Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo.

Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro. For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques. However, the biosafety and efficacy; long-term stability of nanoparticles, and the capacity for drug release must be improved for clinical implementation. In fact, MSCs are vehicles for drug delivery with nanoparticles and also show low toxicity but inefficient accumulation in tumor sites by clearance of reticuloendothelial organs. To solve these problems, the internalization or conjugation of drug-loaded nanoparticles should be improved in MSCs. Finally, CXCR4 may prove to be a promising target for immunotherapy and cancer treatment since the delivery of siRNA to knock down this alpha chemokine receptor or CXCR4 antagonism has been shown to disrupt tumor-stromal interactions.

Adult Mesenchymal Stem Cells from Oral Cavity and Surrounding Areas: Types and Biomedical Applications.

Adult mesenchymal stem cells are those obtained from the conformation of dental structures (DMSC), such as deciduous and permanent teeth and other surrounding tissues. Background: The self-renewal and differentiation capacities of these adult stem cells allow for great clinical potential. Because DMSC are cells of ectomesenchymal origin, they reveal a high capacity for complete regeneration of dental pulp, periodontal tissue, and other biomedical applications; their differentiation into other types of cells promotes repair in muscle tissue, cardiac, pancreatic, nervous, bone, cartilage, skin, and corneal tissues, among others, with a high predictability of success. Therefore, stem and progenitor cells, with their exosomes of dental origin and surrounding areas in the oral cavity due to their plasticity, are considered a fundamental pillar in medicine and regenerative dentistry. Tissue engineering (MSCs, scaffolds, and bioactive molecules) sustains and induces its multipotent and immunomodulatory effects. It is of vital importance to guarantee the safety and efficacy of the procedures designed for patients, and for this purpose, more clinical trials are needed to increase the efficacy of several pathologies. Conclusion: From a bioethical and transcendental anthropological point of view, the human person as a unique being facilitates better clinical and personalized therapy, given the higher prevalence of dental and chronic systemic diseases.

The Bluegreen Algae (AFA) Consumption over 48 Hours Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood).

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA-Aphanizomenon flos aquae-algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 A.M.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects.

Elevated Systemic L-Kynurenine/L-Tryptophan Ratio and Increased IL-1 Beta and Chemokine (CX3CL1, MCP-1) Proinflammatory Mediators in Patients with Long-Term Titanium Dental Implants.

Titanium is the mean biocompatible metal found in dental titanium alloys (Ti-6Al-4V). The safety of certain dental biomaterial amalgams has been questioned in patients. The levels of several systemic cytokines (interleukin (IL)-1 beta, IL-4: pg/mL) and chemokines (monocyte chemoattractant protein-1 (MCP-1), soluble fractalkine (CX3CL1: pg/mL) were determined using ELISA and compared between these study groups. The study included 30 controls without dental materials (cont), 57 patients with long-term titanium dental implants plus amalgams (A + I group) as well as 55 patients with long-term dental amalgam alone (A group). All patients (except controls) have had dental titanium implants (Ti-6Al-4V) and/or amalgams for at least 10 years (average: 15 years). We evaluated whether systemic levels of cytokines/chemokines, kyn/L-trp ratio and aromatic amino acid levels (HPLC: mM/L, Phe, L-Trp, His, Treo) could be altered in patients with long-term dental titanium and/or amalgams. These systemic markers were evaluated in 142 patients. The A + I group had higher L-Kynurenine/L-Tryptophan ratios than patients with long-term dental amalgam fillings alone (A). In addition, levels of IL-1 Beta cytokine, CX3CL1 and MCP-1 chemokines were higher in the A + I group than in the A group (A). The increased L-kyn/L-trp ratio and MCP-1 and fractalkine receptor (CX3CR1) elevations could suggest enhanced chemotactic responses by these chemokines in the A + I group.

The Long-Term Algae Extract (Chlorella and Fucus sp) and Aminosulphurate Supplementation Modulate SOD-1 Activity and Decrease Heavy Metals (Hg++, Sn) Levels in Patients with Long-Term Dental Titanium Implants and Amalgam Fillings Restorations.

The toxicity of heavy metals such as Hg++ is a serious risk for human health. We evaluated whether 90 days of nutritional supplementation (d90, n = 16) with Chlorella vulgaris (CV) and Fucus sp extracts in conjunction with aminosulphurate (nutraceuticals) supplementation could detox heavy metal levels in patients with long-term titanium dental implants (average: three, average: 12 years in mouth) and/or amalgam fillings (average: four, average: 15 years) compared to baseline levels (d0: before any supplementation, n = 16) and untreated controls (without dental materials) of similar age (control, n = 21). In this study, we compared levels of several heavy metals/oligoelements in these patients after 90 days (n = 16) of nutritional supplementation with CV and aminozuphrates extract with their own baseline levels (d0, n = 16) and untreated controls (n = 21); 16 patients averaging 44 age years old with long-term dental amalgams and titanium implants for at least 10 years (average: 12 years) were recruited, as well as 21 non-supplemented controls (without dental materials) of similar age. The following heavy metals were quantified in hair samples as index of chronic heavy metal exposure before and after 90 days supplementation using inductively coupled plasma-mass spectrometry (ICP-MS) and expressed as µg/g of hair (Al, Hg++, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, and Ti). We also measured several oligoelements (Ca++, Mg++, Na+, K+, Cu++, Zn++, Mn++, Cr, V, Mo, B, I, P, Se, Sr, P, Co, Fe++, Ge, Rb, and Zr). The algae and nutraceutical supplementation during 90 consecutive days decreased Hg++, Ag, Sn, and Pb at 90 days as compared to baseline levels. The mercury levels at 90 days decreased as compared with the untreated controls. The supplementation contributed to reducing heavy metal levels. There were increased lithium (Li) and germanium (Ge) levels after supplementation in patients with long-term dental titanium implants and amalgams. They also (d90) increased manganesum (Mn++), phosphorum (P), and iron (Fe++) levels as compared with their own basal levels (d0) and the untreated controls. Finally, decreased SuperOxide Dismutase-1 (SOD-1) activity (saliva) was observed after 90 days of supplementation as compared with basal levels (before any supplementation, d0), suggesting antioxidant effects. Conversely, we detected increased SOD-1 activity after 90 days as compared with untreated controls. This SOD-1 regulation could induce antioxidant effects in these patients. The long-term treatment with algae extract and aminosulphurates for 90 consecutive days decreased certain heavy metal levels (Hg++, Ag, Sn, Pb, and U) as compared with basal levels. However, Hg++ and Sn reductions were observed after 90 days as compared with untreated controls (without dental materials). The dental amalgam restoration using activated nasal filters in conjunction with long-term nutritional supplementation enhanced heavy metals removal. Finally, the long-term supplementation with these algae and aminoazuphrates was safe and non-toxic in patients. These supplements prevented certain deficits in oligoelements without affecting their Na+/K+ ratios after long-term nutraceutical supplementation.

Origanum majorana Essential Oil Inhalation during Neurofeedback Training Reduces Saliva Myeloperoxidase Activity at Session-1 in Bruxistic Patients.

Introduction: Bruxism affects teeth and provokes sleep alterations. We evaluated whether saliva Myeloperoxidase (MPO) activity could be reduced after 21 neurofeedback training (NO) sessions in Origanum majorana (AE) bruxistic-treated patients (n = 12 patients, 120 saliva samples). The term divergence evaluates cerebral activity, which was compared between bruxistic patients with/without this essential oil exposure during 21 NO training sessions (n = 12, n = 120 saliva samples). The nasal filter used allow us to vehiculizate this Origanum majorana essential oil in patients. MPO activity was measured in six training NO sessions (Session S1, 6, 12, 18, 21). We included a total of 104 patients and 500 saliva samples. Results: there was a fast reduction in MPO activity after NO session-1 in bruxistic patients; divergence (an index of NO training brain efficacy) is the difference in cerebral activity found between pre-training and post-training levels. Thus, Divergence can fluctuate during NO training before reaching a final calm state after many sessions (21). Repeated NO training lead to habituation in so far as cerebral activity as well as MPO activity after 21 training sessions. Origanum majorana essential oil modulates cerebral activity at certain training sessions in bruxistic patients. Stress levels were reduced on the perceived stress scores (PSS: Cohen Scale) after 21 NO sessions than for those bruxistic without NO training sessions. Conclusions: MPO activity could predict stress level in bruxistic patients and repeated NO reduced their stress level; Origanum majorana essential oil enhanced these anxiolytic effects.

Increased Systemic Malondialdehyde Levels and Decreased Mo/Co, Co/Fe2+ Ratios in Patients with Long-Term Dental Titanium Implants and Amalgams.

INTRODUCTION: the biological safety of dental biomaterials has been questioned in human studies. MATERIAL AND METHODS: Several heavy metals/oligoelements were compared by Inductive Coupled Mass Spectrometry (ICP-MS) in hair samples from 130 patients (n = 54 patients with long-term titanium dental implants and amalgams (A + I group), 51 patients with long-term dental amalgam alone (A group), as well as controls (n = 25: without dental materials) of similar age. All patients (except controls) had had titanium dental implants and/or dental amalgams for at least 10 years (average: 17). We evaluated whether A + I patients could present higher systemic malondialdehyde levels (MDA) as compared to the A group. RESULTS: The A + I group have lower molybdenum levels (A + I) and reduced Mo/Co and Mo/Fe2+ ratios, which could predispose them to oxidative stress by raising MDA levels as compared to the A group alone; our findings suggest that higher Co levels could enhance oxidative stress in the A + I group. However, there were no differences on metals from titanium alloy (Ti-6Al), Cr from crowns or Hg2+, Sn, Zn2+, Cu2+ levels between the A + I and A groups. CONCLUSION: patients with long-term dental titanium and amalgams have systemic oxidative stress due to rising MDA levels and lower Mo/Co and Mo/Fe2+ ratios than those with amalgams alone.

Zirconia implants and peek restorations for the replacement of upper molars.

BACKGROUND: One of the disadvantages of the zirconia implants is the lack of elasticity, which is increased with the use of ceramic or zirconia crowns. The consequences that could result from this lack of elasticity have led to the search for new materials with improved mechanical properties. CASE PRESENTATION: A patient who is a 45-year-old woman, non-smoker and has no medical record of interest with a longitudinal fracture in the palatal root of molar tooth 1.7 and absence of tooth 1.6 was selected in order to receive a zirconia implant with a PEEK-based restoration and a composite coating. The following case report describes and analyses treatment with zirconia implants in molars following a flapless surgical technique. Zirconia implants are an alternative to titanium implants in patients with allergies or who are sensitive to metal alloys. However, one of the disadvantages that they have is their lack of elasticity, which increases with the use of ceramic or zirconia crowns. The consequences that can arise from this lack of elasticity have led to the search for new materials with better mechanical properties to cushion occlusal loads. PEEK-based restoration in implant prosthetics can compensate these occlusal forces, facilitating cushioning while chewing. CONCLUSION: This procedure provides excellent elasticity and resembles natural tooth structure. This clinical case suggests that PEEK restorations can be used in zirconia implants in dentistry.

Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma.

BACKGROUND: The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems. OBJECTIVES: To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings. MATERIALS AND METHODS: 55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (µg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42). FINDINGS: Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury. CONCLUSIONS: Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity.

A pilot study of postoperative pain felt after two implant surgery techniques: a randomized blinded prospective clinical study.

PURPOSE: To evaluate postoperative pain after successful implant surgery and compare pain experienced using conventional flap and flapless techniques. MATERIALS AND METHODS: Between January 2007 and September 2012, consecutive patients with bilateral partially edentulous maxillae or mandibles were included in the study. Patients were randomly allocated to receive implants with an atraumatic flapless procedure or with a conventional flap procedure in a split-mouth design in a two-stage surgery. This randomized blinded prospective clinical study considered each patient as one unit. The data were analyzed using the Mann-Whitney and chi-square tests. RESULTS: One hundred eight implants were placed in 19 patients. Radiographic and clinical examination showed that all implants were successful. Postoperative pain was significantly more intense after surgery with the conventional flap technique than after surgery with the atraumatic flapless technique. Likewise, the inflammatory response was more intense with the flap technique. CONCLUSIONS: Postoperative pain depends on the surgical technique used and is less intense with a flapless technique.