Impact of diabetes mellitus on dental pulp tissue pathosis - A scoping review.

Multipotent stem cells are the most crucial factor in tissue engineered regeneration procedures. Although bone marrow has been most widely studied and used as mesenchymal stem cell (MSC) source, several attempts have recently been made to obtain multipotential stem cells from more easily accessible sources, including skin, fat, periosteum and dental tissues1-5. In previous studies, skin has been shown as an excellent adult stem cell source, which differentiated into osteogenic and neural cells in vitro and enhanced bone formation in the maxillary sinus floor and nerve regeneration in vivo5,6. Further, stem cells derived from fetus differentiated into primordial germ cell and oocyte, and exhibited similar characteristics compared to embryonic stem cells7,8. However, harvesting skin tissue also involves an invasive procedure, and stem cells from the skin of older donors possess less stemness and regenerative potential than that of younger donors4,5. Dental tissues from extracted teeth could be used as alternative sources of adult stem cells. Dental stem cells were firstly isolated from the pulp tissues of removed third molars (dental pulp stem cell, DPSC), and showed similar characteristics with bone marrow derived MSC1,2. After then, some researchers have succeeded in the isolation of stem cells from the pulp tissues of human exfoliated deciduous teeth (SHED)9 or mesiodens10. Subsequently, other dental tissues, such as periodontal ligament11, root apical papilla12, and tooth follicle13, have been explored as adult stem cell sources. MSC-like characteristics of dental stem cells with plastic adherent growth and colony formation, expression of MSC-specific cell surface markers, and multilineage in vitro differentiation ability were similar to those of MSCs from skin or bone marrow14. However, interestingly, different dental tissues from same donor showed varying stem cell characteristics, including transcription factor expression levels and in vitro differentiation potential15. Stem cells from root papilla showed the highest expression level of transcription factors and cell surface markers15. However, dental follicle derived cells showed enhanced osteoblast-specific genes and ectopic bone formation after in vivo transplantation14, indicating dental follicle is the powerful stem cell source in bone tissue regeneration. Dental pulp is expected to harbor the pools of undifferentiated precursor cells for nerve or vascular tissue regeneration. The most powerful advantage of dental tissues as stem cells source is that primitive and multipotent tissues could be obtained around age 20, a later age compared to that of other stem cell sources, such as umbilical cord blood or matrix. If these dental tissues are preserved for long time without losing their stemness, they could be used as autologous stem cell source for demanding applications in regenerative medicine. A recent study reported the successful isolation of stem cells from long-term cryopreserved dental pulp tissues of deciduous teeth using a cryoprotectant, 90% fetal bovine serum (FBS) and 10% dimethyl sulfoxide16. However, FBS is xenogenic material for human tissue and cells and may alter tissue's properties, and not suitable for long-term preservation of human tissues. Interestingly, an efficient and safe dental tissue cryopreservation method using sucrose and ethylene glycol has been developed, and further analyses are being proceeded for its clinical application (data not published). In near future, the dental tissues, follicle, pulp and root papilla, of extracted wisdom teeth could be cryopreserved for later use as autologous stem cells sources.

inhibiting T-helper cells while activating regulatory T-cells and suppressing B-lymphocytes 8,9 .This immunomodulatory effect of MSCs makes them suitable for treatment of severe autoimmune diseases and graft-versus-host disease 8 .However, most trials for the clinical application of MSCs have used bone marrow-derived MSCs (BMSCs).As mentioned previously, MSCs from dental tissue (DMSCs) exhibit similar characteristics to BMSCs, but have superior osteogenic differentiation potential 3,6 .Therefore, DMSCs could possibly replace BMSCs in cell therapy and tissue regeneration applications.The new cryopreservation method for dental tissue enables the use of autologous MSCs from preserved dental tissue of extracted wisdom teeth 7 .These autologous MSCs could reduce unexpected side effects during clinical use, while maintaining similar immunomodulatory efficacy.In conclusion, dental tissue from immature wisdom teeth, including that from the dental follicle, pulp, and root apical papilla, possesses abundant multipotent stem cells that could be useful in both cell therapy and tissue regeneration.Traditionally, these dental tissues have been discarded after extraction.In the future, dental tissue obtained via extraction of impacted teeth should be cryopreserved for use as an autologous stem cell source.The long-term preservation of dental tissue after tooth extraction could thus create a new business model in dentistry, as well as provide greater access to autologous MSCs for patients in need.

Immunohistochemical Analysis of S100 Proteins in Normal and Irreversibly Inflamed Human Dental Pulps

The Interactions Between Physicians and Dentists in Managing the Care of Patients With Diabetes Mellitus

The purpose of this study was to investigate the oxidative stress cycle consisting of reactive oxygen molecules (ROS), glutathione (GSH) and glutathione S-transferase (GST) in caries-related pulp inflammation. Fifty-four pulp tissue samples were collected from healthy donors with the diagnosis of reversible pulpitis, symptomatic irreversible pulpitis, and healthy pulp. Twelve pulp samples from each group were homogenized and total protein, ROS, GSH, and GST were measured by spectrophotometer. The remaining 6 samples from each group were prepared for paraffin block and used for the histopathologic and immunohistochemical evaluation of oxidative stress parameters and TUNEL labeling. Data were analyzed statistically. The results revealed that total protein levels significantly decreased; however, ROS levels increased in both reversible and irreversible pulpitis compared to the healthy pulp (p < 0.01). Also, as inflammation increases, GST enzyme levels decrease while GSH levels increase significantly (p < 0.05). It was found that the number of TUNEL (+) cells was increased in irreversible pulpitis samples compared to healthy and reversible pulpitis groups (p < 0.05). GSTP1 and GSH immunoreactivity were also observed in irreversible pulpitis samples. It has been revealed that caries-related inflammation alters the oxidative stress cycle in dental pulp tissue. The increase in GSH levels in the inflamed dental pulp due to the increase in ROS levels may improve the defensive ability of the dental pulp. There is a relationship between oxidative stress and inflammation. Control of excessive oxidative stress in pulpitis can stimulate reparative and regenerative processes. The present findings may provide an overview of the management of oxidative stress in cases with pulpitis during regenerative treatments.

Diabetes mellitus, defined as a fasting plasma glucose of ≥126 mg/dL or a glycosylated hemoglobin A1c level (HbA1c) of ≥6.5%, afflicts ≈12.9% of adults in the United States and nearly 285 million adults worldwide.1,2 Diabetes mellitus is a major risk factor for the development of cardiovascular disease, independently conferring a 2-fold excess risk of coronary heart disease and stroke.3 Macrovascular events in diabetes mellitus remain the leading cause of mortality, and the burden of cardiovascular disease attributable to diabetes mellitus has increased over the past decade.4 An increase in the prevalence of obesity has contributed to the rise in diabetes mellitus. Additionally, obesity independently increases the risk of cardiovascular disease in patients with diabetes mellitus.5 Although strict glycemic control unequivocally reduces the microvascular complications of diabetes mellitus, the macrovascular benefits of intensive therapy have been difficult to establish, with conflicting results from large clinical trials.6–9 Multifactorial strategies are recommended to reduce cardiovascular risk in diabetes mellitus through enhanced glycemic control, blood pressure reduction, lipid management, weight loss, and physical activity.10 Unfortunately, despite aggressive interventions for hyperglycemia, <50% of patients achieve standard HbA1c targets with conventional therapy.11 Polypharmacy is required to achieve glycemic control in the majority of patients within 3 years of diagnosis.12 Although combinations of drug classes can synergistically target multiple pathophysiological defects, novel therapies are required to manage diabetes mellitus and mitigate cardiovascular risks. Dipeptidyl-peptidase IV (DPP-IV) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist incretin therapies were developed to complement conventional treatment options for diabetes mellitus. Despite promising initial reports of cardioprotective effects, DPP-IV inhibitors have failed to demonstrate improved cardiovascular outcomes in large clinical trials.13–15 Randomized studies to evaluate cardiovascular outcomes associated with GLP-1 receptor agonists are currently underway. This review presents …

For people with diabetes mellitus to achieve optimal glycaemic control, motivation to perform self-management is important. The research team wanted to determine whether or not psychological interventions are clinically effective and cost-effective in increasing self-management and improving glycaemic control. The first objective was to determine the clinical effectiveness of psychological interventions for people with type 1 diabetes mellitus and people with type 2 diabetes mellitus so that they have improved (1) glycated haemoglobin levels, (2) diabetes self-management and (3) quality of life, and fewer depressive symptoms. The second objective was to determine the cost-effectiveness of psychological interventions. The following databases were accessed (searches took place between 2003 and 2016): MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, PsycINFO, EMBASE, Cochrane Controlled Trials Register, Web of Science, and Dissertation Abstracts International. Diabetes conference abstracts, reference lists of included studies and Clinicaltrials.gov trial registry were also searched. Systematic review, aggregate meta-analysis, network meta-analysis, individual patient data meta-analysis and cost-effectiveness modelling were all used. Risk of bias of randomised and non-randomised controlled trials was assessed using the Cochrane Handbook (Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928). Systematic review, meta-analysis, cost-effectiveness analysis and patient and public consultation were all used. Settings in primary or secondary care were included. Adolescents and children with type 1 diabetes mellitus and adults with types 1 and 2 diabetes mellitus were included. The interventions used were psychological treatments, including and not restricted to cognitive-behavioural therapy, counselling, family therapy and psychotherapy. Glycated haemoglobin levels, self-management behaviours, body mass index, blood pressure levels, depressive symptoms and quality of life were all used as outcome measures. A total of 96 studies were included in the systematic review (n = 18,659 participants). In random-effects meta-analysis, data on glycated haemoglobin levels were available for seven studies conducted in adults with type 1 diabetes mellitus (n = 851 participants) that demonstrated a pooled mean difference of -0.13 (95% confidence interval -0.33 to 0.07), a non-significant decrease in favour of psychological treatment; 18 studies conducted in adolescents/children with type 1 diabetes mellitus (n = 2583 participants) that demonstrated a pooled mean difference of 0.00 (95% confidence interval -0.18 to 0.18), indicating no change; and 49 studies conducted in adults with type 2 diabetes mellitus (n = 12,009 participants) that demonstrated a pooled mean difference of -0.21 (95% confidence interval -0.31 to -0.10), equivalent to reduction in glycated haemoglobin levels of -0.33% or ≈3.5 mmol/mol. For type 2 diabetes mellitus, there was evidence that psychological interventions improved dietary behaviour and quality of life but not blood pressure, body mass index or depressive symptoms. The results of the network meta-analysis, which considers direct and indirect effects of multiple treatment comparisons, suggest that, for adults with type 1 diabetes mellitus (7 studies; 968 participants), attention control and cognitive-behavioural therapy are clinically effective and cognitive-behavioural therapy is cost-effective. For adults with type 2 diabetes mellitus (49 studies; 12,409 participants), cognitive-behavioural therapy and counselling are effective and cognitive-behavioural therapy is potentially cost-effective. The results of the individual patient data meta-analysis for adolescents/children with type 1 diabetes mellitus (9 studies; 1392 participants) suggest that there were main effects for age and diabetes duration. For adults with type 2 diabetes mellitus (19 studies; 3639 participants), baseline glycated haemoglobin levels moderated treatment outcome. Aggregate meta-analysis was limited to glycaemic control for type 1 diabetes mellitus. It was not possible to model cost-effectiveness for adolescents/children with type 1 diabetes mellitus and modelling for type 2 diabetes mellitus involved substantial uncertainty. The individual patient data meta-analysis included only 40-50% of studies. This review suggests that psychological treatments offer minimal clinical benefit in improving glycated haemoglobin levels for adults with type 2 diabetes mellitus. However, there was no evidence of benefit compared with control interventions in improving glycated haemoglobin levels for people with type 1 diabetes mellitus. Future work should consider the competency of the interventionists delivering a therapy and psychological approaches that are matched to a person and their life course. This study is registered as PROSPERO CRD42016033619. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 28. See the NIHR Journals Library website for further project information.

Isolation and Characterization of Human Dental Pulp Stem Cells from Cryopreserved Pulp Tissues Obtained from Teeth with Irreversible Pulpitis

Comparative analysis of S100 protein expression in healthy and irreversibly inflamed human dental pulps: A systematic review

The clinical use of mesenchymalstem cells (MSCs) in regenerative medicine either intissue repair or tissue reconstruction has given highly interesting results thanks to their particular nature. Sources that have attracted the attention of medical scientists from where stem cells (SCs) in adults could be obtained are different and, dental tissues have certainly become an optimal source of MSCs. Dental tissue is a main reservoir of two types of MSCs dentalbud (DBSCs) that constitute the immatureprecursorof the tooth and dental pulp (DPSCs) that are derived from dental inner pulp and partly from dental follicle tissue and can differentiate into several cell phenotypes as osteoblast, chondrocyte, hepatocytes, cardiomyocytes, neuron and β cells. Normal impacted third molars and tooth buds were collected from adults and adolescents underwent to extractions for orthodontic reasons. The expression of the five stemness genes Nanog, OCT4, Sox2, c-Myc and Klf4 were investigated by qRT-PCR in two different dental stem/progenitor cells: dental pulp stem cells (DPSCs) and stem cells from dental bud (DBSCs), differentiated toward osteoblastic phenotype and not. Both DPSCs and DBSCs are easy to access and we found their expression of the typical mesenchymal stemness makers and osteogenic capacity due to the effective presence of embryonic gene regulators like Nanog, OCT4, Sox2, c-Myc and Klf4. Both DBSCs and DPSCs could represent a valid tool inregenerative medicine and translational applications. The results depicted here provide, for the first time to our knowledge, a comparative outcome about the stemness properties generated from accessible tissues such as DPSCs and DBSCs. These two types of SCs showed few different distinctive genetic traits supposedly in relation to their origin, location and stage of maturation. Certainly these SCs reserve solid potential for human clinical application in autologous procedure for bone, hard tissue and soft tissue regeneration, easy to isolate, ready availability, high-biocompatibility and safety and no ethical restrictions.

Diabetes is an increasingly prevalent chronic disease throughout the world. It is imperative for patients to have access to reliable treatment and resources in order to avoid long-term complications. Economic and social factors contribute to the accessibility of these resources and have a direct impact on diabetes management. Socioeconomic status (SES) presents challenges to diabetic management due to financial and geographical access to care, medications, educational resources, healthy food options, and physical activity. The coronavirus (COVID-19) pandemic exacerbated these challenges, especially during the height of lockdowns. Therefore, it is important to gain insight into how the pandemic challenged diabetes management, taking into consideration socioeconomic disparities. The objective is to assess how the COVID-19 pandemic has impacted the care of chronic diabetic patients internationally and determine how these outcomes vary between patients of different socioeconomic classes. The following study was designed as a scoping review and utilized PubMed, EMBASE, CINAHL, and Web of Science. A Boolean search strategy combined search terms as follows: (((COVID-19) AND (diabetes)) AND ((socioeconomic factors) OR (social inequality OR standard of living))) AND (treatment OR management). Inclusion criteria included studies addressing diabetic patients, socioeconomic variables (income, occupation, level of education, and ethnicity), glycemic control, and degree of access to quality healthcare. Studies exploring the pathophysiology of COVID-19 or diabetes mellitus were excluded. In addition, studies were chosen between the years 2020 and 2022. The search resulted in 214 articles. The full-text assessment was then conducted on the remaining 67 articles. After screening for eligibility and relevance, 19 articles were retained for this review. The results of this study indicate that 8 out of the 18 studies revealed worse outcomes for those with diabetes mellitus and concomitant COVID-19 infection. Patients with diabetes were more likely to be hospitalized and represent a larger percentage of COVID-19 fatalities. In addition, patients with diabetes and co-morbid COVID-19 infection were more likely to have a higher hemoglobin A1c (HbA1c), belong to a lower SES, and have worse glycemic control due to pandemic-associated lockdown. In order to combat the effects of the pandemic, many countries created novel and innovative management strategies. Overall, there are positive and negative effects from the pandemic on diabetic management strategies. This scoping review identified successes in diabetic treatment under pandemic conditions and areas that need optimization. The successful adaptations of many nations convey the capacity for new policy implementation to care for diabetic patients regardless of SES.

Differentially Expressed Genes in Dental Pulp Tissues of Individuals With Symptomatic Irreversible Pulpitis With and Without History of COVID-19

Direct visualization of the spatial relationships of the dental pulp tissue at the whole-organ has remained challenging. CLARITY (Clear Lipid-exchanged Acrylamide Tissue hYdrogel) is a tissue clearing method that has enabled successful 3-dimensional (3D) imaging of intact tissues with high-resolution and preserved anatomic structures. We used CLARITY to study the whole human dental pulp with emphasis on the neurovascular components. Dental pulps from sound teeth were CLARITY-cleared, immunostained for PGP9.5 and CD31, as markers for peripheral neurons and blood vessels, respectively, and imaged with light sheet microscopy. Visualization of the whole dental pulp innervation and vasculature was achieved. Innervation comprised 40% of the dental pulp volume and the vasculature another 40%. Marked innervation morphological differences between uni- and multiradicular teeth were found, also distinct neurovascular interplays. Quantification of the neural and vascular structures distribution, diameter and area showed that blood vessels in the capillary size range was twice as high as that of nerve fibers. In conclusion whole CLARITY-cleared dental pulp samples revealed 3D-morphological neurovascular interactions that could not be visualized with standard microscopy. This represents an outstanding tool to study the molecular and structural intricacies of whole dental tissues in the context of disease and treatment methods.

Objective. To analyze the evolution of the concept of health literacy (HL) in people with diabetes mellitus (DM) according to the Rodgers approach. Methods. The Rodgers approach was used, based on a scoping review that followed the steps of the JBI. Only methodologically clear studies that Only studies (articles) that clearly addressed HA in DM were included. Primary sources from health databases (e.g. PubMed, Scopus, Web of Science, SciELO, LILACS and BDENF) and grey literature (e.g. theses, dissertations and guides) were analysed via university repositories, Google Scholar, the Brazilian Digital Library of Theses and Dissertations and the CAPES Journal Portal (a Brazilian research support agency). The protocol was registered on the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/Y2T3R). Results. A total of 197 studies were selected, identifying seven key attributes of health literacy (HA): understanding, application, seeking, communication, critical appraisal, and sociocultural competencies related to diabetes. A total of 197 studies were selected to identify seven key attributes of health literacy (HA), such as understanding, application, seeking, communication, critical appraisal, and sociocultural competencies related to diabetes. Background factors (e.g., educational level and age) and outcomes (e.g., self-care, adherence, and glycemic control) were also examined. Conclusion. HA has evolved from basic literacy to digital and multidimensional competence, which presents challenges in vulnerable populations. HA is essential for the autonomy and effective management of diabetes mellitus (DM), highlighting the need for personalized educational interventions, primarily in primary care.

The aortic wall thickness of diabetes mellitus rat models after routine physical exercise