-
Journal of Endodontics Nov 2023Neutrophil extracellular traps (NETs) have been described as structures composed of DNA and proteins, such as elastase and myeloperoxidase, that are able to kill...
INTRODUCTION
Neutrophil extracellular traps (NETs) have been described as structures composed of DNA and proteins, such as elastase and myeloperoxidase, that are able to kill bacteria extracellularly. The aim of the present study was to evaluate the role of NETs in bone resorption observed in pulp infection-induced apical periodontitis in mice.
METHODS
Apical periodontitis was experimentally induced by exposing the dental pulp of the mandibular first molar of mice to the oral microenvironment. The expression of NETs was evaluated by immunofluorescence in mice and biopsies of apical periodontitis. Mice were treated with vehicle or DNase I to degrade NETs, and the samples were collected after 7 days. The size of the apical lesion and the osteoclast number were determined in hematoxylin-eosin- and tartrate-resistant acid phosphatase-stained sections, respectively. Osteoclast differentiation and function markers were evaluated by quantitative polymerase chain reaction. The level of NETs in the serum was determined by the myeloperoxidase-DNA PicoGreen assay.
RESULTS
We first confirmed the presence of neutrophils and NETs at the site of the lesion in mice and in biopsies of patients with apical periodontitis. The treatment of mice with DNase I reduced the level of NETs in the serum and led to a reduction in apical lesion size and alveolar bone resorption. This effect was associated with a reduction of local inflammatory infiltrate and a reduced number of osteoclasts. We found that the increased expression of Acp5, Ctsk, and Rankl genes associated with osteoclast formation and function were abrogated by the absence of NETs.
CONCLUSIONS
Our data highlight NETs as an important player in the pathogenesis of apical periodontitis with regard to the local inflammation and consequent bone resorption after pulp infection.
Topics: Periapical Periodontitis; Extracellular Traps; Animals; Osteoclasts; Mice; Neutrophils; Humans; Tartrate-Resistant Acid Phosphatase; Cathepsin K; Male; Alveolar Bone Loss; Deoxyribonuclease I; RANK Ligand
PubMed: 37619708
DOI: 10.1016/j.joen.2023.07.027 -
Cureus Nov 2023Adansonia digitata (Baobab) tree is an African tree with a long history in traditional medicine. The local inhabitants of Africa have been using the different tree... (Review)
Review
Adansonia digitata (Baobab) tree is an African tree with a long history in traditional medicine. The local inhabitants of Africa have been using the different tree components to treat medical diseases, such as fever, diarrhea, malaria, cough, dysentery, and microbial infections. Recently, the tree gained the attention of scientists due to its medical and pharmaceutical properties and nutritional values, which generated a myriad number of investigations regarding its phytochemical and macro- and micronutrient contents. The fruit pulp is especially rich in vitamin C, pectin, fibers, and minerals such as calcium, magnesium, potassium, phosphorus, zinc, iron, and copper. Additionally, the leaves contain high levels of calcium, while the seeds are considered a good source of protein and fat. Altogether, they contain a variety of polyphenols, fatty acids, and amino acids. The tree extracts possess potent antioxidant, cell-protective, and anti-inflammatory activities. However, no information was found in the literature about the use of Baobab tree products in the dental field. The aim of this review is to discuss the well-documented medical effects and chemical and mineral components of the different Baobab tree parts from a dental point of view to open more areas of research concerning its potential applications in the dental field. Antioxidants and vitamin C are known to help in maintaining healthy periodontal and gingival tissues. They also help in wound healing and alveolar bone integrity. Moreover, phytochemicals and phenolic compounds have been utilized in controlling dental plaque and manufacturing intracanal medications as they manifest antimicrobial and anti-inflammatory activities. Furthermore, calcium and phosphorus incorporation in dental biomaterials is commonly used in vital pulp therapy and repairing bone defects. After reviewing the reported medicinal and pharmaceutical activities of the Baobab tree, it can be inferred that the tree extracts possess potential uses in the dental field, which requires further investigation for validation.
PubMed: 38957190
DOI: 10.7759/cureus.49304 -
Angiology Jul 2023Red palms syndrome consists of an intense redness on the palms of the hands and, occasionally, the soles of the feet. This infrequent condition may be primary or... (Review)
Review
Red palms syndrome consists of an intense redness on the palms of the hands and, occasionally, the soles of the feet. This infrequent condition may be primary or secondary. The primary forms are either familial or sporadic. They are always benign and do not require treatment. The secondary forms may have a poor prognosis related to the underlying disease, for which early identification and treatment are imperative. Red fingers syndrome is also rare. It manifests as a persistent redness on the fingers or toes pulp. It is typically secondary either to infectious diseases like human immunodeficiency virus, hepatitis C virus and chronic hepatitis B or to Myeloproliferative Disorders, such as Thrombocythemia and Polycythemia vera. Manifestations spontaneously regress over months or years without trophic alterations. Treatment is limited to that of the underlying condition. Aspirin has been shown effective in Myeloproliferative Disorders.
PubMed: 37410889
DOI: 10.1177/00033197231185459 -
Journal of Veterinary Dentistry Sep 2023Microscopic alterations in the dental pulp of dogs have not been extensively studied. The aim of this study was to investigate microscopic alterations of the dental pulp...
Microscopic alterations in the dental pulp of dogs have not been extensively studied. The aim of this study was to investigate microscopic alterations of the dental pulp in dogs' teeth. One hundred and ten surgically extracted teeth (20 incisors, 23 canines, 28 premolars, and 39 molars) from 74 dogs, of different ages, with a history of chronic periodontitis (66 dogs), periapical abscesses (2 dogs), pulpitis (2 dogs), oral cavity neoplasms (2 dogs), dens invaginatus (1 dog), and dental fractures (1 dog) were included. Eight-one maxillary and 29 mandibular teeth were included. Coronal, radicular, and coronal plus radicular calculus were present in 28.2%, 17.3%, and 54.5% of the teeth, respectively. In total 78 teeth (71%) had pulp alterations, including fibrosis (26%), calcification (14%), necrosis associated with the absence of odontoblasts (14%), presence of predentin and dentin inside the cavity (8%), odontoblastic hyperplasia (3%), pigmentation (3%), pulpitis (2%), and pulp stones (1%). Forty-nine (60.5%) of the maxillary teeth and all of the mandibular teeth had pulp alterations. The premolars were most affected, and the molars least affected, by pulp alterations. Pulp fibrosis, calcification, and necrosis were observed in teeth irrespective of the distribution of dental calculus.
Topics: Dogs; Animals; Dental Pulp; Pulpitis; Necrosis; Dental Caries; Fibrosis; Dog Diseases
PubMed: 36814404
DOI: 10.1177/08987564231156507 -
Journal of the American Dental... Sep 2023A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of...
Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at...
BACKGROUND
A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years).
TYPES OF STUDIES REVIEWED
The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations.
RESULTS
The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children.
CONCLUSIONS AND PRACTICAL IMPLICATIONS
Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.
Topics: United States; Humans; Child; Acetaminophen; Acute Pain; American Dental Association; Oral Health; Toothache; Academies and Institutes; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37634915
DOI: 10.1016/j.adaj.2023.06.014 -
Bioactive Materials Jul 2024The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms...
The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.
PubMed: 38549772
DOI: 10.1016/j.bioactmat.2024.02.014 -
International Endodontic Journal Apr 2024To investigate novel diagnostic markers for pulpitis and validate by clinical samples from normal and inflamed pulp. To explore the relationship between diagnostic...
AIM
To investigate novel diagnostic markers for pulpitis and validate by clinical samples from normal and inflamed pulp. To explore the relationship between diagnostic markers and immune cells or their phenotypes during pulp inflammation.
METHODOLOGY
Two microarray datasets, GSE77459 and GSE92681, and identified differential expression genes were integrated. To understand immune features, gene functions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and ImmuneSigDB Gene Set Enrichment Analysis (GSEA) were analysed. For predictive purposes, machine learning techniques were applied to detect diagnostic markers. Immune infiltration in inflamed pulp was studied using CIBERSORT. The relationship between diagnostic markers and immune cells was investigated and validated their gene expression in clinical samples from the normal or inflamed pulp by qRT-PCR. Finally, the correlation between one marker, secreted phosphoprotein 1 (SPP1), encoding osteopontin (OPN), and dendritic cells (DCs)/macrophages was identified via HE staining and multiplex immunohistochemistry. An in vitro inflammatory dental pulp microenvironment model of THP-1 macrophages cocultured with dental pulp cells derived conditioned media (DPCs-CM) to investigate OPN production and macrophage phenotypes was established.
RESULTS
Analysis revealed unique immunologic features in inflamed pulp. Three diagnostic markers for pulpitis: endothelin-1 (EDN1), SPP1, and purine nucleoside phosphorylase (PNP), and validated them using qRT-PCR were predicted. Multiplex immunohistochemistry demonstrated OPN co-localized with activated DCs and M2 macrophages during pulp inflammation. In vitro experiments showed that THP-1 macrophages produced the highest levels of OPN when stimulated with DPCs-CM derived from the 20 μg/mL LPS pre-conditioned group, suggesting an M2b-like phenotype by increasing surface marker CD86 and expression of IL6, TNFα, IL10, and CCL1 but not CCL17 and MerTK. Levels of CCL1 and IL10 elevated significantly in the macrophages' supernatant from the 20 μg/mL LPS pre-conditioned CM group. OPN was proven co-localizing with CD86 in the inflamed pulp by immunofluorescence.
CONCLUSIONS
The current findings suggest that OPN can serve as a promising biomarker for pulpitis, correlated with DCs and macrophages. OPN macrophages in the inflamed pulp are associated with M2b-like phenotypes. These insights offer the potential for improved diagnosis and targeted therapy.
Topics: Humans; Pulpitis; Osteopontin; Interleukin-10; Lipopolysaccharides; Inflammation; Macrophages; Biomarkers; Gene Expression Profiling; Dendritic Cells; Dental Pulp
PubMed: 38279773
DOI: 10.1111/iej.14028 -
World Journal of Stem Cells Feb 2024Dental pulp stem/stromal cells (DPSCs) are fibroblast-like, neural crest-derived, and multipotent cells that can differentiate into several lineages. They are relatively...
Dental pulp stem/stromal cells (DPSCs) are fibroblast-like, neural crest-derived, and multipotent cells that can differentiate into several lineages. They are relatively easy to isolate from healthy and inflamed pulps, with little ethical concerns and can be successfully cryopreserved and thawed. The therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through and animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic diseases. Understanding that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans, several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs (hDPSCs) as a treatment modality for use in cell-based therapy, regenerative medicine/dentistry and tissue engineering. In clinical medicine, hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium (SHED-CM) repaired vascular damage of the corpus cavernous, which is the main cause of erectile dysfunction. Whereas in clinical dentistry, autologous SHED was able to regenerate necrotic dental pulp after implantation into injured teeth, and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony defects. In contrast, hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction sockets. Large-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.
PubMed: 38455102
DOI: 10.4252/wjsc.v16.i2.54 -
Brain Research Nov 2023Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognition decline and memory deterioration. The molecular pathogenic mechanism of...
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognition decline and memory deterioration. The molecular pathogenic mechanism of AD is highly complex and still not completely clarified. While stem cell-based therapy for AD has been considered an optimal choice with specific properties however, immune rejection and risk of malignant transformation limit their therapeutic application. Growing evidence suggest that mitochondrial dysfunction has a critical role in the progression of AD. Since there have not been any effective treatment for AD, the drugs targeted to mitochondria may hold a great promise Therefore, the major objective of this study is to evaluate the therapeutic applicability of transplanting MSCderived mitochondria as a neuroprotective biomolecule in Alzheimer's disease pathology. The hallmarks of AD i.e aggregation of Aβ protein and Tau protein were generated to mimic the AD like pathology in vitro. Further, morphology analysis, cell viability assay, and immunofluorescence assay have been done for validation. Mitochondria were isolated from dental pulp stem cell (DPSC) and their effect on internalization by neural cells was demonstrated by cell proliferation analysis and uptake studies while their therapeutic potential was characterized by morphology analysis, ROS study, and immunofluorescence analysis. We observed that internalization of DPSC-derived mitochondria led to significant neuroprotective in the cellular AD. Based on our results, it may be concluded that mesenchymal stem cellderived mitochondria can emerge as a potentially safe and effective modality in Alzheimer's disease.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; tau Proteins; Neurons; Mitochondria; Cognitive Dysfunction
PubMed: 37619852
DOI: 10.1016/j.brainres.2023.148544 -
Stem Cell Reviews and Reports Nov 2023Recent progress in exosome based studies has revealed that they possess several advantages over cells, including "cell-free" properties, low immunogenicity and ethical... (Review)
Review
Recent progress in exosome based studies has revealed that they possess several advantages over cells, including "cell-free" properties, low immunogenicity and ethical controversy, high biological safety and effective action. These characteristics confer exosomes significant advantages that allow them to overcome the limitations associated with traditional "cell therapy" by circumventing the issues of immune rejection, scarcity of donor cells, heterogeneity, and ethical concerns. Identification of a complete and effective radical treatment for irreversible pulpal disease, a common clinical problem, continues to pose challenges. Although traditional root canal therapy remains the primary clinical treatment, it does not fully restore the physiological functions of pulp. Although stem cell transplantation appears to be a relatively viable treatment strategy for pulp disease, issues such as cell heterogeneity and poor regeneration effects remain problematic. Dental pulp regeneration strategies based on "cell-free" exosome therapies explored by numerous studies appear to have shown significant advantages. In particular, exosomes derived from odontogenic stem cells have demonstrated considerable potential in tooth tissue regeneration engineering, and continue to exhibit superior therapeutic effects compared to non-odontogenic stem cell-derived exosomes. However, only a few studies have comprehensively summarised their research results, particularly regarding the critical factors involved in the process. Therefore, in this study, our purpose was to review the effects exerted by odontogenic exosomes on pulp regeneration and to analyse and discus crucial factors related to this process, thereby providing scholars with a feasible and manageable new concept with respect to regeneration schemes.
Topics: Dental Pulp; Exosomes; Regeneration; Cell- and Tissue-Based Therapy; Hematopoietic Stem Cell Transplantation
PubMed: 37578647
DOI: 10.1007/s12015-023-10597-z