Effects of simulated long-term exposure to bottled, neutral pH electrolyzed oxidizing water on the properties of denture base resins.

STATEMENT OF PROBLEM: Denture stomatitis can pose serious health risks, especially to older people. Chemical denture cleaning agents must be effective, yet not adversely affect the longevity of removable dentures. Ready-to-use (RTU) neutral pH electrolyzed oxidizing water (EOW) is an effective biocide against Candida albicans biofilms on denture resins, but the effects of daily disinfection with EOW on the physical and mechanical properties of resins have not been established. PURPOSE: The purpose of this in vitro study was to investigate the effects of simulated long-term exposure to RTU EOW on the color, surface characteristics, and flexural strength of denture base resins. MATERIAL AND METHODS: Heat-polymerized (HP), 3D printed (3D) and computer-aided design and computer-aided manufacture (CAD-CAM)-milled (CC) denture resin specimens (square: 20×20×3.3 mm; beam: 64×10×3.3 mm) were immersed in tap water (TW), RTU EOW (Neutral Anolyte ANK; Envirolyte; EOW), or a commercial denture cleaning tablet solution (Polident 3-Minute; Glaxo SmithKline; PD), mimicking a 5-minute once daily disinfection routine performed up to 3.0 years. Color and surface roughness were recorded (n=3, squares), and changes in color (∆E00) and surface roughness (∆Ra) were calculated. Flexural strength (n=12, beams) and surface hardness (n=18, beams) were measured with a universal testing machine. The fractured surfaces of specimens were examined by scanning electron microscopy and energy dispersive spectroscopy. Data were assessed by performing the Shapiro-Wilk or D'Agostino and Pearson normality tests. Two-way ANOVA or the Kruskal-Wallis test with a post hoc Tukey HSD or Dunn multiple comparisons (α=.05) was used for statistical analyses. RESULTS: No significant changes were found in either color or surface roughness for HP, 3D, and CC resins after 1.5-year and 3.0-year immersion in any of the agents (P>.05). The surface hardness of 3D resins reduced by 14% with TW and by 23% with EOW and PD at 3.0 years. The flexural strengths of all 3 resins were unaffected by 3.0-year immersion (P>.05). CONCLUSIONS: Simulated long-term immersion disinfection with RTU neutral pH EOW did not adversely affect the physical and mechanical properties of HP or CC denture resins.

Adaptive Nanoparticle-Mediated Modulation of Mitochondrial Homeostasis and Inflammation to Enhance Infected Bone Defect Healing.

Infected bone defects (IBDs) exhibit impaired healing due to excessive inflammation triggered by pathogen-associated molecular patterns (PAMPs) from bacteria. As a vital factor in orchestrating immune responses, mitochondrial homeostasis maintenance is central to inflammation blockade. This research developed a chameleon-like nanoplatform by covering hydroxyapatite nanoparticles with a cerium ion coordinated tannic acid supramolecular network (HA@Ce-TA), which adaptively functions to regulate mitochondrial homeostasis based on intra- and extracellular environments. Extracellularly, acidic conditions activate HA@Ce-TA's peroxidase/oxidase-mimicking activity to produce reactive oxygen species (ROS), and external near-infrared (NIR) irradiation excites nanoscale Ce-TA to produce hyperthermia, which is found and explained by chemical computation. ROS production with photothermal therapy can eliminate bacteria effectively and reduce mitochondrial stress. Intracellularly, HA@Ce-TA remodels mitochondrial dynamics by upregulating mitochondrial fusion genes and eliminates excessive ROS by mimicking superoxidase/catalase. Consequently, this comprehensive modulation of mitochondrial homeostasis inhibits inflammasome overactivation. In vitro and in vivo studies showed HA@Ce-TA can modulate the mitochondria-centered inflammatory cascade to enhance IBD treatment, highlighting the potential of engineering nanotherapeutics to recalibrate mitochondrial homeostasis as an infected disease-modifying intervention.

The genetic background determines material-induced bone formation through the macrophage-osteoclast axis.

Osteoinductive materials are characterized by their ability to induce bone formation in ectopic sites. Thus, osteoinductive materials hold promising potential for repairing bone defects. However, the mechanism of material-induced bone formation remains unknown, which limits the design of highly potent osteoinductive materials. Here, we demonstrated a genetic background link among macrophage polarization, osteoclastogenesis and material-induced bone formation. The intramuscular implantation of an osteoinductive material in FVB/NCrl (FVB) mice resulted in more M2 macrophages at week 1, more osteoclasts at week 2 and increased bone formation after week 4 compared with the results obtained in C57BL/6JOlaHsd (C57) mice. Similarly, in vitro, with a greater potential to form M2 macrophages, monocytes derived from FVB mice formed more osteoclasts than those derived from C57 mice. A transcriptomic analysis identified Csf1, Cxcr4 and Tgfbr2 as the main genes controlling macrophage-osteoclast coupling, which were further confirmed by related inhibitors. With such coupling, macrophage polarization and osteoclast formation of monocytes in vitro successfully predicted in vivo bone formation in four other mouse strains. Considering material-induced bone formation as an example of acquired heterotopic bone formation, the current findings shed a light on precision medicine for both bone regeneration and the treatment of pathological heterotopic bone formation.

Electrolysed oxidising water as a multi-purpose biocide in dental healthcare-A scoping review.

OBJECTIVES: The objective of this scoping review was to map evidence of electrolysed oxidising water (EOW) as a biocide for dental applications of relevance to older people and identify research gaps. BACKGROUND: EOW is an emerging, "green," and cost-effective biocide. There are no reviews on the landscape of EOW research as either an antiseptic or disinfectant in dental healthcare or its suitability for the oral healthcare of older people. MATERIALS AND METHODS: The review follows the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Database searches (Google Scholar, PubMed, Web of Science, Ovid, Scopus and Science Direct) were undertaken using MESH terms and Boolean operators with no date restrictions, to identify full-text, original reports published in English-language peer-reviewed journals. RESULTS: The search yielded 114 papers that met the inclusion/exclusion criteria. Dental applications of EOW include its use as an endodontic irrigant (39%); mouth rinse/surgical irrigant (21%); disinfectant for dental unit water lines (19%) and dental biomaterials (17%); and for antimicrobial efficacy, effects on oral tissues and on dental material properties. Most studies (83%) evaluated a single EOW formulation (acidic, moderately acidic or neutral) that was either generated at 'point-of-use' (POU; 72%), bottled ('ready-to-use', RTU; 24%) or from unspecified (3%) sources. Six reports evaluated storage-related parameters and 25 evaluated clinical applications; 89 were in vitro studies and one investigated the cost-effectiveness of POU EOW. CONCLUSIONS: Neutral-pH, EOW is effective as an antimicrobial agent without deleterious effects on oral tissues. However, research on the impact of storage conditions, anti-Candida biofilm efficacy and mechanism of action against yeasts, long-term effects on denture materials and cost-effectiveness is required to establish the suitability of EOW as a multipurpose biocide for dental healthcare, including infection-control requirements relating to older people.

Probiotic Escherichia coli Nissle 1917-derived outer membrane vesicles modulate the intestinal microbiome and host gut-liver metabolome in obese and diabetic mice.

Introduction: Obesity and diabetes are common chronic metabolic disorders which can cause an imbalance of the intestinal flora and gut-liver metabolism. Several studies have shown that probiotics, including Escherichia coli Nissle 1917 (EcN), promote microbial balance and metabolic health. However, there are no studies on how EcN outer membrane vesicles (EcN-OMVs) influence the intestinal microflora and affect the metabolic disorders of obesity and diabetes. Methods: In this study, we evaluated the effects of EcN-OMVs on high-fat diet (HFD)-induced obesity and HFD + streptozotocin (STZ)-induced diabetes. Results: EcN-OMVs could reduce body weight, decrease blood glucose, and increase plasma insulin in obese mice. Similarly, EcN-OMVs treatment could modify the ratio of Firmicutes/Bacteroidetes in the gut, elevate intestinal short-chain fatty acid (SCFA)-producing flora, and influence the SCFA content of the intestine. Furthermore, the intestinal metabolites ornithine and fumaric acid, hepatic ω-6 unsaturated fatty acids, and SCFAs were significantly increased after administering EcN-OMVs. Discussion: Overall, this study showed that EcN-OMVs might act as post-biotic agents that could modulate gut-liver metabolism and ameliorate the pathophysiology of obesity and diabetes.

Dual Photo-Enhanced Interpenetrating Network Hydrogel with Biophysical and Biochemical Signals for Infected Bone Defect Healing.

The healing of infected bone defects (IBD) is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, vascularization, and osteogenesis. Based on the theory that bone healing is regulated by both biochemical and biophysical signals, in this study, a copper doped bioglass (CuBGs)/methacryloyl-modified gelatin nanoparticle (MA-GNPs)/methacrylated silk fibroin (SilMA) hybrid hydrogel is developed to promote IBD healing. This hybrid hydrogel demonstrates a dual-photocrosslinked interpenetrating network mechanism, wherein the photocrosslinked SilMA as the main network ensures structural integrity, and the photocrosslinked MA-GNPs colloidal network increases strength and dissipates loading forces. In an IBD model, the hydrogel exhibits excellent biophysical characteristics, such as adhesion, adaptation to irregular defect shapes, and in situ physical reinforcement. At the same time, by sequentially releasing bioactive ions such as Cu2+ , Ca2+ , and Si2+ ions from CuBGs on demand, the hydrogel spatiotemporally coordinates antibacterial, immunomodulatory and bone remodeling events, efficiently removing infection and accelerating bone repair without the use of antibiotics or exogenous recombinant proteins. Therefore, the hybrid hydrogel can be used as a simple and effective method for the treatment of IBD.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

The effect of surface roughening of orthodontic elastomers on hydrophobicity and in vitro adherence of Streptococcus gordonii.

OBJECTIVES: Biofilm formation around orthodontic appliances causes gingivitis, enamel decalcification and caries. Bacteria adhere less readily to superhydrophobic surfaces. The aim of this study was to determine whether a superhydrophobic surface could be generated on orthodontic elastomers by surface modification in order to reduce bacterial adhesion. MATERIALS AND METHODS: Orthodontic elastomers were modified with sandpapers of various grit sizes (80-600 grit). Surface roughness of the modified and unmodified surfaces was assessed qualitatively with scanning electron microscopy and quantitatively with confocal microscopy. Water contact angles were measured with a goniometer to quantify hydrophobicity. Measurements were performed on unextended elastomers (100% original length) and elastomers extended to 150%, and 200% of the original length. Adhesion of Streptococcus gordonii to saliva coated elastomers was measured by counting colony forming units on agar plates. RESULTS: Abrasion with different sandpapers produced elastomers with surface roughness (Ra) ranging from 2 to 12 µm. Contact angles followed a quadratic trend with a maximum contact angle of 104° at an Ra of 7-9 µm. Average water contact angles, when viewed perpendicular to the direction of extension, decreased from 99° to 90° when the extension was increased from 100% to 200% and increased from 100° to 103° when viewed parallel to the direction of extension. Bacterial adhesion increased as roughness increased and this effect was more pronounced with elastomer extension. CONCLUSION: The surface roughness of orthodontic elastomers influences both their hydrophobicity and bacterial adhesion. Superhydrophobicity of elastomers could not be achieved with sandpaper abrasion.

The nano-windmill exerts superior anti-inflammatory effects via reducing choline uptake to inhibit macrophage activation.

Macrophages' activation plays a central role during the development and progression of inflammation, while the regulation of metabolic reprogramming of macrophages has been recently identified as a novel strategy for anti-inflammatory therapies. Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti-inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased slc44a1 expression in tFNA-treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR-slc44a1 is loaded into the tFNA to develop a new tFNA-based small interfering RNA (siRNA) delivery system named 'nano-windmill,' which exhibits a synergetic role by targeting slc44a1, finally blowing up the anti-inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti-inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA-based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti-inflammatory.

An All-in-One "4A Hydrogel": through First-Aid Hemostatic, Antibacterial, Antioxidant, and Angiogenic to Promoting Infected Wound Healing.

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu2+ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.

Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components.

The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour.

A Mechanically Reinforced Super Bone Glue Makes a Leap in Hard Tissue Strong Adhesion and Augmented Bone Regeneration.

Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting-edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L-DPZ) that integrates poly(vinyl alcohol), L-dopa amino acid, and zeolitic imidazolate framework-8 characterized by catechol-metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio-Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L-DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio-Oss and sustained osteogenesis of L-DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

Microbial Analysis of Obturators During Maxillofacial Prosthodontic Treatment Over an 8-Year Period.

The aim of the study was to investigate the microbial colonization (by Candida species, anaerobic and facultative anaerobic bacteria) of maxillary obturators used for the restoration of maxillary defects, including during radiotherapy.Retrospective cohort study.Fifteen patients requiring a maxillary obturator prosthesis had swabs of their obturators and adjacent tissues taken at different stages of their treatment over a period of 8 years.Identification of microbial species from the swabs was carried out using randomly amplified polymorphic DNA polymerase chain reaction (RAPD PCR) analysis, checkerboard DNA-DNA hybridization, CHROMagar Candida chromogenic agar, and DNA sequencing.Candida species were detected in all patients and all patients developed mucositis and candidiasis during radiotherapy which was associated with an increase in colonization of surfaces with Candida spp., particularly C albicans. Microbial colonization increased during radiotherapy and as an obturator aged, and decreased following a reline, delivery of a new prosthesis, or antifungal treatment during radiotherapy.Microbial colonization of maxillary obturators was related to the stage of treatment, age of the obturator material, radiotherapy and antifungal medications, and antifungal treatment may be recommended if C albicans colonization of palatal tissues is greater than 105 colony-forming units per cm2 following the first week of radiotherapy.

Adhesion of Yeast and Bacteria to Oral Surfaces.

Colonization of surfaces in the human body by microorganisms is an early, essential, step in the initiation of infectious disease. We have developed in vitro assays to investigate interactions between yeast or bacterial cells and human tissues, fluids, or prostheses. Such assays can be used to identify the adhesins, ligands, and receptors involved in these interactions, for example, by determining which components of the microbe or human tissue/fluid interfere with adherence in the assay. The assays can also be applied to find ways of preventing adhesion, and subsequent disease, by investigating the effects of different conditions and added compounds on adherence in the in vitro assays. Here we describe assays for measuring adhesion of the oral yeast Candida albicans, a common commensal and opportunistic pathogen, or the bacterium Staphylococcus epidermidis, which is not normally pathogenic but is known to form biofilms on medical prostheses. The assays described belong to two approaches to investigating adhesion and biofilm formation: (i) retention at a fixed time point following liquid washes, and (ii) retention against a continuous flow of medium.

The relationship between hair metabolites, air pollution exposure and gestational diabetes mellitus: A longitudinal study from pre-conception to third trimester.

Background: Gestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort. Methods: A total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution was estimated by two methods, namely proximal and land use regression (LUR) models, using air quality data from the air quality monitoring station nearest to the participant's home. Logistic regression and mixed models were applied to investigate associations between the air pollution exposure data and the GDM associated metabolites. Results: Of the 276 hair metabolites identified, the concentrations of fourteen were significantly different between GDM cases and non-GDM controls, including some amino acids and their derivatives, fatty acids, organic acids, and exogenous compounds. Three of the metabolites found in significantly lower concentrations in the hair of women with GDM (2-hydroxybutyric acid, citramalic acid, and myristic acid) were also negatively associated with daily average concentrations of PM2.5, PM10, SO2, NO2, CO and the exposure estimates of PM2.5 and NO2, and positively associated with O3. Conclusions: This study demonstrated that the maternal hair metabolome reflects the longitudinal metabolic changes that occur in response to environmental exposures and the development of GDM.

Investigating the impact of oral health on pregnancy and offspring outcomes: protocol for the Lifetime Impact of ORal heAlth (LIORA) cohort study.

INTRODUCTION: Oral health is a fundamental component of well-being, and is closely associated with overall health and quality of life. Oral health may also affect the next generation. The children of mothers with poor oral health are likely to also have poor oral health as they go through life. We aim to investigate associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health. METHODS AND ANALYSIS: The Lifetime Impact of Oral Health study is a prospective, observational cohort study being done at a single centre in Chongqing, China. A total of 1000 pregnant women will be recruited in their first trimester (11-14 weeks gestation). After obtaining informed consent, general and oral health assessments will be undertaken. Maternal lifestyle, demographic data and biospecimens (blood, hair, urine, nail clippings, saliva, dental plaque, buccal, vaginal and anal swabs) will be collected. Pregnancy outcomes will be recorded at the time of delivery. Cord blood and placenta samples will be collected. The offspring will be followed up for general and oral health examinations, neurodevelopmental assessments and biospecimen (dental plaque, saliva, buccal swabs, exfoliated primary dentition, urine, hair, nail clippings) collection until they are 15 years old. Biological samples will undergo comprehensive metabolomic, microbiome and epigenome analyses. Associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health will be investigated and the underlying mechanisms explored. ETHICS AND DISSEMINATION: This project has been approved by the Research Ethics Committee of the Affiliated Hospital of Stomatology of Chongqing Medical University (CQHS-REC-2021 LSNo.23). Participants will be required to provide informed consent to participate in the study. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100046898.

Nanocarrier-Assisted Delivery of Metformin Boosts Remodeling of Diabetic Periodontal Tissue via Cellular Exocytosis-Mediated Regulation of Endoplasmic Reticulum Homeostasis.

Endoplasmic reticulum (ER) dysfunction is a potential contributor to the impaired repair capacity of periodontal tissue in diabetes mellitus (DM) patients. Restoring ER homeostasis is thus critical for successful regenerative therapy of diabetic periodontal tissue. Recent studies have shown that metformin can modulate DM-induced ER dysfunction, yet its mechanism remains unclear. Herein, we show that high glucose elevates the intracellular miR-129-3p level due to exocytosis-mediated release failure and subsequently perturbs ER calcium homeostasis via downregulating transmembrane and coiled-coil domain 1 (TMCO1), an ER Ca2+ leak channel, in periodontal ligament stem cells (PDLSCs). This results in the degradation of RUNX2 via the ubiquitination-dependent pathway, in turn leading to impaired PDLSCs osteogenesis. Interestingly, metformin could upregulate P2X7R-mediated exosome release and decrease intracellular miR-129-3p accumulation, which restores ER homeostasis and thereby rescues the impaired PDLSCs. To further demonstrate the in vivo effect of metformin, a nanocarrier for sustained local delivery of metformin (Met@HALL) in periodontal tissue is developed. Our results demonstrate that compared to controls, Met@HALL with enhanced cytocompatibility and pro-osteogenic activity could boost the remodeling of diabetic periodontal tissue in rats. Collectively, our findings unravel a mechanism of metformin in restoring cellular ER homeostasis, enabling the development of a nanocarrier-mediated ER targeting strategy for remodeling diabetic periodontal tissue.

Voriconazole Treatment Induces a Conserved Sterol/Pleiotropic Drug Resistance Regulatory Network, including an Alternative Ergosterol Biosynthesis Pathway, in the Clinically Important FSSC Species, Fusarium keratoplasticum.

Fusarium keratoplasticum is the Fusarium species most commonly associated with human infections (fusariosis). Antifungal treatment of fusariosis is often hampered by limited treatment options due to resistance towards azole antifungals. The mechanisms of antifungal resistance and sterol biosynthesis in fusaria are poorly understood. Therefore, in this study we assessed the transcriptional response of F. keratoplasticum when exposed to voriconazole. Our results revealed a group of dramatically upregulated ergosterol biosynthesis gene duplicates, most notably erg6A (912-fold), cyp51A (52-fold) and ebp1 (20-fold), which are likely part of an alternative ergosterol biosynthesis salvage pathway. The presence of human cholesterol biosynthesis gene homologs in F. keratoplasticum (ebp1, dhcr7 and dhcr24_1, dhcr24_2 and dhcr24_3) suggests that additional sterol biosynthesis pathways may be induced in fusaria under other growth conditions or during host invasion. Voriconazole also induced the expression of a number of ABC efflux pumps. Further investigations suggested that the highly conserved master regulator of ergosterol biosynthesis, FkSR, and the pleiotropic drug resistance network that induces zinc-cluster transcription factor FkAtrR coordinate the response of FSSC species to azole antifungal exposure. In-depth genome mining also helped clarify the ergosterol biosynthesis pathways of moulds and provided a better understanding of antifungal drug resistance mechanisms in fusaria.

Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1.

BACKGROUND: The development of multidrug resistance (MDR) associated with the overexpression of the efflux transporters Mdr1 and Cdr1 in Candida species impedes antifungal therapies. The urgent need for novel agents able to inhibit the function of both pumps, led us to evaluate this property in 137 extracts obtained from Argentinian plants. METHODS: The ability of the extracts to reverse efflux pump-mediated MDR was determined with an agar chemosensitization assay using fluconazole (FCZ) resistant Mdr1- and Cdr1-overexpressing clinical isolates of Candida albicans and Candida glabrata as well as Saccharomyces cerevisiae strains selectively expressing Mdr1 (AD/CaMDR1) or Cdr1 (AD/CaCDR1). The resistance-reversing activity of the most potent extracts was further confirmed using a Nile Red accumulation assay. RESULTS: Fifteen plant extracts overcame the FCZ resistance of Candida albicans 1114, which overexpresses CaMdr1 and CaCdr1, and AD/CaMDR1, with those from Acalypha communis and Solanum atriplicifolium being the most effective showing 4- to 16-fold reversal of resistance at concentrations ≥ 25 µg/mL. Both extracts, and to a lesser extent that from Pterocaulon alopecuroides, also restored FCZ sensitivity in CgCdr1-overexpressing C. glabrata 109 and in AD/CaCDR1 with fold reversal values ranging from 4 to 32 and therefore demonstrating a dual effect against Mdr1 and Cdr1. Both, A. communis and S. atriplicifolium extracts at concentrations ≥ 12.5 and ≥ 25 µg/mL, respectively, increased the intracellular Nile Red accumulation in all yeast strains overexpressing efflux pumps. CONCLUSIONS: The non-toxic and highly active extracts from A. communis and S. atripicifolium, provide promising sources of compounds for potentiating the antifungal effect of FCZ by blocking the efflux function of Mdr1 and Cdr1 transporters.

Prevalence of halitosis among young adults in Dunedin, New Zealand.

OBJECTIVES: To investigate the prevalence of halitosis in young adults. METHODS: Young adults (n = 372; mean age = 21.0 ± 2.6 years old, range = 18-30 years) in Dunedin, New Zealand, were recruited into the cross sectional study after providing informed consent. The prevalence of halitosis was determined using both objective measurements (parts per billion [ppb] volatile sulphur compounds [VSCs] in the exhaled air) and subjective measurements (self-reported halitosis questionnaire, tongue coating index, and organoleptic assessment). RESULTS: Volatile sulphur compounds measurements indicated that the prevalence of halitosis (values ≥140 ppb) was 31.2%; 25.6% of participants self-reported halitosis. The organoleptic assessment revealed that 14.3% of the participants had a score of ≥2. A positive correlation was found between the VSC measurements and organoleptic assessment (p < 0.05). No significant relationship was found between self-reported halitosis and either organoleptic assessment or VSC measurements. Self-reported dry mouth, smoking, oral hygiene index, DMFT index, and tongue coating score were significantly associated with the organoleptic assessment (p < 0.05). The self-reported dry mouth, mouth breathing and tongue coating score were significantly associated with the VSC scores (p < 0.05). CONCLUSION: Halitosis, as represented by VSC, was found in 31.2% of the participants. VSC scores and organoleptic assessment were positively correlated. There was no significant relationship between self-reported halitosis and either organoleptic assessment or VSC measurements.