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1.
Biomaterials ; 313: 122769, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39208698

RESUMO

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.


Assuntos
Materiais Revestidos Biocompatíveis , Matriz Extracelular , Cicatrização , Animais , Matriz Extracelular/metabolismo , Cães , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Cicatrização/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Reepitelização/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos
2.
Biointerphases ; 19(5)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39235276

RESUMO

In order to properly satisfy biomedical constraints for cardiovascular applications, additively manufactured NiTi scaffolds required further process and metallurgical engineering. Additively manufactured NiTi materials for cardiovascular use will have to undergo surface finishing in order to minimize negative surface interactions within the artery. In this study, we sought to understand biocompatibility from chemically etched additively manufactured NiTi scaffolds by laser powder bed fusion (LPBF). Although two distinct oxide films were created in the surface etching process (labeled CP-A and CP-B), no qualitative changes in microroughness were seen between the two conditions. CP-A possessed significantly less Ni at the surface (0.19 at. %) than the CP-B group (3.30 at. %), via x-ray photoelectron spectroscopy, alongside a concomitant shift in the O1 s peak presentation alluding to a greater formation of a Ni based oxide in the CP-B group. Our live dead staining revealed significant toxicity and reduced cellular attachment for the CP-B group, in addition to inducing more cell lysis (20.9 ± 5.1%), which was significantly increased when compared to CP-A (P < 0.01). Future practices of manufacturing NiTi scaffolds using LPBF should focus on producing surface films that are not only smooth, but free of cytotoxic Ni based oxides.


Assuntos
Materiais Biocompatíveis , Níquel , Propriedades de Superfície , Titânio , Titânio/química , Titânio/farmacologia , Níquel/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Óxidos/química , Óxidos/farmacologia , Teste de Materiais , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia Fotoeletrônica , Adesão Celular/efeitos dos fármacos , Alicerces Teciduais/química
3.
Commun Biol ; 7(1): 1131, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271940

RESUMO

Monocytes, the circulating macrophage precursors, contribute to diseases like atherosclerosis and asthma. Long non-coding RNAs (lncRNAs) have been shown to modulate the phenotype and inflammatory capacity of monocytes. We previously discovered the lncRNA SMANTIS, which contributes to cellular phenotype expression by controlling BRG1 in mesenchymal cells. Here, we report that SMANTIS is particularly highly expressed in monocytes and lost during differentiation into macrophages. Moreover, different types of myeloid leukemia presented specific SMANTIS expression patterns. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element on the RUNT domain. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding and altered the interaction of RUNX1 with EP300 and CBFB. Collectively, SMANTIS interacts with RUNX1 and attenuates monocyte adhesion, which might limit monocyte vascular egress.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Monócitos , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Monócitos/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Adesão Celular/genética , Diferenciação Celular
4.
Front Immunol ; 15: 1441637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229275

RESUMO

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.


Assuntos
Plaquetas , Leucócitos , Ativação Plaquetária , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Leucócitos/imunologia , Leucócitos/metabolismo , Plaquetas/metabolismo , Plaquetas/imunologia , Idoso , Adesão Celular , Fumar/efeitos adversos , Biomarcadores/sangue
5.
PLoS Biol ; 22(9): e3002757, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39231388

RESUMO

Integrins are fundamental for cell adhesion and the formation of focal adhesions (FA). Accordingly, these receptors guide embryonic development, tissue maintenance, and haemostasis but are also involved in cancer invasion and metastasis. A detailed understanding of the molecular interactions that drive integrin activation, FA assembly, and downstream signalling cascades is critical. Here, we reveal a direct association of paxillin, a marker protein of FA sites, with the cytoplasmic tails of the integrin ß1 and ß3 subunits. The binding interface resides in paxillin's LIM3 domain, where based on the NMR structure and functional analyses, a flexible, 7-amino acid loop engages the unstructured part of the integrin cytoplasmic tail. Genetic manipulation of the involved residues in either paxillin or integrin ß3 compromises cell adhesion and motility of murine fibroblasts. This direct interaction between paxillin and the integrin cytoplasmic domain identifies an alternative, kindlin-independent mode of integrin outside-in signalling particularly important for integrin ß3 function.


Assuntos
Paxilina , Ligação Proteica , Paxilina/metabolismo , Animais , Camundongos , Domínios Proteicos , Adesão Celular/fisiologia , Adesões Focais/metabolismo , Humanos , Movimento Celular , Integrina beta3/metabolismo , Integrina beta3/genética , Integrina beta3/química , Fibroblastos/metabolismo , Cadeias beta de Integrinas/metabolismo , Cadeias beta de Integrinas/química , Cadeias beta de Integrinas/genética , Integrina beta1/metabolismo , Transdução de Sinais
6.
Int J Biol Sci ; 20(11): 4114-4127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247831

RESUMO

Osteosarcoma is the most prevalent form of primary malignant bone tumor, primarily affecting children and adolescents. The nerve growth factors (NGF) referred to as neurotrophins have been associated with cancer-induced bone pain; however, the role of NGF in osteosarcoma has yet to be elucidated. In osteosarcoma samples from the Genomic Data Commons data portal, we detected higher levels of NGF and M2 macrophage markers, but not M1 macrophage markers. In cellular experiments, NGF-stimulated osteosarcoma conditional medium was shown to facilitate macrophage polarization from the M0 to the M2 phenotype. NGF also enhanced VCAM-1-dependent monocyte adhesion within the osteosarcoma microenvironment by down-regulating miR-513c-5p levels through the FAK and c-Src cascades. In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.


Assuntos
Monócitos , Fator de Crescimento Neural , Osteossarcoma , Microambiente Tumoral , Molécula 1 de Adesão de Célula Vascular , Osteossarcoma/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Humanos , Fator de Crescimento Neural/metabolismo , Animais , Microambiente Tumoral/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Camundongos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Macrófagos/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Camundongos Nus
7.
Nat Commun ; 15(1): 8044, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39271654

RESUMO

Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.


Assuntos
Adesão Celular , Desmogleína 3 , Queratinócitos , Fatores de Transcrição Kruppel-Like , Pênfigo , Humanos , Pênfigo/metabolismo , Pênfigo/patologia , Pênfigo/imunologia , Desmogleína 3/metabolismo , Desmogleína 3/genética , Animais , Queratinócitos/metabolismo , Camundongos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Autoanticorpos/imunologia , Desmossomos/metabolismo , Modelos Animais de Doenças , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Masculino
8.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273210

RESUMO

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood-brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood-brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.


Assuntos
Antígenos CD , Barreira Hematoencefálica , Adesão Celular , Células Endoteliais , Linfócitos T , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/imunologia , Animais , Antígenos CD/metabolismo , Antígenos CD/genética , Células Endoteliais/metabolismo , Células Endoteliais/imunologia , Camundongos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Camundongos Endogâmicos C57BL , Humanos , Encéfalo/metabolismo , Encéfalo/imunologia
9.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39273404

RESUMO

Astrogliosis is a process by which astrocytes, when exposed to inflammation, exhibit hypertrophy, motility, and elevated expression of reactivity markers such as Glial Fibrillar Acidic Protein, Vimentin, and Connexin43. Since 1999, our laboratory in Chile has been studying molecular signaling pathways associated with "gliosis" and has reported that reactive astrocytes upregulate Syndecan 4 and αVß3 Integrin, which are receptors for the neuronal glycoprotein Thy-1. Thy-1 engagement stimulates adhesion and migration of reactive astrocytes and induces neurons to retract neurites, thus hindering neuronal network repair. Reportedly, we have used DITNC1 astrocytes and neuron-like CAD cells to study signaling mechanisms activated by the Syndecan 4-αVß3 Integrin/Thy-1 interaction. Importantly, the sole overexpression of ß3 Integrin in non-reactive astrocytes turns them into reactive cells. In vitro, extensive passaging is a simile for "aging", and aged fibroblasts have shown ß3 Integrin upregulation. However, it is not known if astrocytes upregulate ß3 Integrin after successive cell passages. Here, we hypothesized that astrocytes undergoing long-term passaging increase ß3 Integrin expression levels and behave as reactive astrocytes without needing pro-inflammatory stimuli. We used DITNC1 cells with different passage numbers to study reactivity markers using immunoblots, immunofluorescence, and astrocyte adhesion/migration assays. We also evaluated ß3 Integrin levels by immunoblot and flow cytometry, as well as the neurotoxic effects of reactive astrocytes. Serial cell passaging mimicked the effects of inflammatory stimuli, inducing astrocyte reactivity. Indeed, in response to Thy-1, ß3 Integrin levels, as well as cell adhesion and migration, gradually increased with multiple passages. Importantly, these long-lived astrocytes expressed and secreted factors that inhibited neurite outgrowth and caused neuronal death, just like reactive astrocytes in culture. Therefore, we describe two DITNC1 cell types: a non-reactive type that can be activated with Tumor Necrosis Factor (TNF) and another one that exhibits reactive astrocyte features even in the absence of TNF treatment. Our results emphasize the importance of passage numbers in cell behavior. Likewise, we compare the pro-inflammatory stimulus versus long-term in-plate passaging of cell cultures and introduce them as astrocyte models to study the reactivity process.


Assuntos
Astrócitos , Adesão Celular , Movimento Celular , Gliose , Astrócitos/metabolismo , Gliose/metabolismo , Gliose/patologia , Animais , Antígenos Thy-1/metabolismo , Integrina alfaVbeta3/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Sindecana-4/metabolismo , Sindecana-4/genética , Camundongos , Linhagem Celular , Humanos , Células Cultivadas , Transdução de Sinais
10.
Colloids Surf B Biointerfaces ; 244: 114186, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39226849

RESUMO

Developing biomaterials with high osteogenic properties is crucial for achieving rapid bone repair and regeneration. This study focuses on the application of nanocrystal hydroxyapatite (nHAp) as a drug carrier to load Fu Yuan Huo Xue Decoction (FYHXD), a traditional Chinese medicine derived from Angelica sinensis, aiming to achieve improved efficacy in treating bone diseases such as osteoporosis. Through a facile physical adsorption approach, the FTIR result emerges new characteristic absorption peaks in the range of 1200-950 cm-1, proving the successful absorption of FYHXD onto the nHAp with a loading efficiency of 39.76 %. The modified nHAp exhibits a similar shape to the bone-derived hydroxyapatite nanocrystals, and their diameter increases slightly after modification. The drug release assay implies the rapid release of FYHXD in the first 10 h, followed by a continuously slow release within 70 h. The developed nHAp effectively enhances the adhesion, spreading, and proliferation of MC3T3-E1 cells in vitro, and significantly promotes their osteogenic differentiation, as indicated by increased alkaline phosphatase activity. Overall, the biocomposites hold great promise as active ingredients for integration into bone-associated biomaterials, offering the potential to stimulate spontaneous osteogenesis without requiring exogenous osteogenic factors.


Assuntos
Diferenciação Celular , Medicamentos de Ervas Chinesas , Durapatita , Nanopartículas , Osteogênese , Durapatita/química , Osteogênese/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Camundongos , Animais , Nanopartículas/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicina Tradicional Chinesa , Liberação Controlada de Fármacos , Fosfatase Alcalina/metabolismo , Tamanho da Partícula , Linhagem Celular , Adesão Celular/efeitos dos fármacos , Portadores de Fármacos/química
11.
PLoS Biol ; 22(9): e3002783, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39226305

RESUMO

Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye. The ommatidium is shaped as a hexagonal prism, and generating this 3D structure requires ommatidial cells to adopt specific apical and basal polygonal geometries. Using this model system, we find that generating cell type-specific basal geometries starts with patterning of the basal extracellular matrix, whereby Laminin accumulates at discrete locations across the basal surface of the retina. We find the Dystroglycan receptor complex (DGC) is required for this patterning by promoting localized Laminin accumulation at the basal surface of cells. Moreover, our results reveal that localized accumulation of Laminin and the DGC are required for directing Integrin adhesion. This induces cell basal geometry remodeling by anchoring the basal surface of cells to the extracellular matrix at specific, Laminin-rich locations. We propose that patterning of a basal extracellular matrix by generating discrete Laminin domains can direct Integrin adhesion to induce cell shape remodeling in epithelial morphogenesis.


Assuntos
Forma Celular , Proteínas de Drosophila , Drosophila melanogaster , Distroglicanas , Matriz Extracelular , Integrinas , Laminina , Retina , Animais , Distroglicanas/metabolismo , Laminina/metabolismo , Integrinas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Matriz Extracelular/metabolismo , Retina/metabolismo , Retina/crescimento & desenvolvimento , Retina/citologia , Retina/embriologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Morfogênese , Adesão Celular , Drosophila/metabolismo , Drosophila/crescimento & desenvolvimento
12.
J Appl Oral Sci ; 32: e20240154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258716

RESUMO

OBJECTIVE: Adhesion to dentin is a first step for a successful microbial root canal colonization. Cell hydrophobicity seems to have some influence in the Candida species adhesion to surfaces. To measure cell surface hydrophobicity and to investigate the adherence ability to human dentin among Candida albicans strains isolated from root canal and lingual dorsum via an in vitro study. METHODOLOGY: adhesion was quantified in function of dentin area covered by blastospores and/or hyphae presence detected by epifluorescence microscope. Cell surface hydrophobicity was estimated by assessing the percentage migration of cells from an aqueous phase to a hydrocarbon phase. Contact angles were measured by the sessile drop technique on the dentin surface using a contact angle measurements apparatus. We also examined the correlation between adhesion ability and hydrophobicity. RESULTS: although there was some intra-species variation in cell surface hydrophobicity, most isolates were characterized by moderate hydrophobicity. There was no significant difference in this parameter when the isolation niche was considered. Both root canal and lingual dorsum yeasts were able to adhere to dentin. No association was found between the strains' site of isolation and adhesion. Moreover, cell surface hydrophobicity and adhesion ability were not correlated. CONCLUSION: although hydrophobicity can influence Candida albicans virulence in many ways, this study suggests that this parameter by itself was not a good predictor of adhesion to dentin.


Assuntos
Candida albicans , Adesão Celular , Dentina , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície , Candida albicans/fisiologia , Humanos , Dentina/microbiologia , Adesão Celular/fisiologia , Cavidade Pulpar/microbiologia , Microscopia de Fluorescência
13.
Sci Rep ; 14(1): 21097, 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256445

RESUMO

Polymer composite scaffolds hold promise in bone tissue engineering due to their biocompatibility, mechanical properties, and reproducibility. Among these materials, polylactic acid (PLA), a biodegradable plastics has gained attention for its processability characteristics. However, a deeper understanding of how PLA scaffold surface properties influence cell behavior is enssential for advancing its applications. In this study, 3D-printed PLA scaffolds containing hydroxyapatite (HA) were analyzed using atomic force microscopy and nanomechanical mapping. The addition of HA significantly increased key surface properties compared to unmodified PLA scaffols. Notably, the HA-modified scaffold demonstrated Gaussian distribution of stiffness and adhesive forces, in contrast to the bimodal properties observed in the unmodified PLA scaffolds. Human adipose-derived mesenchymal stem cell (hADMSC) seeded on the 3D-printed PLA scaffolds blended with 10% HA (P10) exhibited strong attachment. After four weeks, osteogenic differentiation of hADMSCs was detected, with calcium deposition reaching 6.76% ± 0.12. These results suggest that specific ranges of stiffness and adhesive forces of the composite scaffold can support cell attachement, and mineralization. The study highlights that tailoring suface properties of composite scaffolds is crucial for modulating cellular interactions, thus advancing the development of effective bone replacement materials.


Assuntos
Diferenciação Celular , Durapatita , Células-Tronco Mesenquimais , Osteogênese , Poliésteres , Propriedades de Superfície , Engenharia Tecidual , Alicerces Teciduais , Durapatita/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Alicerces Teciduais/química , Poliésteres/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual/métodos , Impressão Tridimensional , Microscopia de Força Atômica , Células Cultivadas , Adesão Celular , Materiais Biocompatíveis/química
14.
ACS Appl Mater Interfaces ; 16(36): 47178-47191, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39222394

RESUMO

Guided bone regeneration (GBR) technology has been demonstrated to be an effective method for reconstructing bone defects. A membrane is used to cover the bone defect to stop soft tissue from growing into it. The biosurface design of the barrier membrane is key to the technology. In this work, an asymmetric functional gradient Janus membrane was designed to address the bidirectional environment of the bone and soft tissue during bone reconstruction. The Janus membrane was simply and efficiently prepared by the multilayer self-assembly technique, and it was divided into the polycaprolactone isolation layer (PCL layer, GBR-A) and the nanohydroxyapatite/polycaprolactone/polyethylene glycol osteogenic layer (HAn/PCL/PEG layer, GBR-B). The morphology, composition, roughness, hydrophilicity, biocompatibility, cell attachment, and osteogenic mineralization ability of the double surfaces of the Janus membrane were systematically evaluated. The GBR-A layer was smooth, dense, and hydrophobic, which could inhibit cell adhesion and resist soft tissue invasion. The GBR-B layer was rough, porous, hydrophilic, and bioactive, promoting cell adhesion, proliferation, matrix mineralization, and expression of alkaline phosphatase and RUNX2. In vitro and in vivo results showed that the membrane could bind tightly to bone, maintain long-term space stability, and significantly promote new bone formation. Moreover, the membrane could fix the bone filling material in the defect for a better healing effect. This work presents a straightforward and viable methodology for the fabrication of GBR membranes with Janus-based bioactive surfaces. This work may provide insights for the design of biomaterial surfaces and treatment of bone defects.


Assuntos
Regeneração Óssea , Osteogênese , Poliésteres , Regeneração Óssea/efeitos dos fármacos , Animais , Poliésteres/química , Poliésteres/farmacologia , Osteogênese/efeitos dos fármacos , Durapatita/química , Durapatita/farmacologia , Polietilenoglicóis/química , Membranas Artificiais , Adesão Celular/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Regeneração Tecidual Guiada/métodos , Coelhos , Camundongos
15.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273096

RESUMO

In recent years, with the advent of a super-aged society, lifelong dental care has gained increasing emphasis, and implant therapy for patients with an edentulous jaw has become a significant option. However, for implant therapy to be suitable for elderly patients with reduced regenerative and immunological capabilities, higher osteoconductive and antimicrobial properties are required on the implant surfaces. Silicon nitride, a non-oxide ceramic known for its excellent mechanical properties and biocompatibility, has demonstrated high potential for inducing hard tissue differentiation and exhibiting antibacterial properties. In this study, silicon nitride was deposited on pure titanium metal surfaces and evaluated for its biocompatibility and antibacterial properties. The findings indicate that silicon nitride improves the hydrophilicity of the material surface, enhancing the initial adhesion of rat bone marrow cells and promoting hard tissue differentiation. Additionally, the antibacterial properties were assessed using Staphylococcus aureus, revealing that the silicon nitride-coated surfaces exhibited significant antibacterial activity. Importantly, no cytotoxicity was observed, suggesting that silicon nitride-coated titanium could serve as a novel implant material.


Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Compostos de Silício , Staphylococcus aureus , Propriedades de Superfície , Titânio , Titânio/química , Titânio/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Ratos , Staphylococcus aureus/efeitos dos fármacos , Compostos de Silício/química , Compostos de Silício/farmacologia , Teste de Materiais , Adesão Celular/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos
16.
J Cell Sci ; 137(20)2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39129707

RESUMO

Trichomonas vaginalis causes trichomoniasis, the most common non-viral sexually transmitted disease worldwide. As an extracellular parasite, adhesion to host cells is essential for the development of infection. During attachment, the parasite changes its tear ovoid shape to a flat ameboid form, expanding the contact surface and migrating through tissues. Here, we have identified a novel structure formed at the posterior pole of adherent parasite strains, resembling the previously described uropod, which appears to play a pivotal role as an anchor during the attachment process. Moreover, our research demonstrates that the overexpression of the tetraspanin T. vaginalis TSP5 protein (TvTSP5), which is localized on the cell surface of the parasite, notably enhances the formation of this posterior anchor structure in adherent strains. Finally, we demonstrate that parasites that overexpress TvTSP5 possess an increased ability to adhere to host cells, enhanced aggregation and reduced migration on agar plates. Overall, these findings unveil novel proteins and structures involved in the intricate mechanisms of T. vaginalis interactions with host cells.


Assuntos
Proteínas de Protozoários , Trichomonas vaginalis , Trichomonas vaginalis/genética , Humanos , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Adesão Celular , Tetraspaninas/metabolismo , Tetraspaninas/genética , Membrana Celular/metabolismo , Interações Hospedeiro-Parasita , Extensões da Superfície Celular/metabolismo , Animais
17.
J Cell Sci ; 137(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39143856

RESUMO

Fluid shear stress (FSS) from blood flow, sensed by the vascular endothelial cells (ECs) that line all blood vessels, regulates vascular development during embryogenesis, controls adult vascular physiology and determines the location of atherosclerotic plaque formation. Although a number of papers have reported a crucial role for cell-cell adhesions or adhesion receptors in these processes, a recent publication has challenged this paradigm, presenting evidence that ECs can very rapidly align in fluid flow as single cells without cell-cell contacts. To address this controversy, four independent laboratories assessed EC alignment in fluid flow across a range of EC cell types. These studies demonstrate a strict requirement for cell-cell contact in shear stress sensing over timescales consistent with previous literature and inconsistent with the newly published data.


Assuntos
Células Endoteliais , Junções Intercelulares , Mecanotransdução Celular , Estresse Mecânico , Humanos , Junções Intercelulares/metabolismo , Células Endoteliais/metabolismo , Animais , Resistência ao Cisalhamento , Adesão Celular/fisiologia
18.
ACS Nano ; 18(36): 24953-24967, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39197151

RESUMO

Strengthening tumor cellular adhesion through regulating the concentration of extracellular Ca2+ is highly challenging and promising for antimetastasis. Herein, a pH-responsive conjugated polymer-calcium composite nanoparticle (PFV/CaCO3/PDA@PEG) is developed for calcium-mediated cell adhesion enhancement-based antimetastasis and reactive oxygen species (ROS)-triggered calcium overload and photodynamic therapy (PDT) synergistic tumor treatment. PFV/CaCO3/PDA@PEG is mainly equipped with conjugated poly(fluorene-co-vinylene) (PFV-COOH)-composited CaCO3 nanoparticles, which can be rapidly decomposed under the tumor acidic microenvironment, effectively releasing Ca2+ and the photosensitizer PFV-COOH. The high extracellular Ca2+ concentration facilitates the generation of dimers between two adjacent cadherin ectodomains, which greatly enhances cell-cell adhesion and suppresses tumor metastasis. The inhibition rates are 97 and 87% for highly metastatic tumor cells 4T1 and MCF-7, respectively. Such a well-designed nanoparticle also contributes to realizing PDT, mitochondrial dysfunction, and ROS-triggered Ca2+ overload synergistic therapy. Furthermore, PFV/CaCO3/PDA@PEG displayed superior in vivo inhibition of 4T1 tumor growth and demonstrated a marked antimetastatic effect by both intravenous and intratumoral injection modes. Thus, this study provides a powerful strategy for calcium-mediated metastasis inhibition for tumor therapy.


Assuntos
Antineoplásicos , Cálcio , Adesão Celular , Nanopartículas , Fotoquimioterapia , Espécies Reativas de Oxigênio , Nanopartículas/química , Humanos , Animais , Cálcio/metabolismo , Adesão Celular/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Polímeros/química , Polímeros/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Feminino , Camundongos Endogâmicos BALB C , Células MCF-7 , Carbonato de Cálcio/química , Carbonato de Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Metástase Neoplásica , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais
19.
Sci Rep ; 14(1): 20175, 2024 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215026

RESUMO

Talin2 is localized to large focal adhesions and is indispensable for traction force generation, invadopodium formation, cell invasion as well as metastasis. Talin2 has a higher affinity toward ß-integrin tails than talin1. Moreover, disruption of the talin2-ß-integrin interaction inhibits traction force generation, invadopodium formation and cell invasion, indicating that a strong talin2-ß-integrin interaction is required for talin2 to fulfill these functions. Nevertheless, the role of talin2 in mediation of these processes remains unknown. Here we show that talin2 binds to the N-terminus of non-muscle myosin IIA (NMIIA) through its F3 subdomain. Moreover, talin2 co-localizes with NMIIA at cell edges as well as at some cytoplasmic spots. Talin2 also co-localizes with cortactin, an invadopodium marker. Furthermore, overexpression of NMIIA promoted the talin2 head binding to the ß1-integrin tail, whereas knockdown of NMIIA reduced fibronectin and matrix metalloproteinase secretion as well as inhibited cell attachment on fibronectin-coated substrates. These results suggest that talin2 binds to NMIIA to control the secretion of extracellular matrix proteins and this interaction modulates cell adhesion.


Assuntos
Adesão Celular , Fibronectinas , Miosina não Muscular Tipo IIA , Ligação Proteica , Talina , Animais , Humanos , Cortactina/metabolismo , Fibronectinas/metabolismo , Adesões Focais/metabolismo , Integrina beta1/metabolismo , Miosina não Muscular Tipo IIA/metabolismo , Podossomos/metabolismo , Talina/metabolismo , Camundongos
20.
Front Cell Infect Microbiol ; 14: 1404120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211799

RESUMO

Background: Toxoplasma gondii (T. gondii) is a widespread, zoonotic protozoan intracellular parasite with a complex life cycle, which can cause toxoplasmosis, a potentially serious disease. During the invasion process, T. gondii proteins first bind to the relevant host cell receptors, such as glycosaminoglycan molecule (GAG-binding motif), which is one of the main receptors for parasites or virus to infect host cells. However, research on TGME49_216510 (T. gondii Trx21), a protein from Toxoplasma gondii, is limited. Methods: Bioinformatics analysis of the Trx21 protein was performed firstly. And specific primers were then designed using the conserved domain and GAG-binding motif to amplify, express, and purify a fragment of the Trx21 protein. The purified Trx21-GST protein was used for antioxidant and cell adhesion experiments. Simultaneously, mice were immunized with Trx21-His to generate specific polyclonal antibodies for subcellular localization analysis. Results: The Trx21 protein, consisting of 774 amino acids, included a transmembrane region, three GAG-binding motifs, and a Thioredoxin-like domain. The recombinant Trx21-His protein had a molecular mass of about 31 kDa, while the Trx21-GST protein had a molecular mass of about 55 kDa, which was analyzed by SDS-PAGE and Western blot. Subcellular localization analysis by IFA revealed that Trx21 is predominantly distributed in the cytoplasm of T. gondii. Furthermore, Trx21 exhibited a protective effect on supercoiled DNA against metal-catalyzed oxidation (MCO) and demonstrated adhesion abilities to Vero cells. Conclusions: These results indicate that Trx21 plays an important role in host cell interaction and oxidative damage.


Assuntos
Adesão Celular , Proteínas de Protozoários , Tiorredoxinas , Toxoplasma , Toxoplasma/metabolismo , Toxoplasma/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Animais , Camundongos , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Antioxidantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/isolamento & purificação , Biologia Computacional , Células Vero , Chlorocebus aethiops , Toxoplasmose/parasitologia , Humanos
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