessed the impact of human saliva on biofilm formation and demonstrated that surface preconditioning with saliva substantially reduces S. mutans biofilm formation. Our results are significant because to our knowledge, this is the first basic science study focused on elucidating the fundamentals of METH mouth using a rodent model of prolonged drug injection and S. mutans oral infection. Our findings may have important translational implications for the development of treatments for the management of METH mouth and more effective preventive public health strategies that can be applied to provide effective dental care for METH users in prisons, drug treatment centers, and health clinics.

Antibacterial and antibiofilm activities of cinnamon essential oil nanoemulsion against multi-species oral biofilms.

Cinnamon essential oil (CEO) has antibacterial properties, but its ability to suppress the formation of multi-species oral biofilms has not been fully elucidated. This study evaluated the antibacterial and antibiofilm activities of cinnamon essential oil nanoemulsion (CEON) against oral biofilms formed using a microcosm biofilm model. The biofilms were formed on bovine enamel specimens over a 7-day period, during which all specimens were treated with one of three solutions: 5% CEON (n = 35), 0.5% cocamidopropyl betaine (n = 35), or 0.12% chlorhexidine gluconate (CHX; n = 35). Antibacterial and antibiofilm activities were determined by the red/green ratios (R/G values) of 7-day-old mature biofilms photographed with quantitative light-induced fluorescence-digital, the number of aciduric bacterial colony-forming units (CFUs) within each biofilm, and the absorbance of bacterial suspensions. One-way and repeated-measures analysis of variance were performed to compare differences among the three solutions. R/G values were lowest in the 0.12% CHX group, but not significantly differ from the 5% CEON group. The number of CFUs and absorbance were lowest in the 5% CEON group. This study showed that nanoemulsified CEO inhibited the maturation of multi-species oral biofilms and the growth of oral microorganisms in biofilms, including aciduric bacteria that cause dental caries.

Oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy.

Human immunodeficiency virus has plagued mankind since the 1980's when the first case was documented. Human immunodeficiency virus-induced immunocompromised state can lead to several systemic and local manifestations, which often culminates in mortality. Oral candidiasis was one of the most prevalent opportunistic infections noted in human immunodeficiency virus-infected patients. The advent of highly active antiretroviral therapy has led to a significant reduction in both the mortality and the morbidity of infected patients. The combined antiretroviral therapy has also led to a decrease in the incidence of opportunistic infections including oral candidiasis. Thus, the presence of well-established oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy could be considered as an indicator of potential treatment failure. The present manuscript aims to review the published literature assessing the effect of highly active antiretroviral therapy on the incidence of oral candidiasis in human immunodeficiency virus-infected patients.

Reviewing the oral pigmented lesions of human immunodeficiency virus with emphasis on the effect of highly active antiretroviral therapy.

Acquired immunodeficiency syndrome a disease with high mortality rates is caused by the well-known human immunodeficiency virus. The disease is characterized by several opportunistic infections owing to the decreased CD4 lymphocyte counts. Oral manifestations of human immunodeficiency virus are vital as they are one of the early manifestations of the disease. Also, they serve as prognostic markers as they correlate with the CD4 lymphocyte counts of the affected individuals. Human immunodeficiency virus is not only common in the adult population but also can affect pediatric patients through vertical transmission. The initial therapeutic strategy for the management of the virus was only the prevention of opportunistic infections. Later in the mid-1990s, antiretroviral therapy was introduced but there was no significant improvement in prognosis. After the advent of combination therapy or the use of three antiretroviral drugs also known as highly active antiretroviral therapy, there has been a marked reduction in human immunodeficiency virus-associated mortality rates. The highly active antiretroviral therapy has several effects on the oral manifestations of the human immunodeficiency virus. The present paper aims to review the oral pigmented lesions associated with human immunodeficiency virus with an emphasis on the effect of highly active antiretroviral therapy.

Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.

BACKGROUND: While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors. RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less abundant or site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the Human Microbiome Project), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features. CONCLUSIONS: Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs. Video abstract.

Durable Oral Biofilm Resistance of 3D-Printed Dental Base Polymers Containing Zwitterionic Materials.

Poly(methyl methacralyate) (PMMA) has long been used in dentistry as a base polymer for dentures, and it is recently being used for the 3D printing of dental materials. Despite its many advantages, its susceptibility to microbial colonization remains to be overcome. In this study, the interface between 3D-printed PMMA specimens and oral salivary biofilm was studied following the addition of zwitterionic materials, 2-methacryloyloxyethyl phosphorylcholine (MPC) or sulfobetaine methacrylate (SB). A significant reduction in bacterial and biofilm adhesions was observed following the addition of MPC or SB, owing to their protein-repellent properties, and there were no significant differences between the two test materials. Although the mechanical properties of the tested materials were degraded, the statistical value of the reduction was minimal and all the properties fulfilled the requirements set by the International Standard, ISO 20795-2. Additionally, both the test materials maintained their resistance to biofilm when subjected to hydrothermal fatigue, with no further deterioration of the mechanical properties. Thus, novel 3D-printable PMMA incorporated with MPC or SB shows durable oral salivary biofilm resistance with maintenance of the physical and mechanical properties.

Lactoferrin and oral pathologies: a therapeutic treatment.

The oral cavity is a non-uniform, extraordinary environment characterized by mucosal, epithelial, abiotic surfaces and secretions as saliva. Aerobic and anaerobic commensal and pathogenic microorganisms colonize the tongue, teeth, jowl, gingiva, and periodontium. Commensals exert an important role in host defenses, while pathogenic microorganisms can nullify this protective function causing oral and systemic diseases. Every day, 750-1000 mL of saliva, containing several host defense constituents including lactoferrin (Lf), are secreted and swallowed. Lf is a multifunctional iron-chelating cationic glycoprotein of innate immunity. Depending on, or regardless of its iron-binding ability, Lf exerts bacteriostatic, bactericidal, antibiofilm, antioxidant, antiadhesive, anti-invasive, and anti-inflammatory activities. Here, we report the protective role of Lf in different oral pathologies, such as xerostomia, halitosis, alveolar or maxillary bone damage, gingivitis, periodontitis, and black stain. Unlike antibiotic therapy, which is ineffective against bacteria that are within a biofilm, adherent, or intracellular, the topical administration of Lf, through its simultaneous activity against microbial replication, biofilms, adhesion, and invasiveness, as well as inflammation, has been proven to be efficient in the treatment of all known oral pathologies without any adverse effects.

The Effect of Selected Dental Materials Used in Conservative Dentistry, Endodontics, Surgery, and Orthodontics as Well as during the Periodontal Treatment on the Redox Balance in the Oral Cavity.

Oxidative stress (OS) is a redox homeostasis disorder that results in oxidation of cell components and thus disturbs cell metabolism. OS is induced by numerous internal as well as external factors. According to recent studies, dental treatment may also be one of them. The aim of our work was to assess the effect of dental treatment on the redox balance of the oral cavity. We reviewed literature available in PubMed, Medline, and Scopus databases, including the results from 2010 to 2020. Publications were searched according to the keywords: oxidative stress and dental monomers; oxidative stress and amalgam; oxidative stress and periodontitis, oxidative stress and braces, oxidative stress and titanium; oxidative stress and dental implants, oxidative stress and endodontics treatment, oxidative stress and dental treatment; and oxidative stress and dental composite. It was found that dental treatment with the use of composites, amalgams, glass-ionomers, materials for root canal filling/rinsing, orthodontic braces (made of various metal alloys), titanium implants, or whitening agents can disturb oral redox homeostasis by affecting the antioxidant barrier and increasing oxidative damage to salivary proteins, lipids, and DNA. Abnormal saliva secretion/composition was also observed in dental patients in the course of OS. It is suggested that the addition of antioxidants to dental materials or antioxidant therapy applied during dental treatment could protect the patient against harmful effects of OS in the oral cavity.