Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. METHODS: To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC's therapeutic effects on chondrocytes. RESULTS: The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1ß, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. CONCLUSIONS: This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC's comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC's therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.

The Effects of Maca (Lepidium meyenii Walp) on Cellular Oxidative Stress: A Systematic Review and Meta-Analysis.

Lepidium meyenii Walp (LmW) or Maca, including its bioactive components such as macamides, among others, has demonstrated antioxidant effects. However, the effect size (ES) of LmW on oxidative stress has not been qualitatively described and calculated. The primary objective of this systematic review and meta-analysis was to review and qualitatively describe the studies published up to 2023 that supplemented LmW to control cellular oxidative stress; the secondary objective was to calculate the ES of the different interventions. The search was designed following the PRISMA® guidelines for systematic reviews and meta-analyses and performed in the Web of Science, Scopus, SPORTDiscus, PubMed, and MEDLINE until 2023. The selection of studies included randomized controlled trials, with tests and post-tests, both in vitro and in vivo in animals and humans. The methodological quality and risk of bias were evaluated with the CAMARADES tool. The main variables were reduced glutathione, glutathione peroxidase, superoxide dismutase, and malondialdehyde. The analysis was conducted with a pooled standardized mean difference (SMD) through Hedges' g test (95% CI). Eleven studies were included in the systematic review and eight in the meta-analysis. They revealed a small effect for reduced glutathione (SMD = 0.89), a large effect for glutathione peroxidase (SMD = 0.96), a moderate effect for superoxide dismutase (SMD = 0.68), and a moderate effect for malondialdehyde (SMD = -0.53). According to the results, the phytochemical compounds of LmW effectively controlled cellular oxidative stress, mainly macamides. It was also determined that a higher dose of LmW generated a greater antioxidant effect. However, information concerning humans is scarce.

The impact of photobiomodulation on angiogenic differentiation of two different dental derived stem cells using two irradiation protocols: an in vitro investigation.

The present study aimed to compare the effect of photobiomodulation with different energy densities on the angiogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and stem cells from human exfoliated deciduous teeth (SHED). Photobiomodulation therapy with a 660 nm diode laser (2.4 J/cm2 and 3.9 J/cm2) on two consecutive days post-culture was applied to two types of stem cells (hPDLSCs and SHED). The Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) test was undertaken to investigate Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin I (ANG-I) genes on days 1, 3, 5, 7, and 10 after the first session of laser application. The 4',6-diamidino-2-phenylindole (DAPI) staining and Methyl Thiazolyl Tetrazolium (MTT) test were conducted on days 1, 3, and 5 after the first session of laser application, to assess the cell viability. The Two-way ANOVA with Tukey post hoc test was used to analyze the outcomes of the MTT and RT-qPCR tests. The results of the MTT and DAPI convergently illustrated that the groups receiving photobiomodulation with 2.4 J/cm2 had higher cell viability compared to 3.9 J/cm2. All experimental groups showed an upregulation of VEGF-A and ANG-I gene expression from day 1 to 5, followed by a downregulation from day 5 to 10. The groups with cultured hPDLSCs and SHED receiving photobiomodulation using 2.4 J/cm2 had the most amounts of VEGF-A and ANG-I gene expression on day 5, respectively. In conclusion, the 660 nm mediated photobiomodulation therapy of cultured SHED and hPDLSCs with 2.4 J/cm2 energy density may be associated with higher angiogenic differentiation (the expression of VEGF-A and ANG-I) as well as higher cell viability compared to the photobiomodulation therapy with 3.9 J/cm2.

Experimental Protocols Used to Mimic Gastrointestinal Protein Digestion: A Systematic Review.

Bioactive peptides derived from native proteins modulate physiological processes in the metabolic pathways. Given that multiple protocols in the literature mimic the digestion of dietary components, gathering studies that use such models directed at protein digestion processes is critical. This systematic review aimed to gather evidence that adopted adequate experimental models to simulate human protein digestion. The databases searched were PubMed, Web of Science, ScienceDirect, Embase, Virtual Health Library, and Scopus. A total of 1985 articles were found, resulting in 20 eligible in vitro studies. The Office of Health Assessment and Translation was used to evaluate methodological quality. Seven studies used plant-based protein sources, twelve used animal protein sources, and one used both. The duration of the oral phase varied, although 60% of the studies employed a protein digestion period of 120 min. Amylase, pepsin, and pancreatin enzymes were utilized in 40% of the studies, with pH levels of 7, 3, and 7, respectively, during the oral, gastric, and intestinal phases. The INFOGEST harmonized static model was adopted by 65% of the studies; INFOGEST is the most effective model for simulating gastrointestinal protein processes in humans and can be used to answer several research questions because it describes experimental conditions close to the human physiological situation.

Engineered 3D Periodontal Ligament Model with Magnetic Tensile Loading.

In vitro models are invaluable tools for deconstructing the biological complexity of the periodontal ligament (PDL). Model systems that closely reproduce the 3-dimensional (3D) configuration of cell-cell and cell-matrix interactions in native tissue can deliver physiologically relevant insights. However, 3D models of the PDL that incorporate mechanical loading are currently lacking. Hence, we developed a model where periodontal tissue constructs (PTCs) are made by casting PDL cells in a collagen gel suspended between a pair of slender, silicone posts for magnetic tensile loading. Specifically, one of the posts was rigid and the other was flexible with a magnet embedded in its tip so that PTCs could be subjected to tensile loading with an external magnet. Additionally, the deflection of the flexible post could be used to measure the contractile force of PDL cells in the PTCs. Prior to tensile loading, second harmonics generation analysis of collagen fibers in PTCs revealed that incorporation of PDL cells resulted in collagen remodeling. Biomechanical testing of PTCs by tensile loading revealed an elastic response at 4 h, permanent deformation by 1 d, and creep elongation by 1 wk. Subsequently, contractile forces of PDL cells were substantially lower for PTCs under tensile loading. Immunofluorescence analysis revealed that tensile loading caused PDL cells to increase in number, express higher levels of F-actin and α-smooth muscle actin, and become aligned to the tensile axis. Second harmonics generation analysis indicated that collagen fibers in PTCs progressively remodeled over time with tensile loading. Gene expression analysis also confirmed tension-mediated upregulation of the F-actin/Rho pathway and osteogenic genes. Our model is novel in demonstrating the mechanobiological behavior that results in cell-mediated remodeling of the PDL tissue in a 3D context. Hence, it can be a valuable tool to develop therapeutics for periodontitis, periodontal regeneration, and orthodontics.

The role of light emitting diode in wound healing: A systematic review of experimental studies.

Wounds represent a growing global issue demanding increased attention. To expedite wound healing, technologies are under development, and light emitting diode (LED) devices of varying wavelengths are being explored for their stimulating influence on the healing process. This article presents a systematic literature review aiming to compile, organize, and analyze the impacts of LED devices on wound healing. This review is registered on the PROSPERO platform [CRD42023403870]. Two blinded authors conducted searches in the Pubmed, Web of Science, Scopus, Embase, and ScienceDirect databases. In vitro and in vivo experimental studies assessing LED utilization in the wound healing process were included. The search yielded 1010 studies, of which 27 were included in the review. It was identified that LED stimulates different healing pathways, promoting enhanced cell proliferation and migration, angiogenesis stimulation, increased collagen deposition, and modulation of the inflammatory response. Thus, it can be concluded that the LED stimulates cellular and molecular processes contingent on the utilized parameters. The effects depend on the standards used. Cell migration and proliferation were better influenced by green and red LED. The extracellular matrix components and angiogenesis were regulated by all wavelengths and the modulation of inflammation was mediated by green, red, and infrared LEDs.

The moral obligation to have genetically related children.

Donor conceived persons are likely to have a lower quality of life than persons who are genetically related to both parents. Empirical evidence is presented to corroborate this point. The evidence is subdivided into three sections: (1) negative experience of the donor conception itself, (2) negative effects of secrecy and openness and (3) negative effects of donor anonymity and donor identifiability. The principle of procreative beneficence requires parents to select the child with the best possible life. Given the difference in quality of life, intended parents should try to have a genetically related child. This finding is also a strong reason for society to invest public resources in the development of techniques that enable people to create genetically related children.

Açaí juice stains a glazed resin-modified glass-ionomer cement.

Coloured compounds (anthocyanins) in açaí can stain resin-modified glass-ionomer cement (RMGIC) due to its low staining resistance. AIM: The aim of this study was to assess whether açaí compromises the surface colour and roughness of RMGIC in vitro. MATERIALS AND METHOD: Disc-shaped specimens (2 mm thick, 8 mm in diameter) of Vitremer™ (3M ESPE, St Paul, MN, USA) were prepared according to the manufacturer 's instructions. The mixture was inserted into a silicone mouldplaced between two mylar strips, and light cured. Specimens were randomly divided into three groups (n=25) according to the solutions to be used for chemical degradation: artificial saliva (control), açaí sorbet and açaí juice. A spectrophotometer CM-2600d/2500d (Konica Minolta, Tokyo, Japan) was used to analyse the colour (CIELa*b* scale). Surface roughness (Ra, mm) was measuredusing theprofilometer Surfcorder SE 1700 (Kosaka Corp, Tokyo, Japan). The specimens were subjected to three daily soaks (6 ml, 15 minutes) for 14 days at 37°C. They were washed in distilled water and placed in fresh saliva (30 minutes in the interval). After the third soak in a day, they were stored in fresh saliva overnight. Outcomes were analysed at baseline (L*, a*, b*, Ra) and after degradation (L'*, a'*, b'*, Ra'). RESULTS: The pH values of saliva, sorbet, and juice were 7.0, 3.8, and 4.9, respectively. ΔE* values were 6.6 for saliva, 6.9 for sorbet and 7.8 for juice. There was a significant ΔE* difference between saliva (p=0.005) and juice (p=0.002), and between juice and sorbet (p=0.019), but none between saliva and sorbet (p=0.401). There was no significant Δb* difference between the solutions. No difference between juice and sorbet was observed for Δa*, but they were significantly different from saliva (p<0.001). Brightness (L*) changed significantly. Juice showed the highest ΔE* (7.8) and ΔL* (7.7). No significant change was observed for roughness and there was no difference between the solutions for ARa. CONCLUSIONS: Açaí and saliva led to unacceptable staining, but no significant roughness changes in the resin-modified glass-ionomer cement.

As antocianinas presentes no açaí podem manchar o cimento de ionomero de vidro modificado por resina (CIVMR) devido a baixa resistencia ao manchamento do material. OBJETIVO: O objetivo desse estudo foi avaliar se o açaí compromete a cor e a rugosidade de superficie de um CIVMR in vitro. MATERIAIS E MÉTODOS: Amostras (2 mm de espessura, 8 mm de diámetro) de Vitremer™ (3M ESPE, St Paul, MN, USA) foram preparadas de acordo com as instrugoes do fabricante. O materialfoi espatulado, inserido em um molde de silicone colocado entre duas tiras de poliestireno e fotopolimerizado. Após, as amostras foram randomizadas e alocadas em tres grupos (n=25) de acordo com as solugoes usadas para a degradagao química: saliva artificial (controle) e sorbet de açaí e suco de açaí. Utilizou-se o espectrofotometro CM-2600d/2500d (Konica Minolta, Tokyo, Japan) para a análise da cor (escala CIELa*b*) e o rugosímetro Surfcorder SE 1700 (Kosaka Corp, Tokyo, Japan) para a rugosidade de superficie (Ra, mm). As amostras foram submetidas a tres imersoes diárias (6 ml, 15 minutos) em cada solugao por 14 dias a 37°C, tendo sido lavadas em água destilada e mantidas em saliva fresca (30 minutos) nos intervalos. Após a terceira imersao no dia, as amostras foram mantidas em saliva renovada até o dia seguinte. As variáveis foram analisadas antes (L*, a*, b*, Ra) e depois da degradagao química (L'*, a'*, b'*, Ra'). RESULTADOS: Os valores de pH da saliva, sorbet e suco foram, respectivamente 7,0, 3,8 e 4,9. Houve diferenga significante para ΔE* entre saliva (p=0.005) e suco (p=0.002) e entre suco e sorbet (p=0.019), mas nao entre saliva e sorbet (p=0.401). Nao foi observada diferenga significante para Δb* entre as solugoes. Nao houve diferenga significante para Δa* entre suco e sorbet, mas eles foram significativamente diferentes da saliva (p<0.001). A luminosidade (L*) mostrou alteragao significante. O suco mostrou os maiores valores de ΔE* (7,8) e ΔL* (7,7)". Nao houve mudanga significante para a rugosidade e nao foi observada diferenga significante entre as solugoes para ARa (p>0.05). CONCLUSÃO: O açaí e a saliva causaram manchamento inaceitável do glaze do CIVMR e insignificante alteragao da rugosidade.

Comparative in vitro evaluation of microgap in titanium stock versus cobalt-chrome custom abutments on a conical connection implant: Effect of crown cementation and ceramic veneering.

OBJECTIVE: To compare the implant-abutment connection microgap between computer-aided design and computer-aided manufacturing (CAD/CAM) milled or laser-sintered cobalt-chrome custom abutments with or without ceramic veneering and titanium stock abutments with or without crown cementation. MATERIAL AND METHODS: Six groups of six abutments each were prepared: (1) CAD/CAM cobalt-chrome custom abutments: milled, milled with ceramic veneering, laser-sintered, and laser-sintered with ceramic veneering (four groups: MIL, MIL-C, SIN, and SIN-C, respectively) and (2) titanium stock abutments with or without zirconia crown cementation (two groups: STK and STK-Z, respectively). Abutments were screwed to the implants by applying 30 Ncm torque. All 36 samples were sectioned along their long axes. The implant-abutment connection microgap was measured using scanning electron microscopy on the right and left sides of the connection at the upper, middle, and lower levels. Data were analyzed using the Kruskal-Wallis test (p < .05). RESULTS: Mean values (µm) of the microgap were 0.54 ± 0.44 (STK), 0.55 ± 0.48 (STK-Z), 1.53 ± 1.30 (MIL), 2.30 ± 2.2 (MIL-C), 1.53 ± 1.37 (SIN), and 1.87 ± 1.8 (SIN-C). Although significant differences were observed between the STK and STK-Z groups and the other groups (p < .05), none were observed between the milled and laser-sintered groups before or after ceramic veneering. The largest microgap was observed at the upper level in all groups. CONCLUSIONS: Titanium stock abutments provided a closer fit than cobalt-chrome custom abutments. Neither crown cementation nor ceramic veneering resulted in significant changes in the implant-abutment connection microgap.

A feasible in vitro method to evaluate bacterial infiltration in three implant-abutment connection systems / Método in vitro factible para evaluar la infiltración bacteriana en tres sistemas de conexión implante-pilar

Introduction: Microorganism infiltration through the im-plant-abutment interface causes oral health problems such as periimplantitis, leading to implant loss. Materials and Methods: A feasible new method to quantify the Streptococcus mutans (S. mutans) infiltration through the implant-abutment interface gap is introduced in the present work. Internal hexagon (IH; n = 10), external hexagon (EH; n = 10), Morse taper (MT; n = 10), and a control for each group (n = 1) were tested. Bacteria suspension was prepared at 1.5x108 CFU/mL (CFU: colony forming units), and the implants were individually submerged up to the connection level, allowing the bacteria to contact it. The abutment was removed, and bacteria count was performed. Results: The implant sets were tested under normal bacterial growth and early and late biofilm growth conditions. Colony-forming units per mL were obtained, and the results were compared among groups. Differences in bacterial count between the MT and EH (p<0.001) and the MT and IH (p<0.001) groups were significantly higher in the MT-type implant. There was a significant increment of bacterial infiltration in the MTs submitted to late biofilm growth conditions. EH and IH connections are more effective in preventing bacterial infiltration independent of the growth condition. Conclusions: The proposed methodology is feasible to evaluate the infiltration of microorganisms through the implant-abutment interface.

Introducción: La infiltración de microorganismos a través de la interfaz implante-pilar provoca problemas de salud bucal como la periimplantitis, que conduce a la pérdida del implante. Materiales y Métodos: En el presente trabajo se presenta un nuevo método factible para cuantificar la infiltración de Streptococcus mutans (S. mutans) a través de la brecha de la interfaz implante-pilar. Se probaron el hexágono interno (IH; n = 10), el hexágono externo (EH; n = 10), el cono Morse (MT; n = 10) y un control para cada grupo (n = 1). Se preparó una suspensión de bacterias a 1,5x108 UFC/mL y los implantes se sumergieron individualmente hasta el nivel de conexión, permitiendo que las bacterias entraran en contacto con él. Resultados: Se retiró el pilar y se realizó recuento de bacterias. Los conjuntos de implantes se probaron en condiciones de crecimiento bacteriano normal y de crecimiento temprano y tardío de biopelículas. Se obtuvieron unidades formadoras de colonias por ml y los resultados se compararon entre grupos. Las diferencias en el recuento bacteriano entre los grupos MT y EH (p<0,001) y MT e IH (p<0,001) fueron significativamente mayores en el implante tipo MT. Hubo un incremento significativo de la infiltración bacteriana en los MT sometidos a condiciones tardías de crecimiento de biopelículas. Las conexiones EH e IH son más efectivas para prevenir la infiltración bacteriana independientemente de las condiciones de crecimiento. Conclusión: La metodología propuesta es factible para evaluar la infiltración de microorganismos a través de la interfaz implante-pilar.

Influence of different opacities and layering technique of nanotechnology composite resins regarding the wavelength and fluorescence intensity: in vitro study / Influencia de diferentes opacidades y la técnica de estratificación de resinas compuestas de nanotecnología en la longitud de onda e intensidad de fluorescencia: estudio in vitro

Objective: To evaluate the influence of opacity and the layering technique on the fluorescence of different composite resins. Materials and Methods: Two opacities (enamel and dentin) and the layering technique (enamel + dentin) of the composite resins: Filtek® Z350 and Palfique LX5 were evaluated in vitro. Composite resin discs were fabricated using a preformed matrix of 10 mm diameter and 0.5 mm thick for the single opacity groups and 10 mm thick for the layering technique groups, using 2 layers of 0.5 mm thickness of each opacity (n = 5). Specimens were analyzed using the Raman spectroscopy method. Data were analyzed using the Kruskall-wallis and Mann-Whitney U tests. Results: When evaluating the intensity of fluorescence, no statistically significant difference was found when comparing the layering technique and enamel opacity (p2> 0.05) and an increase in the dentin opacity value for both brands of composite resin. Regarding wavelength, no statistically significant difference was found when comparing the layering technique with enamel opacity and dentin opacity for both Filtek® Z350 and Palfique LX5® composite resins (p2 > 0.05). Conclusions: The fluorescence intensity of the layering technique is similar to enamel opacity for both composite resins. Likewise, the wavelength of the layering technique is similar to the enamel opacity and dentin opacity for both brands.

Objetive: Evaluar la influencia de la opacidad y de la técnica de estratificación en la fluorescencia de diferentes resinas compuestas. Materiales y Métodos: Se evaluó in vitro 2 opacidades (Esmalte y Dentina) y la técnica de estratificación (Esmalte + Dentina) de las resinas compuestas: Filtek® Z350 y Palfique LX5. Se fabricaron discos de resina compuesta, utilizando una matriz preformada de 10 mm de diámetro y 0,5 mm de grosor para los grupos de opacidad única y 10 mm de grosor para los grupos de técnica estratificada, utilizando 2 capas de 0,5 mm de cada opacidad (n = 5). Los especímenes se analizaron mediante el método de Espectroscopía Raman. Los datos se analizaron utilizando la prueba de Kruskall-wallis y Prueba U de Mann Whitney. Resultado: Al evaluar la intensidad de fluorescencia no se encontró diferencia estadísticamente significativa entre los pares: Técnica estratificada versus Opacidad Esmalte para ambas marcas de resina compuesta Filtek® Z350 y para Palfique LX5® (p2 > 0,05). Para longitud de onda no se encontró diferencia estadísticamente significativa entre los pares: Técnica estratificada versus Opacidad Esmalte y Técnica estratificada VS Opacidad Dentina para ambas resinas compuesta Filtek® Z350 y Palfique LX5® (p2> 0,05). Conclusión: La intensidad de fluorescencia de la técnica estratificada es similar a la opacidad Esmalte para ambas resinas compuestas. De igual manera la longitud de onda de la técnica estratificada es similar a la opacidad Esmalte y opacidad Dentina para ambas marcas.

'Recombining' biological motherhoods. Towards two 'complete' biological mothers.

Within feminist literature from the early 1970s to this day, assisted reproductive technologies have been largely known to divide, replace or eliminate biological motherhood. For example, while in the past biological motherhood was considered a continuous experience, in vitro fertilisation (IVF) and IVF using egg donation allowed a split between two biological mothers, one providing eggs (genetic mother) and the other one gestation (gestational mother). This split was considered irreparable: the genetic mother could not be also gestational, and vice versa. On the contrary, this paper aims to show that assisted reproductive technologies may also have a constructive potential towards biological motherhood(s). To explain how it could be possible, two existing techniques are explored: the first is maternal spindle transfer, which allows a double genetic motherhood; the second is reciprocal effortless IVF, which supposedly enables a double gestational motherhood. While in the first part, these techniques are examined singularly, in the second part a feasible combination of them is speculated. The idea is that assisted reproductive technologies could 'recombine' genetic and gestational motherhood in two figures that include both, namely in two 'complete' biological mothers, both genetic and gestational.

Efficiency of cavitary varnishes containing experimental bioglass particles in the occlusion of dentinal tubules.

This research aims to evaluate the efficiency of cavitary varnishes containing experimental bioglasses in the occlusion of dentinal tubules. One hundred and sixty-eight cervical buccal dentin samples were obtained from bovine teeth. Samples were randomized into the following groups: I. Distilled Water (DW); II. Cavity Varnish (CV); III. Colgate® Sensitive Pro-Relief™ (CS); IV. 45S5 Bioglass (45S5); V. KSr Bioglass strontium potassium (KSr); VI. P Bioglass phosphorus (P); and VII. PSi Bioglass phosphorus silica (PSi). The treatments were applied to the surfaces of the samples, which were then subjected to simulated brushing. The samples were analyzed for a) characterization of bioactive glasses; b) surface roughness; c) descriptive analysis of the dentin surface; d) total versus occluded number of dentinal tubules; e) diameter of the dentinal tubules; f) chemical composition of the dentin surfaces, and g) dentin permeability. All groups treated with biomaterials without the brushing challenge showed an increase in roughness and (total or partial) occlusion of the dentinal tubules. The PSi group had the best values for occlusion, while the KSr group had the highest calcium and phosphorus concentrations. After the brushing challenge the roughness was controlled by the presence of biomaterials; 45S5, KSr, and PSi showed occlusion of the dentin tubules. All bioactive glasses showed reduced tooth permeability compared to distilled water. The PSi group had the smallest tubule diameter and highest phosphorus concentration. KSr and PSi bioglasses are promising materials for dentin occlusion and remineralization and are promising new biomaterials for the treatment of dentin hypersensitivity.

Experimental comparison of first-pass effect between direct thromboaspiration and combined thrombectomy in the setting of distal basilar occlusion.

BACKGROUND: Studies investigating endovascular therapy in vertebro-basilar stroke have led to controversial results in the past, but recent randomized trials seem to show an effectiveness superiority of endovascular therapy versus best medical treatment. However, uncertainty remains concerning many aspects of thrombectomy in acute basilar artery occlusion, notably technical considerations. This study compared the first-pass effect of direct thromboaspiration and combined thrombectomy in the setting of distal basilar occlusion. METHODS: An in-vitro experimental set-up was used, consisting of a vascular phantom model and thrombus analogs of different consistencies to mimic human clots. Thrombus analogs were injected into the model through the vertebral artery and flowed to the basilar distal third to mimic a distal basilar occlusion. Ten procedures were performed for each thrombus analog stiffness and technique (direct thromboaspiration versus combined thrombectomy). RESULTS: Direct thromboaspiration showed an overall first-pass effect rate of 83.3% (25/30) and was particularly effective for ultra-soft and soft clot analogs, but decreased for hard clot analogs. Combined thrombectomy had an overall first-pass effect rate of 56.7% (17/30). The effect rate for ultra-soft and soft clot analogs was 60% and 50% for hard clot analogs. In the softer clot analogs, the stent-retriever device used for the combined thrombectomies tended to deviate the clot analog from a co-axial trajectory with the aspiration catheter. CONCLUSIONS: In the context of distal basilar occlusion, our in-vitro results showed that higher first-pass effect rates were achieved with direct thromboaspiration compared to combined thrombectomy in all types of thrombus analogs.

Factors related to vessel displacement due to stent retriever retraction: An in vitro study.

BACKGROUND: Thrombectomy with a stent retriever (SR) may lead to intracranial hemorrhage due to vessel displacement. We aimed to explore factors related to vessel displacement using an in vitro vessel model. METHODS: A vessel model mimicking two-dimensional left internal carotid angiography findings was used in this study. Six SR types (Solitaire 3 × 40, 4 × 40, and 6 × 40; Embotrap 5 × 37; Trevo 4 × 41; and Tron 4 × 40) were fully deployed in the M2 ascending, M2 bend, or M1 horizontal portion. Subsequently, the SR was retracted, and the vessel displacement, maximum SR retraction force, and angle of the M2 bend portion were measured. A total of 180 SR retraction experiments were conducted using 6 SR types at 3 deployment positions with 10 repetitions each. RESULTS: The mean maximum distance of vessel displacement for Embotrap Ⅲ 5 × 37 (6.4 ± 3.5 mm, n = 30) was significantly longer than that for the other five SR types (p = 0.029 for Solitaire 6 × 40 and p < 0.001 for the others, respectively). Vessel displacement was significantly longer in the M2 ascending portion group (5.4 ± 3.0 mm, n = 60) than in the M2 bend portion group (3.3 ± 1.6 mm, n = 60) (p < 0.001) and it was significantly longer in the M2 bend portion group than in the M1 horizontal portion group (1.1 ± 0.7 mm, n = 60) (p < 0.001). A positive correlation existed between the mean maximum SR retraction force or mean angle of the M2 bend portion due to SR retraction (i.e., vessel straightening) and the mean maximum distance of vessel displacement (r = 0.90, p < 0.001; r = 0.90, p < 0.001, respectively). CONCLUSIONS: Vessel displacement varied with the SR type, size, and deployment position. Moreover, vessel displacement correlated with the SR retraction force or vessel straightening of the M2 bend portion.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Friction injury of the central vein caused by catheter for hemodialysis: an in vitro study.

Vascular injury such as central venous stenosis (CVS) is a common complication in hemodialysis patients with central venous catheters (CVCs), yet the impact of the microstructure and partial physic characteristics of catheter surface on the chronic injury of central vein has not been elucidated. In this study, the microscopic morphology of tips and bodies of six different brands of polyurethane CVCs was observed and their roughness was assessed. Subsequently, an in vitro model was established to measure the coefficients of friction (COF) between CVCs (tips and bodies) and the vena cava intima of Japanese rabbits under the same condition in a linear reciprocating mode, and changes in the intima of vessels after friction were observed. The study found that there was a significant variation in surface roughness among different brands of CVCs (tips P < 0.001, bodies P = 0.02), and the COF was positively correlated with the catheter surface roughness (tips P = 0.005, R = 0.945, bodies P = 0.01, R = 0.909). Besides, the endovascular roughness increased after friction. These findings suggest that the high roughness surface of CVCs may cause chronic mechanical friction injury to the central venous intima, which is one of the potential factors leading to CVS or occlusion. This provides a breakthrough for reducing complications, improving patient prognosis, and advancing catheter surface lubrication technology.

Evaluation of cellular viability in chitosan/L-arginine hydrogels.

BACKGROUND: There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety. OBJECTIVES: This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine. MATERIAL AND METHODS: The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05. RESULTS: In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data. CONCLUSIONS: Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.