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Arthritis Research & Therapy May 2024Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs)...
BACKGROUND
Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation.
METHODS
Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein.
RESULTS
Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1β release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge.
CONCLUSIONS
Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.
Topics: Animals; Uric Acid; Histone Deacetylases; Macrophages; Mice, Knockout; Gout; Mice; Mice, Inbred C57BL; Inflammation; Male; Arthritis, Gouty; Disease Models, Animal; Signal Transduction; Acrylamides; Phenylenediamines
PubMed: 38711064
DOI: 10.1186/s13075-024-03335-4 -
Contemporary Clinical Dentistry 2024Silver diamine fluoride (SDF) is a topical treatment for carious lesions and a primary preventative for newly exposed high-risk surfaces such as fissures and roots in...
INTRODUCTION
Silver diamine fluoride (SDF) is a topical treatment for carious lesions and a primary preventative for newly exposed high-risk surfaces such as fissures and roots in the first molars. Using potassium iodide (KI) after applying SDF has been recommended as a way of reducing the severity of black staining, as well as preserving its antibacterial effect useful in deep caries.
OBJECTIVE
The objective of this research was to compare the antibacterial effect of SDF, with and without KI, on (. ) and dental biofilm.
METHODS
The antibacterial effects of SDF, KI, and the combination of both were measured using three different techniques (inhibition halo, minimum inhibitory effect [MIE], and colony-forming unit [CFU], testing).
RESULTS
The results were then subjected to statistical analysis. Analyzed by means of the Kruskal-Wallis statistical test, the inhibition halos yielded a value of = 0.3309. Using the MIE test, only the SDF treatment produced an antibacterial effect, at 10%, compared to the KI group, with = 0.001. Finally, the CFU test revealed a total absence of colonies for all three reagents. All three substances analyzed achieved total inhibition of . . SDF is effective even in its minimal commercial concentration. Its antibacterial capacity decreases with the addition of KI.
CONCLUSIONS
The three substances analyzed at their maximum concentrations exhibited an antibacterial effect against . , resulting in total inhibition.
PubMed: 38707672
DOI: 10.4103/ccd.ccd_393_23 -
Scientific Reports May 2024Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group...
Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-25% of sporadic Parkinson's patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson's disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson's disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson's disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.
Topics: Humans; Parkinson Disease; Male; Biomarkers; Female; Aged; Middle Aged; Putrescine; Prospective Studies; Case-Control Studies
PubMed: 38693432
DOI: 10.1038/s41598-024-60872-3 -
Water Research Jun 2024Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous...
Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L) of metal ions, all the tested metal ions (Mg, Ca, Co, Pb, Ni, Cu, and Fe) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L). In contrast, EDTA (0.64 mg L) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.
Topics: Edetic Acid; Drug Resistance, Microbial; Gene Transfer, Horizontal; Plasmids; Metals, Heavy; Escherichia coli; Metals; Ions
PubMed: 38692255
DOI: 10.1016/j.watres.2024.121659 -
International Wound Journal May 2024The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic...
Assessment of the ability of Pseudomonas aeruginosa and Staphylococcus aureus to create biofilms during wound healing in a rat model treated with carboxymethyl cellulose/carboxymethyl chitosan hydrogel containing EDTA.
The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic acid (EDTA) as the materials for wound healing. CMC and CMCS solutions were prepared with a concentration of 4% (w/v). These solutions were made using normal saline serum with a concentration of 0.5% (v/v). Additionally, EDTA with the concentrations of 0.01%, 0.05%, 0.1%, 0.5%, 1%, and 2% (w/v) was included in the prepared polymer solution. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with average in size 88.71 ± 5.93 μm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. The antibacterial experiments showed that the formulated CMC/CMCS/EDTA 0.5% hydrogel inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, the produced hydrogels were haemocompatible and biocompatible. At the last stage, the evaluation of wound healing in the animal model demonstrated that the use of the produced hydrogels significantly improved the process of wound healing. Finally, the findings substantiated the effectiveness of the formulated hydrogels as the materials for promoting wound healing and antibacterial agents.
Topics: Animals; Chitosan; Rats; Edetic Acid; Staphylococcus aureus; Pseudomonas aeruginosa; Carboxymethylcellulose Sodium; Wound Healing; Biofilms; Hydrogels; Disease Models, Animal; Male; Anti-Bacterial Agents; Rats, Wistar; Staphylococcal Infections; Wound Infection; Pseudomonas Infections
PubMed: 38682897
DOI: 10.1111/iwj.14878 -
Cureus Mar 2024We aim to evaluate the bond strength between resin composite and primary demineralized dentin, pretreated with silver diamine fluoride (SDF) and simultaneous SDF with...
We aim to evaluate the bond strength between resin composite and primary demineralized dentin, pretreated with silver diamine fluoride (SDF) and simultaneous SDF with potassium iodide (KI) after thermal aging. In this in vitro study, human carious-free primary molars were randomly assigned into three groups and prepared by exposing the superficial dentin. The primary dentin of each molar was demineralized. The first group (the control) received saline treatment before bond application. SDF was pretreated for the second group, whereas SDF and KI were used for the third. After that, the pretreated dentin was immediately built with resin composite bonded with a universal adhesive and kept wet for 24 hours. Then, the pretreated molars were prepared into beam specimens for microtensile bond strength (µTBS), 16 for each group, and subjected to thermal aging. Lastly, they were tested using a universal testing machine, and the resulting data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. It was found that the SDF-KI group had a significant difference with both the control and SDF groups (p < 0.05), while the control and SDF groups showed no significant differences (p = 0.310). The SDF-KI group had the highest mean value of 11.73 ± 4.39 megapascal (MPa). In contrast, the control group had the lowest mean value of 9.31 ± 3.41 MPa. Post hoc pairwise comparison results showed that SDF-KI pretreatment had a significantly higher strength value than the control and SDF groups. Pretreatment of demineralized primary dentin with SDF-KI does not negatively affect the immediate loading of resin composite. However, under the limitation of this study, KI application after SDF pretreatment is recommended to enhance the bond's durability of resin composite to demineralized dentin.
PubMed: 38681260
DOI: 10.7759/cureus.57064 -
Journal of Dentistry Jun 2024Silver diamine fluoride (SDF) has gained popularity in dentistry as an anti-hypersensitive and anti-caries agent. This study aims to review the postoperative... (Review)
Review
OBJECTIVES
Silver diamine fluoride (SDF) has gained popularity in dentistry as an anti-hypersensitive and anti-caries agent. This study aims to review the postoperative instructions for SDF therapy and examine the evidence supporting these instructions in treating dentine hypersensitivity and caries control.
DATA AND SOURCES
Two independent reviewers searched three electronic databases (EMBASE, PubMed, and Web of Science) to identify clinical studies that used SDF to treat dentine hypersensitivity and dental caries. Additionally, they searched Google Chrome for information from manufacturers, the department of health, national dental organisations, authoritative dental organisations, and universities regarding SDF therapy for these conditions. Data on postoperative instructions were extracted, and their impact on the treatment of dentine hypersensitivity and caries control was investigated.
STUDY SELECTION
This review included 74 clinical studies, 11 sets of instructions from SDF manufacturers, and six recommendations from national dental organisations, departments of health and universities. Amongst the included records, 50 clinical studies, two manufacturers, and one department of health mentioned postoperative instructions for SDF therapy. The recommendations varied, from suggesting no specific instructions, immediate rinsing, refraining from eating or drinking for 30 to 60 min, and even avoiding brushing until the next day after SDF therapy. Notably, no clinical studies reported the effects of these postoperative instructions on the SDF treatment of dentine hypersensitivity or dental caries.
CONCLUSIONS
This scoping review highlights the presence of inconsistent postoperative instructions for SDF therapy in the treatment of dentine hypersensitivity and caries control. Furthermore, there is a lack of evidence supporting the effectiveness of these instructions.
CLINICAL SIGNIFICANCE
No evidence supports the postoperative instructions for SDF therapy for managing dentine hypersensitivity and dental caries. Studies are necessary to provide guidance for clinicians using SDF in their clinical practice.
Topics: Humans; Cariostatic Agents; Dental Caries; Dentin Desensitizing Agents; Dentin Sensitivity; Fluorides, Topical; Postoperative Care; Quaternary Ammonium Compounds; Silver Compounds
PubMed: 38679132
DOI: 10.1016/j.jdent.2024.105029 -
Journal of the American Dental... Jun 2024Silver diamine fluoride (SDF) gel was developed to overcome the clinical limitations of liquids with children. The authors conducted a clinical trial to determine caries... (Clinical Trial)
Clinical Trial
Using sequential applications of a novel silver diamine fluoride gel and sodium fluoride varnish to arrest severe early childhood caries lesions: A clinical trial with single group assignment.
BACKGROUND
Silver diamine fluoride (SDF) gel was developed to overcome the clinical limitations of liquids with children. The authors conducted a clinical trial to determine caries lesion arrest in primary teeth at 1-year follow-up when 38% SDF gel and 2.5% sodium fluoride varnish were applied sequentially at the same appointment. Parent satisfaction was assessed.
METHODS
The study design was an open-label prospective, clinical trial with single group assignment. Participants were 237 children aged 3 through 4 years at enrollment and from 5 centros educativos iniciales (preschools). Eligible children had 1 or more d3 (cavitation into dentin) active caries lesions. Teeth with active caries lesions (cavitation confined to enamel [d2] or d3) were treated by applying 1 or 2 drops of viscous 38% SDF gel (Advantage Silver Dental Arrest Gel, Elevate Oral Care, LLC) dabbing the excess with cotton. Treated teeth were covered with 2.5% sodium fluoride varnish (Fluorimax, Elevate Oral Care, LLC) to mask the taste. Treatment was repeated at 5 months postexamination. The primary outcome was caries lesion (d2-d3) arrest at 1 year.
RESULTS
Two hundred nineteen children were available at the 1-year follow-up. There was a median of 21 (interquartile range [IQR], 13-34) active carious surfaces (d2-d3) at baseline. Median arrested carious surfaces was 92.6% (IQR, 81.1%-100.0%; 95% CI, 86.8% to 95.2%). When parents were asked whether they were bothered by the color change of teeth, the median response on a 10-point scale in which 1 equaled not bothered at all and 10 equaled very bothered was 1.0 (IQR, 1.0-2.0).
CONCLUSIONS
Two applications of 38% SDF gel and 2.5% sodium fluoride varnish arrested greater than 90% of carious surfaces at 1 year and with high levels of parental satisfaction.
PRACTICAL IMPLICATIONS
Combined treatment was highly efficacious in a population with many caries lesions. This clinical trial was registered at ClinicalTrials.gov. The registration number is NCT05395065.
Topics: Humans; Silver Compounds; Fluorides, Topical; Dental Caries; Child, Preschool; Quaternary Ammonium Compounds; Cariostatic Agents; Prospective Studies; Female; Male; Sodium Fluoride; Gels; Treatment Outcome; Tooth, Deciduous; Follow-Up Studies; Patient Satisfaction
PubMed: 38678451
DOI: 10.1016/j.adaj.2024.02.013 -
Journal of Pharmacological Sciences Jun 2024Subretinal hemorrhages result in poor vision and visual field defects. During hemorrhage, several potentially toxic substances are released from iron-based hemoglobin...
Subretinal hemorrhages result in poor vision and visual field defects. During hemorrhage, several potentially toxic substances are released from iron-based hemoglobin and hemin, inducing cellular damage, the detailed mechanisms of which remain unknown. We examined the effects of excess intracellular iron on retinal pigment epithelial (RPE) cells. A Fe probe, SiRhoNox-1 was used to investigate Fe accumulation after treatment with hemoglobin or hemin in the human RPE cell line ARPE-19. We also evaluated the production of reactive oxygen species (ROS) and lipid peroxidation. Furthermore, the protective effect of-an iron chelator, 2,2'-bipyridyl (BP), and ferrostatin-1 (Fer-1) on the cell damage, was evaluated. Fe accumulation increased in the hemoglobin- or hemin-treated groups, as well as intracellular ROS production and lipid peroxidation. In contrast, BP treatment suppressed RPE cell death, ROS production, and lipid peroxidation. Pretreatment with Fer-1 ameliorated cell death in a concentration-dependent manner and suppressed ROS production and lipid peroxidation. Taken together, these findings indicate that hemoglobin and hemin, as well as subretinal hemorrhage, may induce RPE cell damage and visual dysfunction via intracellular iron accumulation.
Topics: Humans; Cell Death; Cell Line; Cyclohexylamines; Hemin; Hemoglobins; Iron; Iron Chelating Agents; Lipid Peroxidation; Phenylenediamines; Reactive Oxygen Species; Retinal Pigment Epithelium
PubMed: 38677785
DOI: 10.1016/j.jphs.2024.04.001 -
Environment International May 2024N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and... (Review)
Review
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and ozone exposure. This practice extends the lifespan of rubber products, including tires, by preventing cracking, aging, and deterioration. However, the environmental consequences of waste generated during rubber product use, particularly the formation of 6PPD-quinone (6PPD-Q) through the reaction of 6PPD with ozone, have raised significant concerns due to their detrimental effects on ecosystems. Extensive research has revealed the widespread occurrence of 6PPD and its derivate 6PPD-Q in various environmental compartments, including air, water, and soil. The emerging substance of 6PPD-Q has been shown to pose acute mortality and long-term hazards to aquatic and terrestrial organisms at concentrations below environmentally relevant levels. Studies have demonstrated toxic effects of 6PPD-Q on a range of organisms, including zebrafish, nematodes, and mammals. These effects include neurobehavioral changes, reproductive dysfunction, and digestive damage through various exposure pathways. Mechanistic insights suggest that mitochondrial stress, DNA adduct formation, and disruption of lipid metabolism contribute to the toxicity induced by 6PPD-Q. Recent findings of 6PPD-Q in human samples, such as blood, urine, and cerebrospinal fluid, underscore the importance of further research on the public health and toxicological implications of these compounds. The distribution, fate, biological effects, and underlying mechanisms of 6PPD-Q in the environment highlight the urgent need for additional research to understand and address the environmental and health impacts of these compounds.
Topics: Rubber; Animals; Phenylenediamines; Environmental Pollutants; Humans; Environmental Monitoring
PubMed: 38677083
DOI: 10.1016/j.envint.2024.108677