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Pyrogens are fever-inducing substances routinely investigated in health products through tests such as the Rabbit Pyrogen Test (RPT), the Limulus Amebocyte Lysate (LAL), and the Monocyte Activation Test (MAT). However, the applications of the MAT for medical devices and biomaterials remain limited. This work aimed to overview the studies evaluating the pyrogenicity of medical devices and biomaterials using the MAT, highlighting its successes and potential challenges. An electronic search was performed by December 2023 in PubMed, Scopus, and Web of Science, identifying 321 records which resulted in ten selected studies. Data were extracted detailing the tested materials, MAT variants, interferences, and comparisons between methods. Methodological quality was assessed using the ToxRTool, and the results were synthesized descriptively. The selected studies investigated various materials, including polymers, metals, and natural compounds, employing the different biological matrices of the MAT. Results showed the MAT's versatility, with successful detection of pyrogens in most materials tested, though variability in sensitivity was noted based on the material and testing conditions. Challenges remain in optimizing protocols for different material properties, such as determining the best methods for direct contact versus eluate testing and addressing the incubation conditions. In conclusion, the MAT demonstrates significant potential as a pyrogen detection method for medical devices and biomaterials. However, continued research is essential to address existing gaps, optimize protocols, and validate the test across a broader range of materials.
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Materiales Biocompatibles , Equipos y Suministros , Monocitos , Pirógenos , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Pirógenos/análisis , Materiales Biocompatibles/química , Humanos , AnimalesRESUMEN
OBJECTIVES: This in vitro study is aimed at assessing whether implant primary stability is influenced by implant length in artificial bone with varying densities. MATERIALS AND METHODS: A total of 120 truncated-conical implants (60 long-length: 3p L, 3.8 × 14 mm; 60 short-length: 3p S, 3.8 × 8 mm) were inserted into 20, 30, and 40 pounds per cubic foot (PCF) density polyurethane blocks. The insertion torque (IT), removal torque (RT), and resonance frequency analysis (RFA) values were recorded for each experimental condition. RESULTS: In 30 and 40 PCF blocks, 3p S implants exhibited significantly higher IT values (90 and 80 Ncm, respectively) than 3p L (85 and 50 Ncm, respectively). Similarly, RT was significantly higher for 3p S implants in 30 and 40 PCF blocks (57 and 90 Ncm, respectively). However, there were no significant differences in RFA values, except for the 20 PCF block, where 3pS implants showed significantly lower values (63 ISQ) than 3p L implants (67 ISQ) in both the distal and mesial directions. CONCLUSIONS: These results demonstrated that the implant's length mainly influences the IT and RT values in the polyurethane blocks that mimic the mandibular region of the bone, resulting in higher values for the 3p S implants, while the RFA values remained unaffected. However, in the lowest density block simulating the maxillary bone, 3p L implants exhibited significantly higher ISQ values. CLINICAL RELEVANCE: Therefore, our data offer valuable insights into the biomechanical behavior of these implants, which could be clinically beneficial for enhancing surgical planning.
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Implantes Dentales , Maxilar , Poliuretanos , Análisis de Frecuencia de Resonancia , TorqueRESUMEN
Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to investigate a series of RSV derivatives (1a-j) with better pharmacokinetic profiles. At first, their cytocompatibility at different concentrations was tested on gingival fibroblasts (HGFs). Among them, derivatives 1d and 1h significantly increased cell viability compared to the reference compound RSV. Thus, 1d and 1h were investigated for cytotoxicity, proliferation, and gene expression in HGFs, endothelial cells (HUVECs), and oral osteoblasts (HOBs), which are the main cells involved in oral wound healing. For HUVECs and HGFs, the morphology was also evaluated, while for HOBs ALP and mineralization were observed. The results showed that both 1d and 1h did not exert negative effects on cell viability, and at a lower concentration (5 µM) both even significantly enhanced the proliferative rate, compared to RSV. The morphology observations pointed out that the density of HUVECs and HGFs was promoted by 1d and 1h (5 µM) and mineralization was promoted in HOBs. Moreover, 1d and 1h (5 µM) induced a higher eNOS mRNA level in HUVECs, higher COL1 mRNA in HGFs, and higher OCN in HOBs, compared to RSV. The appreciable physicochemical properties and good enzymatic and chemical stability of 1d and 1h, along with their promising biological properties, provide the scientific basis for further studies leading to the development of RSV-based agents useful in oral tissue repair.
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Células Endoteliales , Fibroblastos , Resveratrol/farmacología , Células Cultivadas , Fibroblastos/metabolismo , Cicatrización de Heridas , ARN Mensajero/metabolismoRESUMEN
Essential oils (EOs) are mixtures of volatile compounds belonging to several chemical classes derived from aromatic plants using different distillation techniques. Recent studies suggest that the consumption of Mediterranean plants, such as anise and laurel, contributes to improving the lipid and glycemic profile of patients with diabetes mellitus (DM). Hence, the aim of the present study was to investigate the potential anti-inflammatory effect of anise and laurel EOs (AEO and LEO) on endothelial cells isolated from the umbilical cord vein of females with gestational diabetes mellitus (GDM-HUVEC), which is a suitable in vitro model to reproduce the pro-inflammatory phenotype of a diabetic endothelium. For this purpose, the Gas Chromatographic/Mass Spectrometric (GC-MS) chemical profiles of AEO and LEO were first analyzed. Thus, GDM-HUVEC and related controls (C-HUVEC) were pre-treated for 24 h with AEO and LEO at 0.025% v/v, a concentration chosen among others (cell viability by MTT assay), and then stimulated with TNF-α (1 ng/mL). From the GC-MS analysis, trans-anethole (88.5%) and 1,8-cineole (53.9%) resulted as the major components of AEO and LEO, respectively. The results in C- and GDM-HUVEC showed that the treatment with both EOs significantly reduced: (i) the adhesion of the U937 monocyte to HUVEC; (ii) vascular adhesion molecule-1 (VCAM-1) protein and gene expression; (iii) Nuclear Factor-kappa B (NF-κB) p65 nuclear translocation. Taken together, these data suggest the anti-inflammatory efficacy of AEO and LEO in our in vitro model and lay the groundwork for further preclinical and clinical studies to study their potential use as supplements to mitigate vascular endothelial dysfunction associated with DM.
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Diabetes Gestacional , Aceites Volátiles , Humanos , Embarazo , Femenino , Monocitos/metabolismo , Células Endoteliales/metabolismo , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/metabolismo , Aceites Volátiles/farmacología , Aceites Volátiles/metabolismo , Células U937 , Adhesión Celular , FN-kappa B/metabolismo , Cordón Umbilical/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismoRESUMEN
Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an "endothelial hyperglycemic memory" model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo.
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Antioxidantes/metabolismo , Senescencia Celular , Diabetes Gestacional/fisiopatología , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/patología , Modelos Biológicos , Estrés Oxidativo , Células Cultivadas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteína p300 Asociada a E1A/genética , Proteína p300 Asociada a E1A/metabolismo , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Técnicas In Vitro , Embarazo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
This study aimed to evaluate the effects of a new photodynamic protocol (ALAD-PDT) on primary human osteoblasts (hOBs). The ALAD-PDT protocol consists of a heat-sensitive gel with 5% 5-delta aminolevulinic acid commercialized as Aladent (ALAD), combined with 630 nm LED. For this purpose, the hOBs, explanted from human mandible bone fragments, were used and treated with different ALAD concentrations (10%, 50%, 100% v/v) incubated for 45 min and immediately afterwards irradiated with a 630 nm LED device for 7 min. The untreated and unirradiated cells were considered control (CTRL). The cellular accumulation of the photosensitizer protoporphyrin IX (PpIX), the proliferation, the alkaline phosphatase (ALP) activity, and the calcium deposition were assessed. All concentrations (10, 50, 100%) determined a significant increment of PpIX immediately after 45 min of incubation (0 h) with the highest peak by ALAD (100%). The consequent 7 min of light irradiation caused a slight decrease in PpIX. At 48 h and 72 h, any increment of PpIX was observed. The concentration 100% associated with LED significantly increased hOB proliferation at 48 h (+ 46.83%) and 72 h (+ 127.75%). The 50% and 100% concentrations in combination to the red light also stimulated the ALP activity, + 12.910% and + 14.014% respectively. The concentration 100% with and without LED was selected for the assessment of calcium deposition. After LED irradiation, a significant increase in calcium deposition was observed and quantified (+ 72.33%). In conclusion, the ALAD-PDT enhanced proliferation, the ALP activity, and mineralized deposition of human oral osteoblasts, highlighting a promising potential for bone tissue regeneration.
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Ácido Aminolevulínico , Fotoquimioterapia , Humanos , Ácido Aminolevulínico/farmacología , Fotoquimioterapia/métodos , Calcio , Protoporfirinas , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , OsteoblastosRESUMEN
Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose of this study was to evaluate the response of human gingival fibroblasts (hGDFs) to titanium implant discs (Implacil De Bortoli, Brazil) having different micro and nano-topography: machined (Ti-M) versus sandblasted/double-etched (Ti-S). The secondary aim was to investigate the effect of the macrogeometry of the discs on cells: linear-like (Ti-L) versus wave-like (Ti-W) surfaces. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis showed that the Ti-S surfaces were characterized by a significantly higher micro and nano roughness and showed the 3D macrotopography of Ti-L and Ti-W surfaces. For in vitro analyses, the hGDFs were seeded into titanium discs and analyzed at 1, 3, and 5 days for adhesion and morphology (SEM) viability and proliferation (Cck-8 and MTT assays). The results showed that all tested surfaces were not cytotoxic for the hGDFs, rather the nano-micro and macro topography favored their proliferation in a time-dependent manner. Especially, at 3 and 5 days, the number of cells on Ti-L was higher than on other surfaces, including Ti-W surfaces. In conclusion, although further studies are needed, our in vitro data proved that the use of implant discs with Ti-S surfaces promotes the adhesion and proliferation of gingival fibroblasts, suggesting their use for in vivo applications.
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Adhesión Celular/efectos de los fármacos , Implantes Dentales , Encía/efectos de los fármacos , Oseointegración/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Encía/crecimiento & desarrollo , Humanos , Ensayo de Materiales , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Propiedades de Superficie/efectos de los fármacos , Titanio/química , Titanio/uso terapéuticoRESUMEN
Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD; hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation.
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Eritrocitos/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico/sangre , Diálisis Peritoneal , Diálisis Renal , Uremia/sangre , Anciano , GMP Cíclico/sangre , GMP Cíclico/metabolismo , Femenino , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Modelos Biológicos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Óxido Nítrico Sintasa/metabolismo , Nitritos/sangre , Nitrosación , FosforilaciónRESUMEN
Vascular calcification (VC) is an active and cell-mediated process that shares many common features with osteogenesis. Knowledge demonstrates that in the presence of risk factors, such as hypertension, vascular smooth muscle cells (vSMCs) lose their contractile phenotype and transdifferentiate into osteoblastic-like cells, contributing to VC development. Recently, menaquinones (MKs), also known as Vitamin K2 family, has been revealed to play an important role in cardiovascular health by decreasing VC. However, the MKs' effects and mechanisms potentially involved in vSMCs osteoblastic transdifferentiation are still unknown. The aim of this study was to investigate the possible role of menaquinone-4 (MK-4), an isoform of MKs family, in the modulation of the vSMCs phenotype. To achieve this, vascular cells from spontaneously hypertensive rats (SHR) were used as an in vitro model of cell vascular dysfunction. vSMCs from Wistar Kyoto normotensive rats were used as control condition. The results showed that MK-4 preserves the contractile phenotype both in control and SHR-vSMCs through a γ-glutamyl carboxylase-dependent pathway, highlighting its capability to inhibit one of the mechanisms underlying VC process. Therefore, MK-4 may have an important role in the prevention of vascular dysfunction and atherosclerosis, encouraging further in-depth studies to confirm its use as a natural food supplement.
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Aterosclerosis/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Osteogénesis/efectos de los fármacos , Vitamina K 2/análogos & derivados , Animales , Aterosclerosis/genética , Aterosclerosis/patología , Presión Sanguínea/genética , Ligasas de Carbono-Carbono/genética , Proliferación Celular , Transdiferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Hipertensión/genética , Hipertensión/patología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Ratas , Ratas Endogámicas SHR , Transducción de Señal/efectos de los fármacos , Vitamina K 2/farmacologíaRESUMEN
BACKGROUND: To evaluate whether exposure to GLP-1 receptor agonist Liraglutide could modulate pro-atherogenic alterations previously observed in endothelial cells obtained by women affected by gestational diabetes (GD), thus exposed in vivo to hyperglycemia, oxidative stress, and inflammation and to evaluate endothelial microvesicle (EMV) release, a new reliable biomarker of vascular stress/damage. METHODS: We studied Liraglutide effects and its plausible molecular mechanisms on monocyte cell adhesion and adhesion molecule expression and membrane exposure in control (C-) human umbilical vein endothelial cells (HUVEC) as well as in HUVEC of women affected by GD exposed in vitro to TNF-α. In the same model, we also investigated Liraglutide effects on EMV release. RESULTS: In response to TNF-α, endothelial monocyte adhesion and VCAM-1 and ICAM-1 expression and exposure on plasma membrane was greater in GD-HUVEC than C-HUVEC. This was the case also for EMV release. In GD-HUVEC, Liraglutide exposure significantly reduced TNF-α induced endothelial monocyte adhesion as well as VCAM-1 and ICAM-1 expression and exposure on plasma membrane. In the same cells, Liraglutide exposure also reduced MAPK/NF-kB activation, peroxynitrite levels, and EMV release. CONCLUSIONS: TNF-α induced pro-atherogenic alterations are amplified in endothelial cells chronically exposed to hyperglycemia in vivo. Liraglutide mitigates TNF-α effects and reduces cell stress/damage indicators, such as endothelial microvesicle (EMV) release. These results foster the notion that Liraglutide could exert a protective effect against hyperglycemia and inflammation triggered endothelial dysfunction.
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Aterosclerosis/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Factor de Necrosis Tumoral alfa/farmacología , Aterosclerosis/metabolismo , Femenino , Humanos , Hipoglucemiantes/farmacología , Molécula 1 de Adhesión Intercelular/metabolismo , Liraglutida/farmacología , Estrés Oxidativo/efectos de los fármacos , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.
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GMP Cíclico/metabolismo , Eritrocitos/metabolismo , Fallo Renal Crónico/metabolismo , Óxido Nítrico/biosíntesis , Anciano , Calmodulina/metabolismo , Eritrocitos/patología , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Fallo Renal Crónico/patología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Óxido Nítrico Sintasa de Tipo III/metabolismoRESUMEN
This study aimed to evaluate various biomechanical parameters associated with the primary stability of Maestro and Due Cone implants placed in low-density artificial bones, prepared using high-speed drilling with irrigation and low-speed drilling without irrigation. The insertion torque (IT), removal torque (RT), and implant stability quotient (ISQ) values were recorded for Maestro and Due Cone implants placed in low-density polyurethane blocks (10 and 20 pounds per cubic foot (PCF) with and without a cortical layer) prepared using high-speed and low-speed with or without irrigation using a saline solution, respectively. A three-way ANOVA model and Tukey's post-hoc test were conducted, presenting data as means and standard deviations. P-values equal to or less than 0.05 were considered statistically significant. No statistically significant differences in IT, RT, and ISQ between drilling speeds were observed. However, Maestro implants exhibited lower IT and RT values after high- and low-speed drilling across almost all polyurethane blocks, significantly evident in the 20 PCF density block for IT and in the 20 PCF density block with the cortical layer for the RT with low-speed drilling (IT: 47.33 ± 10.02 Ncm and 16.00 ± 12.49 Ncm for Due Cone and Maestro implants, respectively, with p < 0.01; RT: 44.67 ± 22.81 Ncm and 20.01 ± 4.36 Ncm for Due Cone and Maestro implants, respectively, with p < 0.05) and among the same implant types inserted in different bone densities. Additionally, the study found that for all bone densities and drilling speeds, both implants registered ISQ values exceeding 60, except for the lowest-density polyurethane block. Overall, it can be inferred that low-speed drilling without irrigation achieved biomechanical parameters similar to conventional drilling with both implant types, even with lower IT values in the case of Maestro implants. These findings suggest a promising potential use of low-speed drilling without irrigation in specific clinical scenarios, particularly when focusing on preparation depth or when ensuring proper irrigation is challenging.
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Zinc is known for its role in enhancing bone metabolism, cell proliferation, and tissue regeneration. Several studies proposed the incorporation of zinc into hydroxyapatite (HA) to produce biomaterials (ZnHA) that stimulate and accelerate bone healing. This systematic review aimed to understand the physicochemical characteristics of zinc-doped HA-based biomaterials and the evidence of their biological effects on osteoblastic cells. A comprehensive literature search was conducted from 2022 to 2024, covering all years of publications, in three databases (Web of Science, PUBMED, Scopus), retrieving 609 entries, with 36 articles included in the analysis according to the selection criteria. The selected studies provided data on the material's physicochemical properties, the methods of zinc incorporation, and the biological effects of ZnHA on bone cells. The production of ZnHA typically involves the wet chemical synthesis of HA and ZnHA precursors, followed by deposition on substrates using processes such as liquid precursor plasma spraying (LPPS). Characterization techniques confirmed the successful incorporation of zinc into the HA lattice. The findings indicated that zinc incorporation into HA at low concentrations is non-cytotoxic and beneficial for bone cells. ZnHA was found to stimulate cell proliferation, adhesion, and the production of osteogenic factors, thereby promoting in vitro mineralization. However, the optimal zinc concentration for the desired effects varied across studies, making it challenging to establish a standardized concentration. ZnHA materials are biocompatible and enhance osteoblast proliferation and differentiation. However, the mechanisms of zinc release and the ideal concentrations for optimal tissue regeneration require further investigation. Standardizing these parameters is essential for the effective clinical application of ZnHA.
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The purpose of this finite element analysis (FEA) was to evaluate the stress distribution within the prosthetic components and bone in relation to varying cement thicknesses (from 20 to 60 µm) utilized to attach a zirconia crown on a conometric cap. The study focused on two types of implants (Cyroth and TAC, AoN Implants, Grisignano di Zocco, Italy) featuring a Morse cone connection. Detailed three-dimensional (3D) models were developed to represent the bone structure (cortical and trabecular) and the prosthetic components, including the crown, cement, cap, abutment, and the implant. Both implants were placed 1.5 mm subcrestally and subjected to a 200 N load at a 45° inclination on the crown. The results indicated that an increase in cement thickness led to a reduction in von Mises stress on the cortical bone for both Cyroth and TAC implants, while the decrease in stress on the trabecular bone (apical zone) was relatively less pronounced. However, the TAC implant exhibited a higher stress field in the apical area compared to the Cyroth implant. In summary, this study investigated the influence of cement thickness on stress transmission across prosthetic components and peri-implant tissues through FEA analysis, emphasizing that the 60 µm cement layer demonstrated higher stress values approaching the material strength limit.
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Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although significant progress has been made in this field, innovative approaches are needed to reduce tumor incidence, progression, and spread. In particular, the development of cancer vaccines is currently ongoing as both a preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayer vesicles that carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce direct or indirect stimulation of the immune system. In particular, EX-based vaccines may cause an anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibiting disease development. This review delves into EX composition, biogenesis, and immune-modulating properties, exploring their role as a tool for prevention and therapy in solid tumors. Finally, we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.
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IMPORTANCE: Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals. OBJECTIVE: To identify genetic determinants of CHD that are specific to patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS: We studied 5 independent sets of CHD cases and CHD-negative controls from the Nurses' Health Study (enrolled in 1976 and followed up through 2008), Health Professionals Follow-up Study (enrolled in 1986 and followed up through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1517 CHD cases and 2671 CHD-negative controls, all with type 2 diabetes. Results in diabetic patients were compared with those in 737 nondiabetic CHD cases and 1637 nondiabetic CHD-negative controls from the Nurses' Health Study and Health Professionals Follow-up Study cohorts. Exposures included 2,543,016 common genetic variants occurring throughout the genome. MAIN OUTCOMES AND MEASURES: Coronary heart disease--defined as fatal or nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries. RESULTS: A variant on chromosome 1q25 (rs10911021) was consistently associated with CHD risk among diabetic participants, with risk allele frequencies of 0.733 in cases vs 0.679 in controls (odds ratio, 1.36 [95% CI, 1.22-1.51]; P = 2 × 10(-8)). No association between this variant and CHD was detected among nondiabetic participants, with risk allele frequencies of 0.697 in cases vs 0.696 in controls (odds ratio, 0.99 [95% CI, 0.87-1.13]; P = .89), consistent with a significant gene × diabetes interaction on CHD risk (P = 2 × 10(-4)). Compared with protective allele homozygotes, rs10911021 risk allele homozygotes were characterized by a 32% decrease in the expression of the neighboring glutamate-ammonia ligase (GLUL) gene in human endothelial cells (P = .0048). A decreased ratio between plasma levels of γ-glutamyl cycle intermediates pyroglutamic and glutamic acid was also shown in risk allele homozygotes (P = .029). CONCLUSION AND RELEVANCE: A single-nucleotide polymorphism (rs10911021) was identified that was significantly associated with CHD among persons with diabetes but not in those without diabetes and was functionally related to glutamic acid metabolism, suggesting a mechanistic link.
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Cromosomas Humanos Par 1 , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Diabetes Mellitus Tipo 2/epidemiología , Glutamato-Amoníaco Ligasa/genética , Ácido Glutámico/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genotipo , Ácido Glutámico/sangre , Glutamina/sangre , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Estados Unidos/epidemiologíaRESUMEN
Stabilization of dental implants in the sinus region with a bone height below 4 mm gen-erally requires a two-stage sinus floor elevation surgery. To improve this aspect, the aim of this retrospective study was to demonstrate the feasibility of performing a one-stage maxillary sinus augmentation using an innovative self-condensing implant design, even in case of a bone height close to 2 mm. Clinical and radiological outcomes from 54 patients (26 females; 28 males; 69 total implants positioned) were analyzed 3 years post-surgery. The three-dimensional grafts change was evaluated by Cone-Beam Computed Tomography (CBCT) before surgery (T0), immediately after surgery (T1), and 1-year post-surgery (T2). The sinus floor levels measured at the medial (M-W), middle (MD-W), and lateral (L-W) walls reported: M-W of 1.9 ± 2.4 mm (T1) and 1.7 ± 2.6 mm (T2); MD-W of -0.1 ± 2.7 mm (T1) and 0.7 ± 2.4 mm (T2); L-W of 3.1 ± 3.0 mm (T1) and 3.1 ± 3.0 mm (T2); besides a bone crest height (C-F) of 4.6 ± 2.0 mm (T1) and 12.1 ± 1.4 mm (T2). Moreover, after 3 years only 1 implant was lost, and so an implant survival rate of 98.55% was recorded. In conclusion, these results suggest the efficacy of using this implant design for a one-stage sinus lift approach, not only in terms of increased implant survival rate and decreased marginal bone loss, but also for its potential applicability in case of reduced bone height.
Asunto(s)
Elevación del Piso del Seno Maxilar , Masculino , Femenino , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Elevación del Piso del Seno Maxilar/métodos , Tomografía Computarizada de Haz Cónico , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía , Resultado del TratamientoRESUMEN
Combining tooth extraction and implant placement reduces the number of surgical procedures that a patient must undergo. Thus, the present study aimed to compare the stability of two types of conical implants (TAC and INTRALOCK) and another cylindrical one (CYROTH), inserted with a range of angulation of 15-20 degrees in low-density polyurethane blocks (10 and 20 pounds per cubic foot, PCF) with or without a cortical lamina (30 PCF), which potentially mimicked the post-extraction in vivo condition. For this purpose, a total of 120 polyurethane sites were prepared (10 for each implant and condition) and the Insertion Torque (IT), Removal Torque (RT), and Resonance Frequency Analysis (RFA) were measured, following a Three-Way analysis of variance followed by Tukey's post hoc test for the statistical analysis of data. The IT and RT values registered for all implant types were directly proportional to the polyurethane density. The highest IT was registered by INTRALOCK implants in the highest-density block (32.44 ± 3.28 Ncm). In contrast, the highest RFA, a well-known index of Implant Stability Quotient (ISQ), was shown by TAC implants in all clinical situations (up to 63 ISQ in the 20 PCF block without the cortical sheet), especially in lower-density blocks. Although more pre-clinical and clinical studies are required, these results show a better primary stability of TAC conical implants in all tested densities of this post-extraction model, with a higher ISQ, despite their IT.
RESUMEN
The issue of dental implant placement relative to the alveolar crest, whether in supracrestal, equicrestal, or subcrestal positions, remains highly controversial, leading to conflicting data in various studies. Three-dimensional (3D) Finite Element Analysis (FEA) can offer insights into the biomechanical aspects of dental implants and the surrounding bone. A 3D model of the jaw was generated using computed tomography (CT) scans, considering a cortical thickness of 1.5 mm. Subsequently, Morse cone implant-abutment connection implants were virtually positioned at the model's center, at equicrestal (0 mm) and subcrestal levels (-1 mm and -2 mm). The findings indicated the highest stress within the cortical bone around the equicrestally placed implant, the lowest stress in the -2 mm subcrestally placed implant, and intermediate stresses in the -1 mm subcrestally placed implant. In terms of clinical relevance, this study suggested that subcrestal placement of a Morse cone implant-abutment connection (ranging between -1 and -2 mm) could be recommended to reduce peri-implant bone resorption and achieve longer-term implant success.
RESUMEN
Extreme atrophy of the maxilla still poses challenges for clinicians. Some of the techniques used to address this issue can be complex, risky, expensive, and time consuming, often requiring skilled surgeons. While many commonly used techniques have achieved very high success rates, complications may arise in certain cases. In this context, the premaxillary device (PD) technique offers a simpler approach to reconstruct severely atrophic maxillae, aiming to avoid more complicated and risky surgical procedures. Finite element analysis (FEA) enables the evaluation of different aspects of dental implant biomechanics. Our results demonstrated that using a PD allows for an optimal distribution of stresses on the basal bone, avoiding tension peaks that can lead to bone resorption or implant failure. ANSYS® was used to perform localized finite element analysis (FEA), enabling a more precise examination of the peri-crestal area and the PD through an accurate mesh element reconstruction, which facilitated the mathematical solution of FEA. The most favorable biomechanical behavior was observed for materials such as titanium alloys, which helped to reduce stress levels on bone, implants, screws, and abutments. Additionally, stress values remained within the limits of basal bone and titanium alloy strengths. In conclusion, from a biomechanical point of view, PDs appear to be viable alternatives for rehabilitating severe atrophic maxillae.