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1.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982421

RESUMO

The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram- or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either gram- or gram+ bacterial pathogens or their purified membrane components (LPS and LTA) results in the activation of NF-κB, apoptosis-regulating kinase1 (ASK1), and MAP kinase signaling pathways including, c-Jun N-terminal kinase (JNK) and p38 together with their physiological substrates AP-1 and ATF-2, respectively. Inhibition of S100A15 by antibodies-mediated Toll-like receptor 4 (TLR4) or Toll-like receptor 2 (TLR2) neutralization reveals the induction of S100A15 protein by LPS/gram- bacterial pathogens to be TLR4- dependent mechanism, whereas induction by LTA/gram+ bacterial pathogens to be TLR2- dependent mechanism. Pre-treatment of GF and KB cells with JNK (SP600125), p38 (SB-203580), or NF-κB (Bay11-7082) specific inhibitors further demonstrates the importance of JNK, p38 and NF-κB pathways in the regulation of gram-/gram+ bacterial pathogen-induced S100A15 expression. Our data provide evidence that S100A15 is induced in cancer and non-cancer oral mucosa-derived cell lines by gram-/gram+ bacterial pathogens and provide insight into the molecular mechanisms by which gram- and gram+ bacterial pathogens induce S100A15 expression in the oral mucosa.


Assuntos
Anti-Infecciosos , NF-kappa B , Humanos , Anti-Infecciosos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like , Receptores Toll-Like
2.
Int J Mol Sci ; 23(4)2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35216181

RESUMO

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.


Assuntos
Candidíase Bucal/tratamento farmacológico , Cromogranina A/farmacologia , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Animais , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/metabolismo , Candidíase Bucal/metabolismo , Bovinos , Farmacorresistência Fúngica/efeitos dos fármacos , Humanos , Soroalbumina Bovina/metabolismo
3.
Clin Oral Investig ; 25(6): 3757-3765, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33244706

RESUMO

OBJECTIVES: The aim of this study was to assess the filling quality of five obturation techniques in oval-shaped root canals. MATERIALS AND METHODS: A total of 212 mandibular first molars with one distal oval canal were selected. Distal canals, shaped with WaveOne Gold Primary, were randomly divided in five groups (n = 40) for obturation: continuous wave condensation, GuttaCore, Thermafil, single cone with AH plus, and single cone with BioRoot RCS. The proportions of gutta-percha-filled areas (GPFA), sealer-filled areas (SFA), void areas (VA), and the sealer/gutta tags into dentinal tubules at 4 mm and 2 mm from the apex were analyzed by an optical numeric microscope, SEM, and energy-dispersive X-ray (EDX). Data were then compared by Kruskal-Wallis one-way ANOVA on ranks (α = 0.05). RESULTS: At 4 mm, a statistically significant higher GPFA and lower SFA were observed in the GuttaCore and Thermafil groups compared with the 3 other groups. A statistically significant lower VA was observed in the continuous wave condensation, GuttaCore, and Thermafil groups than in the two single-cone groups. At 2 mm, there were a statistically significant higher GPFA and lower SFA and VA in GuttaCore and Thermafil groups than in the 3 other groups. At the two levels investigated, the presence of gutta-percha tags was clearly demonstrated for GuttaCore and Thermafil groups; no tags were observed in the 3 other groups. CONCLUSIONS: Obturation quality was overall improved in GuttaCore and Thermafil groups. CLINICAL RELEVANCE: Carrier-based techniques may significantly improve the filling quality compared to continuous wave condensation and single-cone technique. The single-cone technique might have inherent limitations especially in oval root canals regardless of the sealer used.


Assuntos
Materiais Restauradores do Canal Radicular , Obturação do Canal Radicular , Cavidade Pulpar , Guta-Percha , Preparo de Canal Radicular
4.
Medicina (Kaunas) ; 57(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34833377

RESUMO

There are a number of potential implications for the field of Alzheimer's disease (AD) stemming from the global spread of "SARS-COV-2". Many studies that were conducted by Cleveland Clinic researchers identified a link between COVID-19 infection and brain abnormalities seen in people with AD. This article explains the association between COVID-19 and AD and how people with AD are affected by COVID-19, whether directly or indirectly. First, this article begins by explaining AD and its types, then giving an overview about COVID-19, its symptoms and the associated complications. Then, direct and indirect consequences of COVID-19 on people experiencing AD are discussed briefly. Some management strategies are recommended at the end of this article in addition to a future perspective on this topic. This article concludes by summarizing the main points mentioned about the association between COVID-19 and AD.


Assuntos
Doença de Alzheimer , COVID-19 , Doença de Alzheimer/epidemiologia , Humanos , SARS-CoV-2
5.
J Contemp Dent Pract ; 21(10): 1117-1121, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33686032

RESUMO

AIM: The aim of this in vitro research was to study the effect of etching by phosphoric acid with rubbing technique on the shear bond strength (SBS) of adhesive universal to enamel. MATERIALS AND METHODS: Sixty extracted teeth were obtained. Three application methods (self-etch, etch-and-rinse, and etch-and-rinse with rubbing technique) were performed to bond the enamel surfaces by a universal adhesive. After 24 hours of immersion in water at 37°C, the specimens were prepared for the SBS test. Scanning electron microscopy was performed to observe the adhesive-enamel interfaces. Optical numeric microscope was used to observe the failure style. Statistical analyses were done with one-way analysis of variance test. RESULTS: Statistically significant higher bond strength values were observed for etch-and-rinse mode with rubbing technique (25.98 ± 5.70) MPa then for the etch-and-rinse without rubbing (22.07 ± 5.27) MPa and self-etch modes (9.96 ± 2.98) MPa. CONCLUSION: Enamel etched by 37% phosphoric acid with rubbing technique for 20 seconds showed an increase in the SBS of the universal adhesive to enamel surfaces. The tags of the adhesive can be presented more efficiently by rubbing the acid before the bonding process, consequently, an optimal interface for the bonding. CLINICAL SIGNIFICANCE: According to the results of this in vitro study, the selective enamel etching mode with rubbing technique is advisable when using the universal adhesive, as it significantly increased the bond strength of this adhesive to enamel surfaces. The clinician should etch the enamel using phosphoric acid with rubbing technique for 20 seconds to promote the bond strength of the universal adhesive system.


Assuntos
Colagem Dentária , Adesivos Dentinários , Condicionamento Ácido do Dente , Cimentos Dentários , Esmalte Dentário , Teste de Materiais , Ácidos Fosfóricos , Cimentos de Resina , Resistência ao Cisalhamento
6.
Lab Invest ; 99(4): 539-550, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30446717

RESUMO

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.


Assuntos
Centro Germinativo/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Linhagem Celular , Humanos , Imuno-Histoquímica , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/genética , Transfecção
7.
J Contemp Dent Pract ; 20(8): 915-919, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31797847

RESUMO

AIM: The purpose of this study was to evaluate the microscopic and chemical effects of phosphoric acid gel, phosphoric acid liquid, and polyacrylic acid application for 15 seconds (s) on coronal dentin. MATERIALS AND METHODS: Twelve extracted teeth were selected. Three etching acids were used to prepare the dentin surfaces. Scanning electron microscopy (SEM) and X-ray energy dispersive spectroscopy (EDX) were used to analyze the chemical and morphological changes of the dentinal surfaces, including the depth of demineralization. Collected data were statistically analyzed by the one-way analysis of variance test. RESULTS: Dentin etched with phosphoric acid gel or liquid showed greater peritubular dentin dissolution, including complete removal of the smear layer. In addition, there were many silica particles on the dentin etched by phosphoric acid gel 37%. The dentin that was etched with 25% polyacrylic acid for 15 seconds showed no smear layer removal. Chemical analysis (EDX) showed that dental surfaces etched with phosphoric acid liquid 37% for 15 seconds showed the strongest mineral dissolution at the calcium surface, with a calcium content of 5.25%. On the other hand, EDX analysis of the dental surface etched with 25% polyacrylic acid showed more surface enrichment in calcium (17.19%). CONCLUSION: Although phosphoric acid (gel or liquid) 37% cleans the dental surface, phosphoric acid gel precipitates silica particles on the etched dentin surface. These particles cannot be removed by rinsing off this acid. The application of polyacrylic acid for 15 seconds does not noticeably demineralized dentin, nor remove the smear layer. CLINICAL SIGNIFICANCE: The clinician should use phosphoric acid (gel or liquid) to clean dental surfaces to prepare them for the bonding process. The low demineralizing effects of the polyacrylic acid permits its use near the pulp.


Assuntos
Colagem Dentária , Camada de Esfregaço , Condicionamento Ácido do Dente , Dentina , Adesivos Dentinários , Humanos , Microscopia Eletrônica de Varredura , Ácidos Fosfóricos , Propriedades de Superfície
8.
J Cell Mol Med ; 20(2): 266-86, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26578344

RESUMO

Melanoma is characterized by dysregulated intracellular signalling pathways including an impairment of the cell death machinery, ultimately resulting in melanoma resistance, survival and progression. This explains the tumour's extraordinary resistance to the standard treatment. Imiquimod is a topical immune response modifier (imidazoquinoline) with both antiviral and antitumour activities. The mechanism by which imiquimod triggers the apoptosis of melanoma cells has now been carefully elucidated. Imiquimod-induced apoptosis is associated with the activation of apoptosis signalling regulating kinase1/c-Jun-N-terminal kinase/p38 pathways and the induction of endoplasmic stress characterized by the activation of the protein kinase RNA-like endoplasmic reticulum kinase signalling pathway, increase in intracellular Ca(2+) release, degradation of calpain and subsequent cleavage of caspase-4. Moreover, imiquimod triggers the activation of NF-κB and the expression of the inhibitor of apoptosis proteins (IAPs) such as, X-linked IAP (XIAP) together with the accumulation of reactive oxygen species (ROS). Also, imiquimod triggers mitochondrial dysregulation characterized by the loss of mitochondrial membrane potential (Δψm), the increase in cytochrome c release, and cleavage of caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP). Inhibitors of specific pathways, permit the elucidation of possible mechanisms of imiquimod-induced apoptosis. They demonstrate that inhibition of NF-kB by the inhibitor of nuclear factor kappa-B kinase (IKK) inhibitor Bay 11-782 or knockdown of XIAP induces melanoma apoptosis in cells exposed to imiquimod. These findings support the use of either IKK inhibitors or IAP antagonists as adjuvant therapies to improve the effectiveness topical imiquimod in the treatment of melanoma.


Assuntos
Aminoquinolinas/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Melanoma/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Cálcio/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Imiquimode , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Melanoma/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
9.
Eur J Dent ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029907

RESUMO

OBJECTIVES: The purpose of the present study was to investigate the created roughness and cell attachment of intact teeth (C), obturated teeth with bioceramic (BR), or epoxy resin (AH) after root resection using piezoelectric ultrasonic and carbide bur. MATERIALS AND METHODS: Three groups of first mandibular premolars were used in the present study: control group (without any preparation or obturation) (C); second group was obturated with an epoxy resin sealer (AH, AH Plus Jet); and finally, the third one was obturated with a bioceramic sealer (BR, BioRoot RCS). All teeth were incubated for 4 months at 37°C. After that, the samples were sectioned using tungsten carbide bur or piezoelectric ultrasonic. Roughness and then cell attachment of periodontal ligament cells on the sectioned surfaces were investigated by profilometer and confocal microscope, respectively. STATISTICAL ANALYSIS: Data were statistically analyzed using one-way analysis of variance. RESULTS: After root resection, no significant difference was found between the roughness among the three groups sectioned using the piezoelectric technique (p > 0.05). In contrast, concerning the sectioned samples by burs, C demonstrated a rougher surface compared with BR (p < 0.05). There was a significant higher cell attachment in BR compared with AH in the piezoelectric groups (p = 0.047), while no statistically significant difference was found between the groups sectioned with bur (p > 0.05). CONCLUSION: Dentists are now focused on the use of calcium silicate-based sealers due to their bioactivity. The present study advises dentists to use bioceramic sealer which could improve the dentin characteristics which ameliorate the cell attachment.

10.
Materials (Basel) ; 17(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38998454

RESUMO

The aim of the present in vitro study was to evaluate specific mechanical and physicochemical properties of three calcium silicate-based sealers, BioRoot™ Flow (BRF), CeraSeal (CRS) and TotalFill® (TF). Samples were prepared to evaluate different physicochemical and mechanical properties of the tested sealers. These evaluations were accomplished by investigating the pH changes over time, porosity, roughness, flow properties, compressive strength and wettability. The results were statistically evaluated using one-way analysis of variance. All three sealers demonstrated an alkaline pH from 1 h of immersion in water to 168 h. A higher porosity and hydrophily were detected in BRF samples compared to CRS and TF. No significant difference was found between the tested materials in the flow properties. Lower compressive strength values were observed for BRF compared to TF and CRS. Differently shaped structures were detected on the three materials after 7 days of immersion in PBS. The three materials demonstrated a higher solubility than 3% after 24 h of immersion in water (CRS < BRF < TF). The novel premixed calcium silicate sealer (BRF) had comparable physicochemical properties to the existing sealers. The lower compressive strength values could facilitate the removal of these materials during retreatment procedures. Further studies should investigate the biological effects of the novel sealer.

11.
Biomimetics (Basel) ; 9(4)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38667205

RESUMO

Solvent evaporation within an adhesive layer is a crucial step during a bonding process. The aim of this current research was to test whether the use of different air temperatures (20 °C, 40 °C, and 60 °C) for solvent evaporation improves the performance of four adhesive systems to dentin. Sixty non-carious human molar teeth were randomly prepared for micro-tensile bond strength (µTBS) tests. Four different adhesive systems, Prime&Bond Universal (PBU), OptiBond Universal (OBU), OptiBond FL (OBFL), and Clearfil SE (CSE), were applied following the manufacturer's instructions. Three groups based on the air-drying temperature were used: solvent evaporation was performed with either of warm (40 °C), (60 °C), and cold air as control group (20 °C) for 10 s at a distance of 5 cm. In all bonded surfaces, three resin composite (Reflectys, Itena Clinical, Paris, France) layers of 2 mm thickness were built up. The resin-dentin samples were kept in distilled water at 37 °C for 24 h and 6 months, respectively, before µTBS testing. Failure analysis, scanning electron microscopy of resin-dentin bonded interface, and solvent evaporation rate were tested as secondary variables. All analyses were conducted using a significance level of α = 0.05. Bond strength (BS) values were similar among all the adhesive systems used (p > 0.05). Also, the aging factor did not affect the BS (p > 0.05). Only the factor of temperature used for solvent evaporation resulted in a statistically significant effect (p < 0.05), with the temperature of 60 °C being the highest value (p < 0.05). A failure mode evaluation revealed mostly adhesive or mixed modes of failures in all the different temperatures of air used for the solvent evaporation of each adhesive system. The thickness of the adhesive layer and the creation of resin tags varied amongst the temperatures evaluated. For all adhesive systems tested, the use of 40 °C or 60 °C air for solvent evaporation led to an increased mass loss. Warmer temperatures for solvent evaporation contributed positively to bonding performance, enhancing both the quality of the adhesive layer and its interaction with the dentin tissue. Optimizing solvent evaporation with warmer air temperatures (40 °C and 60 °C) significantly improved µTBS, offering a practical means to enhance the quality and longevity of adhesive restorations in esthetic dentistry.

12.
Bioengineering (Basel) ; 11(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38534487

RESUMO

The present in vitro study focuses on the filling ability of three different bioceramic cements with or without the addition of a bioceramic sealer in an open apex model on the marginal apical adaptation, tubule infiltrations, and void distributions as well as the interface between the cement and the sealer materials. To this end, sixty mandibular premolars were used. MTA-Biorep (BR), Biodentine (BD), and Well-Root Putty (WR) were used to obturate the open apex model with or without the addition of a bioceramic sealer, namely TotalFill® BC sealer™ (TF). A digital optical microscope and scanning electron microscope (SEM) were used to investigate the cement-dentin interface, marginal apical adaptation, and the material infiltration into the dentinal tubules. Micro-computed X-ray tomography and digital optical microscopy were used to investigate the cement-sealer interface. The results were analyzed by using the Kruskal-Wallis test. No significant difference was found between the groups for the marginal apical adaptation quality (p > 0.05). Good adaptation of the dentin-cement interface was found for all tested groups and the sealer was placed between the cement material and dentinal walls. All the groups demonstrated some infiltrations into the dentinal tubules at the coronal part except for the BR group. A good internal interface was found between the cement and the sealer with the presence of voids at the external interface. A larger number of voids were found in the case of the BD-TF group compared to each of the other two groups (p < 0.05). Within the limitations of the present in vitro study, all the groups demonstrated good marginal apical adaptation. The use of a sealer in an open apex does not guarantee good filling and, in addition, creates voids at the external interfaces with the dental walls when the premixed sealer is used with powder-liquid cement systems. The use of a premixed bioceramic cement could offer fewer complications than when a powder-liquid cement system is used.

13.
Cancers (Basel) ; 16(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275910

RESUMO

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% of melanomas demonstrating the BRAF mutation (BRAFV600E). While the successful targeting of BRAFV600E does improve overall survival, the long-term efficacy of available therapeutic options is limited due to adverse side effects and reduced clinical efficacy. Additionally, drug resistance develops rapidly via mechanisms involving fast feedback re-activation of MAPK signaling pathways. This article updates information relevant to the mechanisms of melanoma progression and resistance and particularly the mechanistic role of CSCs in melanoma progression, drug resistance, and recurrence.

14.
Cells ; 13(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38334632

RESUMO

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed.


Assuntos
Melanoma , Sirolimo , Humanos , Sirolimo/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Melanoma/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Resistencia a Medicamentos Antineoplásicos
15.
J Proteome Res ; 12(8): 3667-78, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23834436

RESUMO

Staphylococcus aureus is responsible for severe bacterial infections in hospitals and healthcare facilities. It produces single and bicomponent toxins (leukotoxins and hemolysins) that hinder innate immune function. Leukotoxin subunits bind to leukocyte cell membrane thus inducing transmembrane pores and subsequently, cell lysis. Leukotoxin LukE/D is a member of the bicomponent toxin family, but to date, no study concerning its involvement in host-pathogen interactions has been reported. In the present study, we performed the proteomic analysis of the secretions recovered after activation of human neutrophils by leukotoxin LukE/D. The neutrophil secretions were purified by RP-HPLC and different fractions were analyzed by Edman sequencing, LC-MS/MS, immunoblotted for chromogranin-derived peptides and further analyzed for antimicrobial properties. Proteomic analysis revealed that neutrophil secretions constitute a large number of proteins related with immune boosting mechanisms, proteolytic degradation, inflammatory process and antioxidant reactions.


Assuntos
Exotoxinas/farmacologia , Neutrófilos/efeitos dos fármacos , Fragmentos de Peptídeos/análise , Proteoma/análise , Staphylococcus aureus/química , alfa-Defensinas/isolamento & purificação , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Cromatografia Líquida , Cromograninas/química , Exotoxinas/isolamento & purificação , Interações Hospedeiro-Patógeno , Humanos , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Anotação de Sequência Molecular , Neurospora crassa/efeitos dos fármacos , Neurospora crassa/crescimento & desenvolvimento , Neutrófilos/citologia , Neutrófilos/imunologia , Espectrometria de Massas em Tandem , alfa-Defensinas/farmacologia
16.
Apoptosis ; 18(8): 980-97, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23564313

RESUMO

Despite the availability of melanoma treatment at the primary site, the recurrence of local melanoma can metastasize to any distant organ. Currently, the available therapies for the treatment of metastatic melanoma are of limited benefit. Thus, the functional analysis of conventional therapies may help to improve their efficiency in the treatment of metastatic melanoma. In the present study, the exposure of melanoma cells to vinblastine was found to trigger apoptosis as evidenced by the loss of mitochondrial membrane potential, the release of both cytochrome c and apoptosis inducing factor, activation of caspase-9 and 3, and cleavage of Poly (ADP-ribose)-Polymerase. Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. In addition, vinblastine induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins. Moreover, inhibitory experiments addressed a central role for Rho A in the regulation of vinblastine-induced apoptosis of melanoma cells via mitochondrial and non-mitochondrial-dependent mechanisms. In conclusion, the present study addresses for the first time a central role for Rho A in the modulation of vinblastine-induced apoptosis of melanoma cells and thereby provides an insight into the molecular action of vinblastine in melanoma treatment.


Assuntos
Apoptose/efeitos dos fármacos , Melanoma/enzimologia , Mitocôndrias/metabolismo , Vimblastina/farmacologia , Proteína rhoA de Ligação ao GTP/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína rhoA de Ligação ao GTP/genética
17.
Langmuir ; 29(34): 10776-84, 2013 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-23895332

RESUMO

The design of films using a one-pot process has recently attracted increasing interest in the field of polymer thin film formation. Herein we describe the preparation of one-pot supramolecular polyrotaxane (PRX) films using the morphogen-driven self-construction process. This one-pot buildup strategy where the film growth is triggered by the electrochemical formation and diffusion of a catalyst in close vicinity of the substrate has recently been introduced by our group. A one-pot mixture was used that contained (i) poly(acrylic acid) (PAA) functionalized by azide groups grafted on the polymer chain through oligo(ethylene glycol) (EG) arms, leading to PAA-EG13-N3, (ii) cyclodextrins (α and ß CD), as macrocycles that can be threaded along EG arms, (iii) alkyne-functionalized stoppers (ferrocene or adamantane), to cap the PRX assembly by click chemistry, and (iv) copper sulfate. The one-pot mixture solution was brought into contact with a gold electrode. Cu(I), the morphogen, was generated electrochemically from Cu(II) at the electrode/one-pot solution interface. This electrotriggered click reaction leads to the capping of polypseudorotaxane yielding to PRXs. The PRXs can self-assemble through lateral supramolecular interactions to form aggregates and ensure the cohesion of the film. The film buildup was investigated using different types of CD and alkyne functionalized stoppers. Supramolecular PRX aggregates were characterized by X-ray diffraction measurements. The film topographies were imaged by atomic force microscopy. The influence of the concentration in CD and the presence of a competitor were studied as well. The stability of the resulting film was tested in contact with 8 M urea and during the electrochemical oxidation of ferrocene.


Assuntos
Ciclodextrinas/química , Eletroquímica/métodos , Poloxâmero/química , Rotaxanos/química , Química Click , Eletrodos , Microscopia de Força Atômica , Estrutura Molecular
18.
Bioengineering (Basel) ; 10(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36671627

RESUMO

Oral cavities provide an entry point for food and nutrients [...].

19.
Materials (Basel) ; 16(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37109947

RESUMO

The aim of the present study was to investigate the influence of the mechanical properties of three different calcium-silicate-based cements on the stress distribution of three different retrograde cavity preparations. Biodentine™ "BD", MTA Biorep "BR", and Well-Root™ PT "WR" were used. The compression strengths of ten cylindrical samples of each material were tested. The porosity of each cement was investigated by using micro-computed X-ray tomography. Finite element analysis (FEA) was used to simulate three retrograde conical cavity preparations with an apical diameter of 1 mm (Tip I), 1.4 mm (Tip II), and 1.8 mm (Tip III) after an apical 3 mm resection. BR demonstrated the lowest compression strength values (17.6 ± 5.5 MPa) and porosity percentages (0.57 ± 0.14%) compared to BD (80 ± 17 MPa-1.22 ± 0.31%) and WR (90 ± 22 MPa-1.93 ± 0.12%) (p < 0.05). FEA demonstrated that the larger cavity preparation demonstrated higher stress distribution in the root whereas stiffer cement demonstrated lower stress in the root but higher stress in the material. We can conclude that a respected root end preparation associated with cement with good stiffness could offer optimal endodontic microsurgery. Further studies are needed to define the adapted cavity diameter and cement stiffness in order to have optimal mechanical resistance with less stress distribution in the root.

20.
J Funct Biomater ; 14(5)2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37233396

RESUMO

Any excess solvent from dental adhesive systems must be eliminated prior to material photopolymerization. For this purpose, numerous approaches have been proposed, including the use of a warm air stream. This study aimed to investigate the effect of different temperatures of warm air blowing used for solvent evaporation on the bond strength of resin-based materials to dental and nondental substrates. Two different reviewers screened the literature in diverse electronic databases. In vitro studies recording the effect of warm air blowing to evaporate solvents of adhesive systems on the bond strength of resin-based materials to direct and indirect substrates were included. A total of 6626 articles were retrieved from all databases. From this, 28 articles were included in the qualitative analysis, and 27 remained for the quantitative analysis. The results of the meta-analysis for etch-and-rinse adhesives revealed that the use of warm air for solvent evaporation was statistically significantly higher (p = 0.005). For self-etch adhesives and silane-based materials, this effect was observed too (p < 0.001). The use of a warm air stream for solvent evaporation enhanced the bonding performance of alcohol-/water-based adhesive systems for dentin. This effect seems to be similar when a silane coupling agent is submitted to a heat treatment before the cementation of a glass-based ceramic.

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