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1.
Proc Natl Acad Sci U S A ; 121(15): e2321759121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38579009

RESUMEN

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to qua1 and qua2 mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Adhesión Celular/genética , Pectinas/metabolismo , Aparato de Golgi/genética , Aparato de Golgi/metabolismo , Pared Celular/metabolismo
2.
Anticancer Agents Med Chem ; 24(13): 982-989, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38629374

RESUMEN

BACKGROUND: Monochasma savatieri, is a rare and endangered plant used to treat cancer in Chinese traditional medicine. OBJECTIVE: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory, and anti-adhesion effects on breast cancer cells. METHODS: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet (CV) staining, wound-healing, and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Immunofluorescent assays confirmed caveolin-1 expression in MDA-MB-231 cells. RESULTS: Survival and cell cycle of MCF7 and MDA-MB-231 cells were not modified by doses up to 500 µg/mL of the extract. The extract inhibited cell migration and adhesion of MDA-MB-231 cells. When cells were exposed to the extract, there was a slight decrease in protein expression of factors related to epithelial-to-mesenchymal transition (snail and vimentin) and a strong decrease in the expression of the oncogenic membrane protein caveolin- 1. Furthermore, the levels of phosphorylated Erk and Akt were also decreased. The content of acteoside, a phenylpropanoid glycoside with reported anti-cancer activity present in M. savatieri, was almost 5 times as much as isoacteoside. CONCLUSION: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exhibited anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects.


Asunto(s)
Neoplasias de la Mama , Adhesión Celular , Movimiento Celular , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Extractos Vegetales , Humanos , Movimiento Celular/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Adhesión Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Femenino , Relación Estructura-Actividad , Estructura Molecular , Células Tumorales Cultivadas , Agua/química , Línea Celular Tumoral
3.
Phytomedicine ; 128: 155403, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38564920

RESUMEN

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.


Asunto(s)
Inflamación , Músculo Liso Vascular , Sesquiterpenos , Animales , Masculino , Ratones , Antiinflamatorios/farmacología , Adhesión Celular/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Proteína 1 Asociada A ECH Tipo Kelch/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metilaminas/farmacología , Ratones Endogámicos C57BL , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Sesquiterpenos/farmacología , Transducción de Señal/efectos de los fármacos , Gutatión-S-Transferasa pi/efectos de los fármacos , Gutatión-S-Transferasa pi/metabolismo
4.
J Med Food ; 27(5): 419-427, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38656897

RESUMEN

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.


Asunto(s)
Actinidia , Adhesión Celular , Glucógeno Sintasa Quinasa 3 beta , Células Endoteliales de la Vena Umbilical Humana , Inositol , Monocitos , FN-kappa B , Fosfohidrolasa PTEN , Extractos Vegetales , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factor de Necrosis Tumoral alfa , Molécula 1 de Adhesión Celular Vascular , Molécula 1 de Adhesión Celular Vascular/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Humanos , FN-kappa B/metabolismo , FN-kappa B/genética , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Actinidia/química , Animales , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Adhesión Celular/efectos de los fármacos , Ratones , Inositol/farmacología , Inositol/análogos & derivados , Ratones Endogámicos C57BL , Aterosclerosis/metabolismo , Aterosclerosis/tratamiento farmacológico , Masculino
5.
Nat Rev Nephrol ; 20(6): 371-385, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38443711

RESUMEN

Podocytes form the backbone of the glomerular filtration barrier and are exposed to various mechanical forces throughout the lifetime of an individual. The highly dynamic biomechanical environment of the glomerular capillaries greatly influences the cell biology of podocytes and their pathophysiology. Throughout the past two decades, a holistic picture of podocyte cell biology has emerged, highlighting mechanobiological signalling pathways, cytoskeletal dynamics and cellular adhesion as key determinants of biomechanical resilience in podocytes. This biomechanical resilience is essential for the physiological function of podocytes, including the formation and maintenance of the glomerular filtration barrier. Podocytes integrate diverse biomechanical stimuli from their environment and adapt their biophysical properties accordingly. However, perturbations in biomechanical cues or the underlying podocyte mechanobiology can lead to glomerular dysfunction with severe clinical consequences, including proteinuria and glomerulosclerosis. As our mechanistic understanding of podocyte mechanobiology and its role in the pathogenesis of glomerular disease increases, new targets for podocyte-specific therapeutics will emerge. Treating glomerular diseases by targeting podocyte mechanobiology might improve therapeutic precision and efficacy, with potential to reduce the burden of chronic kidney disease on individuals and health-care systems alike.


Asunto(s)
Podocitos , Podocitos/fisiología , Humanos , Fenómenos Biomecánicos , Mecanotransducción Celular/fisiología , Citoesqueleto/fisiología , Biofisica , Animales , Adhesión Celular/fisiología
6.
Nat Rev Mol Cell Biol ; 25(4): 252-269, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38093099

RESUMEN

Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms. Adherens junctions are key subcellular structures, built from clusters of classical cadherin receptors. They mediate physical interactions between cells and connect biochemical signalling to the physical characteristics of cell contacts, hence playing a fundamental role in tissue morphogenesis. In this Review, we take advantage of the results of recent, quantitative measurements of tissue mechanics to relate the molecular and cellular characteristics of adherens junctions, including adhesion strength, tension and dynamics, to the emergent physical state of embryonic tissues. We focus on systems in which cell-cell interactions are the primary contributor to morphogenesis, without significant contribution from cell-matrix interactions. We suggest that emergent tissue mechanics is an important direction for future research, bridging cell biology, developmental biology and mechanobiology to provide a holistic understanding of morphogenesis in health and disease.


Asunto(s)
Uniones Adherentes , Cadherinas , Uniones Adherentes/metabolismo , Cadherinas/metabolismo , Comunicación Celular , Morfogénesis , Desarrollo Embrionario , Adhesión Celular/fisiología
7.
PLoS One ; 18(11): e0293961, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37939087

RESUMEN

Pectin and its modification influence the plasticity and strength of the plant cell wall controlling cell adhesion, size, shape, and pathogen resistance. The Golgi membrane anchored QUA1, QUA2, and GAUT9 Golgi enzymes synthesize and esterify pectin, which is then secreted and selectively de-esterified to potentiate structure influencing crosslinks in the cell wall. Mutations in members of the family of non-enzymatic ELMO Golgi membrane proteins lead to a reduction of pectin levels, cell adhesion, and hypocotyl tensile strength. Results from immunoprecipitation of Golgi protein complexes reveal that ELMO1-GFP is associated with pectin biosynthesis and modifying enzymes QUA1, QUA2, and GAUT9. In a yeast two and three hybrid assay, ELMO1 can bind directly to QUA1, GAUT9 or ELMO4, but QUA1, QUA2 or GAUT9 do not bind to each other. A yeast 3 hybrid assay provides evidence that ELMO1 can mediate the binding of QUA1 and QUA2. Taken together, these results indicate that the 20 kDa ELMO1 serves to facilitate some aspect of pectin synthesis and modification that leads to sufficient accumulation to allow cell adhesion, and we speculate that ELMOs help to scaffold key enzymes in this process.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Pectinas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Saccharomyces cerevisiae/metabolismo , Adhesión Celular , Pared Celular/metabolismo
8.
Sci Rep ; 13(1): 18365, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884622

RESUMEN

The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue interface plays a major role in enhancing the interactions between a biomaterial and living cells. Bio-integration is particularly important in case of various electrotherapies, since a close contact between tissue and electrode's surface facilitates treatment. A promising approach towards surface biofunctionalization involves the electrografting of diazonium salts followed by the modification of organic layer with pro-adhesive polypeptides. This study focuses on the modification of platinum electrodes with a 4-nitrobenzenediazonium layer, which is then converted to the aminobenzene moiety. The electrodes are further biofunctionalized with polypeptides (polylysine and polylysine/laminin) to enhance cell adhesion. This study also explores the differences between physical and chemical coupling of selected polypeptides to modulate pro-adhesive nature of Pt electrodes with respect to human neuroblastoma SH-SY5Y cells and U87 astrocytes. Our results demonstrate the significant enhancement in cell adhesion for biofunctionalized electrodes, with more amplified adhesion noted for covalently coupled polypeptides. The implications of this research are crucial for the development of more effective and functional biomaterials, particularly biomedical electrodes, which have the potential to advance the field of bioelectronics and improve patients' outcomes.


Asunto(s)
Neuroblastoma , Polilisina , Humanos , Adhesivos , Materiales Biocompatibles , Péptidos , Adhesión Celular , Propiedades de Superficie
9.
Proc Natl Acad Sci U S A ; 120(31): e2301881120, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37494400

RESUMEN

Integrin adhesion complexes are essential membrane-associated cellular compartments for metazoan life. The formation of initial integrin adhesion complexes is a dynamic process involving focal adhesion proteins assembled at the integrin cytoplasmic tails and the inner leaflet of the plasma membrane. The weak multivalent protein interactions within the complex and with the plasma membrane suggest that liquid-liquid phase separation could play a role in the nascent adhesion assembly. Here, we report that solid-supported lipid membranes supplemented with phosphoinositides induce the phase separation of minimal integrin adhesion condensates composed of integrin ß1 tails, kindlin, talin, paxillin, and FAK at physiological ionic strengths and protein concentrations. We show that the presence of phosphoinositides is key to enriching kindlin and talin on the lipid membrane, which is necessary to further induce the phase separation of paxillin and FAK at the membrane. Our data demonstrate that lipid membrane surfaces set the local solvent conditions for steering the membrane-localized phase separation even in a regime where no condensate formation of proteins occurs in bulk solution.


Asunto(s)
Integrinas , Talina , Animales , Integrinas/metabolismo , Paxillin/metabolismo , Talina/metabolismo , Membrana Celular/metabolismo , Integrina beta1/metabolismo , Fosfatidilinositoles , Adhesión Celular/fisiología
10.
J Ethnopharmacol ; 315: 116644, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37196814

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zhuidu Formula (ZDF) is composed of triptolide, cinobufagin and paclitaxel, which are the active ingredients of Tripterygium wilfordii Hook. F, dried toad skin and Taxus wallichiana var. chinensis (Pilg) Florin, respectively. Modern pharmacological studies show that triptolide, cinobufagin, and paclitaxel are well-known natural compounds that exert anti-tumor effects by interfering with DNA synthesis, inducing tumor cell apoptosis, and inhibiting the dynamic balance of the tubulin. However, the mechanism by which the three compounds inhibit triple-negative breast cancer (TNBC) metastasis is unknown. OBJECTIVE: The objective of this investigation was to examine the inhibitory essences of ZDF on the metastasis of TNBC and elucidate its potential mechanism. MATERIALS AND METHODS: Cell viability of triptolide (TPL), cinobufagin (CBF), and paclitaxel (PTX) on MDA-MB-231 cells was assessed employing a CCK-8 assay. The drug interactions of the three drugs on MDA-MB-231 cells were determined in vitro utilizing the Chou-Talalay method. MDA-MB-231 cells were identified for migration, invasion and adhesion in vitro through the implementation of the scratch assay, transwell assay and adhesion assay, respectively. The formation of cytoskeleton protein F-actin was detected by immunofluorescence assay. The expressions of MMP-2 and MMP-9 in the supernatant of the cells were determined by ELISA analysis. The Western blot and RT-qPCR were employed to explore the protein expressions associated with the dual signaling pathways of RhoA/ROCK and CDC42/MRCK. The anti-tumor efficacy of ZDF in vivo and its preliminary mechanism were investigated in the mouse 4T1 TNBC model. RESULTS: The results demonstrated that ZDF could significantly reduce the viability of the MDA-MB-231 cell, and the combination index (CI) values of actual compatibility experimental points were all less than 1, demonstrating a favorable synergistic compatibility relationship. It was found that ZDF reduces RhoA/ROCK and CDC42/MRCK dual signaling pathways, which are responsible for MDA-MB-231cell migration, invasion, and adhesion. Additionally, there has been a significant reduction in the manifestation of cytoskeleton-related proteins. Furthermore, the expression levels of RhoA, CDC42, ROCK2, and MRCKß mRNA and protein were down-regulated. ZDF significantly decreased the protein expressions of vimentin, cytokeratin-8, Arp2 and N-WASP, and inhibited actin polymerization and actomyosin contraction. Furthermore, MMP-2 and MMP-9 levels in the high-dose ZDF group were decreased by 30% and 26%, respectively. ZDF significantly reduced the tumor volume and protein expressions of ROCK2 and MRCKß in tumor tissues without eliciting any perceptible alterations in the physical mass of the mice, and the reduction was more pronounced than that of the BDP5290 treated group. CONCLUSION: The current investigation demonstrates that ZDF exhibits a proficient inhibitory impact on TNBC metastasis by regulating cytoskeletal proteins through the dual signaling pathways of RhoA/ROCK and CDC42/MRCK. Furthermore, the findings indicate that ZDF has significant anti-tumorigenic and anti-metastatic characteristics in breast cancer animal models.


Asunto(s)
Medicina Tradicional China , Proteína Quinasa de Distrofia Miotónica , Invasividad Neoplásica , Paclitaxel , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Quinasas Asociadas a rho , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Proteína Quinasa de Distrofia Miotónica/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Citoesqueleto/efectos de los fármacos , Etnofarmacología , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Células MDA-MB-231 , Adhesión Celular/efectos de los fármacos , Humanos , Animales , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Sinergismo Farmacológico , Metaloproteinasas de la Matriz/metabolismo , Actinas/metabolismo , Procesos de Crecimiento Celular/efectos de los fármacos
11.
Braz Dent J ; 34(2): 97-104, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37194860

RESUMEN

The increase in life expectancy has led to a higher incidence of osteoporosis, characterized by an imbalance in bone remodeling. Several drugs are used for its treatment, but most promote undesirable side effects. The present investigation evaluated the effects of two low concentrations of grape seed extract (GSE) rich in proanthocyanidins on MC3T3-E1 osteoblastic cells. The cells were cultured in an osteogenic medium and divided into control (C), 0.1 µg/mL GSE (GSE0.1), and 1.0 µg/mL GSE (GSE1.0) groups to evaluate cell morphology, adhesion, and proliferation, in situ alkaline phosphatase (ALP) detection, mineralization and immunolocalization of osteopontin (OPN). The data obtained were analyzed by statistical tests for a significance of 5%. Cell morphology was maintained with both GSE concentrations, whereas cell adhesion significantly increased within three days in all groups. Cell proliferation increased significantly at seven days of culture, followed by a significant decrease in all experimental periods, with no statistical difference among them. In situ detection of ALP and mineralization increased with time, but within each period, no statistical differences among groups were observed. The expression of osteopontin was distributed regularly with more intensity after 24 hours in the GSE0.1 group. After three days, OPN expression was more intense in the control group, followed by GSE0.1 and GSE1.0 groups. Data obtained suggest that low concentrations of GSE do not affect the morphology and may stimulate the functional activity of osteoblastic cells.


Asunto(s)
Extracto de Semillas de Uva , Extracto de Semillas de Uva/farmacología , Osteopontina/metabolismo , Adhesión Celular , Osteogénesis , Proliferación Celular , Osteoblastos , Diferenciación Celular , Fosfatasa Alcalina/metabolismo
12.
Nutrients ; 15(7)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37049512

RESUMEN

Sea urchins have emerged as an important source of bioactive compounds with anti-inflammatory and antioxidant properties relevant to human health. Since inflammation is a crucial pathogenic process in the development and progression of atherosclerosis, we here assessed the potential anti-inflammatory and vasculoprotective effects of coelomic red-cell methanolic extract of the black sea urchin Arbacia lixula in an in vitro model of endothelial cell dysfunction. Human microvascular endothelial cells (HMEC-1) were pretreated with A. lixula red-cell extract (10 and 100 µg/mL) before exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The extract was non-toxic after 24 h cell treatment and was characterized by antioxidant power and phenol content. The TNF-α-stimulated expression of adhesion molecules (VCAM-1, ICAM-1) and cytokines/chemokines (MCP-1, CCL-5, IL-6, IL-8, M-CSF) was significantly attenuated by A. lixula red-cell extract. This was functionally accompanied by a reduction in monocyte adhesion and chemotaxis towards activated endothelial cells. At the molecular level, the tested extract significantly counteracted the TNF-α-stimulated activation of the pro-inflammatory transcription factor NF-κB. These results provide evidence of potential anti-atherosclerotic properties of A. lixula red-cell extract, and open avenues in the discovery and development of dietary supplements and/or drugs for the prevention or treatment of cardiovascular diseases.


Asunto(s)
Arbacia , Animales , Humanos , Arbacia/metabolismo , Células Endoteliales/metabolismo , Extractos Celulares/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , FN-kappa B/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Citocinas/metabolismo , Erizos de Mar/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismo , Adhesión Celular
13.
Biomater Sci ; 11(11): 3893-3905, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37083965

RESUMEN

Integrin-mediated osteoblast adhesion to adsorbed extracellular ligands on orthopedic implants is crucial for the subsequent osteoblast behaviors and ultimate osseointegration. Considerable research efforts have focused on the development of implant surfaces that promote the adsorption of extracellular ligands, but ignored the fact that integrin binding to ligands requires divalent cations (such as Mn2+). Here, three kinds of Mn-doped nanowire-structured TiO2 coatings with 1.9, 3.9, and 8.8 wt% dopant contents (Mn1-, Mn2-, and Mn3-TiO2) were synthesized on Ti implants to enhance integrin-mediated osteoblastic responses. The Mg-doped and undoped TiO2 nanocoatings served as the control. Mn element was not only successfully incorporated into the TiO2 matrix, but also formed an oxygen-deficient Mn oxide on the nanowire surface. Although the adsorbed fibronectin (Fn) amount on Mn-doped nanocoatings and its unfolded status were slightly attenuated with increasing Mn amount, the interaction between the coating extract and Fn demonstrated a Mn2+-induced unfolding of Fn with the exposure of the RGD motif. Compared to the Mn1-, Mn2- and Mg-doped TiO2 nanocoatings, the Mn3-TiO2 nanocoating significantly upregulated the expression of integrin α5ß1 probably through increasing the ligand-binding affinity of the integrin rather than integrin binding sites in Fn. Consistent with the activation trend of integrin α5ß1, the Mn3-TiO2 nanocoating enhanced cell adhesion with the long stretched structure of actin fibers and extensive formation of vinculin focal adhesion spots and upregulated the levels of alkaline phosphatase and osteocalcin activities. Therefore, Mn supplementation of orthopedic implants may be a promising way to improve osteogenesis at the implant surface.


Asunto(s)
Integrina alfa5beta1 , Integrinas , Manganeso , Adhesión Celular , Titanio/farmacología , Titanio/química , Suplementos Dietéticos , Fibronectinas/metabolismo
14.
Adv Colloid Interface Sci ; 314: 102860, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36931199

RESUMEN

Polypyrrole (PPy) is one of the most studied conductive polymers due to its electrical conductivity and biological properties, which drive the possibility of numerous applications in the biomedical area. The physical-chemical features of PPy allow the manufacture of biocompatible devices, enhancing cell adhesion and proliferation. Furthermore, owing to the electrostatic interactions between the negatively charged bacterial cell wall and the positive charges in the polymer structure, PPy films can perform an effective antimicrobial activity. PPy is also frequently associated with biocompatible agents and antimicrobial compounds to improve the biological response. Thus, this comprehensive review appraised the available evidence regarding the PPy-based films deposited on metallic implanted devices for biomedical applications. We focus on understanding key concepts that could influence PPy attributes regarding antimicrobial effect and cell behavior under in vitro and in vivo settings. Furthermore, we unravel the several agents incorporated into the PPy film and strategies to improve its functionality. Our findings suggest that incorporating other elements into the PPy films, such as antimicrobial agents, biomolecules, and other biocompatible polymers, may improve the biological responses. Overall, the basic properties of PPy, when combined with other composites, electrostimulation techniques, or surface treatment methods, offer great potential in biocompatibility and/or antimicrobial activities. However, challenges in synthesis standardization and potential limitations such as low adhesion and mechanical strength of the film must be overcome to improve and broaden the application of PPy film in biomedical devices.


Asunto(s)
Polímeros , Pirroles , Polímeros/farmacología , Polímeros/química , Pirroles/farmacología , Pirroles/química , Adhesión Celular , Conductividad Eléctrica
15.
Mar Drugs ; 21(2)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36827101

RESUMEN

Collagen is the most ubiquitous biomacromolecule found in the animal kingdom and is commonly used as a biomaterial in regenerative medicine therapies and biomedical research. The collagens used in these applications are typically derived from mammalian sources which poses sociological issues due to widespread religious constraints, rising ethical concern over animal rights and the continuous risk of zoonotic disease transmission. These issues have led to increasing research into alternative collagen sources, of which marine collagens, in particular from jellyfish, have emerged as a promising resource. This study provides a characterization of the biophysical properties and cell adhesion interactions of collagen derived from the jellyfish Rhizostoma pulmo (JCol). Circular dichroism spectroscopy and atomic force microscopy were used to observe the triple-helical conformation and fibrillar morphology of JCol. Heparin-affinity chromatography was also used to demonstrate the ability of JCol to bind to immobilized heparin. Cell adhesion assays using integrin blocking antibodies and HT-1080 human fibrosarcoma cells revealed that adhesion to JCol is primarily performed via ß1 integrins, with the exception of α2ß1 integrin. It was also shown that heparan sulfate binding plays a much greater role in fibroblast and mesenchymal stromal cell adhesion to JCol than for type I mammalian collagen (rat tail collagen). Overall, this study highlights the similarities and differences between collagens from mammalian and jellyfish origins, which should be considered when utilizing alternative collagen sources for biomedical research.


Asunto(s)
Cnidarios , Colágeno , Escifozoos , Animales , Humanos , Ratas , Adhesión Celular , Cnidarios/metabolismo , Colágeno/química , Integrinas/metabolismo , Escifozoos/química
16.
Food Chem ; 413: 135574, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36739644

RESUMEN

Cell adhesion of four cultivars of tomato fruit, "Micro Tom (MT)", "Heinz 1706 (H1706)", "Money Maker (MM)", "Ailsa Craig (AC)" were evaluated and cell walls were analyzed in order to assess the possible contribution of pectic and hemicellulosic polysaccharides to the softening and altered cell adhesion at two different stages of ripeness. Cell wall material (CWM) and solubilised fractions of green and red ripe fruit were analyzed by chemical, enzymatic techniques. In comparison with the four cultivars of tomato fruits, H1706 and MM are harder than MT and AC at both green and red ripe stage. The ripening-associated solubilisation of rhamnogalacturonan-riched pectic polysaccharides was reduced in H1706 and MM, and the content of side -chain sugars from RG-I reduced by more than 50% in MT and AC. In addition to recognized pectic modifying enzymes, RGase had a good effect on cell separation of H1706 and MM fruit at red ripe stage. The higher RG-I content and branching degree have been associated with increased cell adhesion and reduced cell wall porosity, thus maintained fruit firmness.


Asunto(s)
Pectinas , Solanum lycopersicum , Pectinas/metabolismo , Frutas/metabolismo , Adhesión Celular , Polisacáridos/análisis , Pared Celular/química
17.
J Colloid Interface Sci ; 635: 503-513, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36599247

RESUMEN

HYPOTHESIS: Selenium (Se)-containing compound is sensitive to redox stimulation, showing hydrophobic-hydrophilic reversible transition. Introduction of such compound into honeycomb film could confer on it redox-switchable surface wettability, which is expected to control cell adhesion/detachment behavior. EXPERIMENTS: Didodecyl selenide was designed and mixed with polystyrene to prepare honeycomb films using "breath figure" method. The film microstructures were characterized by scanning electron microscope and atomic force microscopy, and the arrangement of Se atoms in honeycomb film was determined by X-ray photoelectron spectroscopy and energy dispersive spectrometry. The variation of film wettability upon the alternating stimulation of H2O2 and Vc was examined. Then the cell adhesion, proliferation, and controlled detachment on honeycomb films were conducted. FINDINGS: The introduction of didodecyl selenide helps to form ordered honeycomb film, and Se atoms were found to located on the bottom, pore walls, and top surface of the film. The presence of didodecyl selenide not only greatly improves film biocompatibility by enhancing cell thioredoxin reductase activity, but also imparts the film with H2O2-/vitamin C-regulated tunable wettability that controls cell adhesion and detachment. H2O2 treatment produces a hydrophilic surface for cell adhesion and proliferation, whereas the addition of vitamin C generates hydrophobic surfaces and allows cells to detach while remaining alive with high activity.


Asunto(s)
Selenio , Adhesión Celular , Selenio/farmacología , Peróxido de Hidrógeno , Oxidación-Reducción , Ácido Ascórbico , Propiedades de Superficie
18.
Altern Ther Health Med ; 29(6): 112-119, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34936988

RESUMEN

Context: Pterygium, meaty eyes, is a disease that produces a triangular, conjunctival-epithelial, neovascularized overgrowth covering the cornea, which can cause vision loss. Histological characterization of Pterygium reveals the presence of proliferating fibroblasts (FBs) that remodel the extracellular matrix, with infiltration of immune cells, causing chronic inflammation. The fresh juice of Echeveria pallida E. Walther (Crassulaceae), mechanically extracted from the leaves, can be used to lubricate the eyes and remove Pterygium, even in advanced, degenerative ocular disease. Objective: This study aimed to explore the healing mechanisms of an ethanolic extract of E. pallida on pterygium-derived FBs, lymphocytes, and neutrophils. Design: The research team designed an in-vitro study. Primary cultures of FBs were obtained from fresh, surgical pterygium tissues, and neutrophils and mononuclear cells were purified from the peripheral blood of healthy donors. Intervention: An ethanolic extract of E. pallida was evaluated at 30, 50, 80, 100, 200, and 300 µg/mL-the intervention groups-for viability and proliferation of FBs and lymphocytes. The study included a negative control with no extract, and a positive control, Mitomycin C (MMC), used as a FB proliferation inhibitor and anti-inflammatory. Because some reports have suggested that DMSO at low concentrations can stimulate or inhibit lymphocyte proliferation depending on the cell type, the study also included a DMSO control. Outcome Measures: The measures included an analysis of E. pallida's effects on the proliferation and viability of FBs, the proliferation of human lymphocytes, and human neutrophil extracellular traps (NETs) production. NETs were induced using biochemical and microbiological stimuli-phorbol myristate acetate (PMA), hypochlorous acid (HOCl), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans-through fluorescence microscopy. Results: The ethanolic extract didn't affect the viability or proliferation of pterygium-derived FBs and human blood lymphocytes, but it showed significant inhibitory activity, from 100 µg/mL, on FB adhesion and the production of NETs. Conclusion: The study found scientific evidence that supports the effects of an extract of the medicinal plant E. pallida in inhibiting the adhesion of FBs derived from human pterygium and NET production.


Asunto(s)
Crassulaceae , Trampas Extracelulares , Fibroblastos , Extractos Vegetales , Pterigion , Fibroblastos/efectos de los fármacos , Neutrófilos , Adhesión Celular , Humanos , Crassulaceae/química , Extractos Vegetales/farmacología , Células Cultivadas
19.
Anat Rec (Hoboken) ; 306(12): 3033-3049, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36136292

RESUMEN

Cold coagulation and blood stasis (CCBS) syndrome is one of the common traditional Chinese medicine (TCM) syndromes of gynecological diseases. However, the molecular mechanism of CCBS syndrome is still unclear. Thus, there is a need to reveal the occurrence and regulation mechanism of CCBS syndrome, in order to provide a theoretical basis for the treatment of CCBS syndrome in gynecological diseases. The plasma proteins in primary dysmenorrhea (PD) patients with CCBS syndrome, endometriosis (EMS) patients with CCBS syndrome, and healthy women were screened using Label-free quantitative proteomics. Based on the TCM theory of "same TCM syndrome in different diseases," the differentially expressed proteins (DEPs) identified in each group were subjected to intersection mapping to obtain common DEPs in CCBS syndrome. The DEPs of gynecological CCBS syndrome in the intersection part were again cross-mapped with the DEPs of gynecological CCBS syndrome obtained by the research group according to the TCM theory of "different TCM syndromes in same disease" theory in the early stage, so as to obtain the DEPs of gynecological CCBS syndrome that were shared by the two parts. The common DEPs were subjected to bioinformatics analysis, and were verified by enzyme-linked immunosorbent assay (ELISA). A total of 67 common DEPs were identified in CCBS syndrome, of which 33 DEPs were upregulated and 34 DEPs were downregulated. The functional classification of DEPs involved in metabolic process, energy production and conversion, immune system process, antioxidant activity, response to stimulus, and biological adhesion. The subcellular location mainly located in the cytoplasm, nucleus, and extracellular. Gene ontology (GO) enrichment analysis showed that the upregulated DEPs mainly concentrated in lipid transport, cell migration, and inflammatory reaction, and the downregulated DEPs mostly related to cell junction, metabolism, and energy response. Protein domain enrichment analysis and clustering analysis revealed that the DEPs mainly related to cell proliferation and differentiation, cell morphology, metabolism, and immunity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis clustering analysis showed that the upregulated DEPs were involved in inflammation and oxidative damage, while the downregulated DEPs were involved in inflammation, cell adhesion, cell apoptosis, and metabolism. The results of ELISA showed significantly increased levels of Cell surface glycoprotein MUC18 (MCAM) and Apolipoprotein C1 (APOC1), and significantly decreased levels of Vasodilator-stimulated phosphoprotein (VASP), Fatty acid-binding protein 5 (FABP5), and Vinculin (VCL) in patients with CCBS syndrome compared with healthy women. We speculated that cold evil may affect the immune process, inflammatory response, metabolic process, energy production and conversion, oxidative damage, endothelial cell dysfunction, and other differential proteins expression to cause CCBS syndrome in gynecological diseases.


Asunto(s)
Estrés Oxidativo , Proteómica , Humanos , Femenino , Apoptosis , Adhesión Celular , Inflamación , Proteínas de Unión a Ácidos Grasos
20.
Psicol. ciênc. prof ; 43: e255712, 2023.
Artículo en Portugués | LILACS, INDEXPSI | ID: biblio-1529208

RESUMEN

Com o advento da covid-19, foi declarado estado de emergência de saúde pública e decretadas medidas de isolamento e distanciamento social para conter a propagação da doença. O Conselho Federal de Psicologia, considerando a importância do acolhimento seguro durante a pandemia, publicou a Resolução CFP nº 4/2020, permitindo que serviços psicológicos aconteçam de maneira remota. O presente estudo visa, através do Método da Cartografia, apresentar a construção de um setting on-line para intervenções grupais e os desafios na oferta de acolhimento e atendimento remoto. Foram ofertados grupos terapêuticos, por meio da plataforma Google Meet, para estudantes da Universidade Federal Rural do Rio de Janeiro. Um diário de bordo foi produzido para acompanhar as forças que atravessavam e constituíam o território e a experiência grupal remota. Compreendemos que o território-espaço-grupal-on-line era composto pelo espaço virtual em que nos reuníamos, pelos espaços individuais de cada integrante e pelas forças que os atravessavam. Observamos que nem sempre os participantes dispunham de um lugar privado, mas estiveram presentes no encontro com câmeras e áudios abertos e/ou fechados e/ou através do chat da videochamada. A participação no grupo funcionou como alternativa no momento de distanciamento social, sendo uma possibilidade para o atendimento psicológico em situações de dificuldade de encontros presenciais; entretanto, se mostrou dificultada em diversos momentos, pela falta de equipamentos adequados e instabilidade na internet, fatores que interferiram nas reuniões e impactaram na possibilidade de falar e escutar o que era desejado.(AU)


With the advent of COVID-19, a state of public health was declared, and measures of isolation and social distance to contain the spread of the disease was decreed. The Federal Council of Psychology, considering the importance of safe reception during the pandemic, published CFP Resolution No. 4/2020, allowing psychological services to happen remotely. This study narrates, via the Cartography Method, the experience of inventing an Online Setting for group reception. Therapeutic groups were offered, via Google Meet Platform, to students at the Federal Rural University of Rio de Janeiro. A logbook was produced to accompany the forces that crossed and constituted the territory and the remote group experience. We understand that the territoryspace-group-online was composed by the virtual-space that we gathered, by the individualspaces of each member and by the forces that crossed them. We observed that the participants did not always have a private place, but they were present at the meeting with open and/or closed cameras and audio and/or through the video call chat. Participation in the group worked as an alternative at the time of social distancing, being a possibility for psychological care in situations of difficulty in face-to-face meetings, however, it proved to be difficult at various times, due to the lack of adequate equipment and instability on the internet, factors that interfered in meetings and impacted the possibility of speaking and listening to what was desired.(AU)


La llegada de la COVID-19 produjo un estado de emergencia de salud pública, en el que se decretaron medidas de confinamiento y distanciamiento físico para contener la propagación de la enfermedad. El Consejo Federal de Psicología, considerando la importancia de la acogida segura durante la pandemia, publicó la Resolución CFP nº 4/2020, por la que se permite la atención psicológica remota. Este estudio tiene por objetivo presentar, mediante el método de la Cartografía, la elaboración de un escenario en línea para la intervención grupal y los desafíos en la oferta de acogida y atención remota. Grupos terapéuticos se ofrecieron, en la plataforma Google Meet, a estudiantes de la Universidad Federal Rural de Río de Janeiro. Se elaboró un diario para acompañar a las fuerzas que atravesaron y constituyeron el territorio y la experiencia remota del grupo. Entendemos que el territorio-espacio-grupo-en línea estaba compuesto por el espacio-virtual que reunimos, por los espacios individuales de cada integrante y por las fuerzas que los atravesaban. Observamos que los participantes no siempre tenían un lugar privado y que estaban presentes en la reunión con cámaras y audio abiertos y/o cerrados y/o por el chat de la videollamada. La participación en el grupo funcionó como una alternativa en el momento del distanciamiento físico y revela ser una posibilidad de atención psicológica en situaciones de dificultad en los encuentros presenciales, sin embargo, se mostró difícil en varios momentos, ya sea por la falta de medios adecuados o por inestabilidad en Internet, factores que interferían en las reuniones e impactaban en la posibilidad de hablar y escuchar lo que se deseaba.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Psicología , Actitud , Servicios de Contestadora , Intervención basada en la Internet , Teletrabajo , COVID-19 , Ansiedad , Satisfacción Personal , Preceptoría , Ubicación de la Práctica Profesional , Psicoanálisis , Psicología Social , Calidad de Vida , Seguridad , Identificación Social , Valores Sociales , Socialización , Factores Socioeconómicos , Habla , Estudiantes , Enseñanza , Desempleo , Universidades , Trabajo , Conducta , Conducta y Mecanismos de Conducta , Horas de Trabajo , Actitud hacia los Computadores , Aplicaciones de la Informática Médica , Aflicción , Padres Solteros , Familia , Áreas de Influencia de Salud , Adhesión Celular , Comunicación Celular , Cuarentena , Control de Enfermedades Transmisibles , Salud Mental , Esperanza de Vida , Precauciones Universales , Control de Infecciones , Empleos Subvencionados , Comunicación , Exámenes Obligatorios , Confidencialidad , Privacidad , Imágenes en Psicoterapia , Procesos Psicoterapéuticos , Internet , Intervención en la Crisis (Psiquiatría) , Autonomía Personal , Muerte , Confianza , Códigos de Ética , Depresión , Contaminación del Aire , Escolaridad , Prevención de Enfermedades , Centros de Ocio y Convivencia , Capacitación Profesional , Docentes , Relaciones Familiares , Miedo , Inteligencia Emocional , Reinserción al Trabajo , Esperanza , Habilidades Sociales , Ajuste Emocional , Optimismo , Estilo de Vida Saludable , Equilibrio entre Vida Personal y Laboral , Tutoría , Tristeza , Respeto , Solidaridad , Distrés Psicológico , Integración Social , Modelo Transteórico , Intervención Psicosocial , Esfuerzo de Escucha , Cohesión Social , Pertenencia , Entrenamiento Cognitivo , Diversidad, Equidad e Inclusión , Bienestar Psicológico , Tareas del Hogar , Humanidades , Individualidad , Trastornos del Inicio y del Mantenimiento del Sueño , Relaciones Interpersonales , Aprendizaje , Acontecimientos que Cambian la Vida , Motivación , Apego a Objetos
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