RESUMO
The skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials.
Assuntos
Hidrogéis , Pele , Hidrogéis/química , Materiais Biocompatíveis/química , Polímeros , Membrana CelularRESUMO
Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials.
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Stem cells and their microenvironment interact cooperatively to dictate their fates. Biomaterials are dynamically remodeled by stem cells, and stem cells sense and translate the changes into cell fate decisions. We have previously reported that adaptive biomaterials composed of fibronectin inserted into protein nanosheets at a liquid interface enhance neuronal differentiation of human mesenchymal stem cells (hMSCs). However, we could not decouple clearly the effect of ligand density from that of fibrillary structure on cellular function and fate. Here we present an adaptive biomaterial based on two-dimensional networks of protein nanofibrils at a liquid-liquid interface. Compared with flat protein nanosheets, this biomaterial enhances neuronal differentiation of hMSCs through a signaling mechanism involving focal adhesion kinase. Lipid raft microdomains in plasma membrane are found to play a central role in which hMSCs rapidly adapt to the dynamic microenvironment at the fluid interface. Our finding has substantial implications for regenerative medicine and tissue engineering.
Assuntos
Células-Tronco Mesenquimais , Materiais Biocompatíveis/química , Diferenciação Celular/fisiologia , Humanos , Microdomínios da Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual/métodosRESUMO
The flame-retardant polyamide 66 composites (FR-PA66) were prepared by in situ loading of amino-functionalized polyphosphazene microspheres (HCNP), which were synthesized in the laboratory and confirmed by a Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM), and transmission electron microscope (TEM). The thermal stabilities and flame retardancy of FR-PA66 were measured using thermogravimetric analysis (TGA), a thermogravimetric infrared instrument (TG-IR), the limiting oxygen index (LOI), the horizontal and vertical combustion method (UL-94), and a cone calorimeter. The results illustrate that the volatile matter of FR-PA66 mainly contains carbon dioxide, methane4, and water vapor under heating, accompanied by the char residue raising to 14.1 wt% at 600 °C and the value of the LOI and UL-94 rating reaching 30% and V-0, respectively. Moreover, the addition of HCNP decreases the peak of the heat release rate (pHRR), total heat release (THR), mass loss (ML), and total smoke release (TSR) of FR-PA66 to 373.7 kW/m2, 106.7 MJ/m2, 92.5 wt%, and 944.8 m2/m2, respectively, verifying a significant improvement in the flame retardancy of PA66.
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Three previously undescribed seco-dammarane triterpenoid glycosides O-Q (1-3) along with two known compounds (4 and 5) were isolated and characterized from the leaves of Cyclocarya paliurus. Their structures were determined by comprehensive analysis of 1 D, 2 D NMR and HRESIMS data. Compounds 1-5 were evaluated for their inhibitory effects against human pancreatic tumor (ASPC-1), human gastric carcinoma (SNU5), liver hepatocellular carcinoma (HEPG-2) and human colon tumor (HCT116) cell lines. Among them cyclocarioside P (2) showed somewhat inhibitory activity towards those tumor cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Juglandaceae/química , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Células HCT116 , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Folhas de Planta/química , DamaranosRESUMO
Three previously undescribed dammarane triterpenoid glycosides (1-3) along with five known analogues (4-8) were isolated from the leaves of Cyclocarya paliurus. Their structures and configurations were determined on the basis of comprehensive spectroscopic analyses, chemical hydrolysis and DFT GIAO 13C NMR calculation. All the isolates were evaluated cytotoxic activities against seven human cancer cell lines (MCF-7, PC-3, Du145, NCI-H1975, PC-9, SKVO3 and HepG2). Moreover, compound 4 showed a wide spectrum of cytotoxicity against human cancer cells with IC50 values ranging from 11.31 to 29.51 µM.
Assuntos
Juglandaceae , Triterpenos , Glicosídeos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta , Triterpenos/farmacologiaRESUMO
Eight new prenylflavonol glycosides (1-8), along with five known analogues (9-13) were isolated from the n-butanol extract of the dried leaves of Cyclocarya paliurus (family Juglandaceae) for the first time. The structures of these compounds were characterized by comprehensive analysis of 1D, 2D NMR, HRESIMS, UV data and acid hydrolysis. In bioassay, all these thirteen prenylflavonol glycosides exhibited inhibitory effects on xanthine oxidase (XOD) activity. Especially compounds 2 and 7, showed outstanding IC50 values of 31.81 ± 2.20 and 29.71 ± 3.69 µM, respectively.
Assuntos
Inibidores Enzimáticos/farmacologia , Flavonóis/farmacologia , Glicosídeos/farmacologia , Juglandaceae/química , Folhas de Planta/química , Xantina Oxidase/antagonistas & inibidores , Extratos Vegetais/química , Análise Espectral/métodos , Relação Estrutura-AtividadeRESUMO
Four new rarely occurred seco-dammarane triterpenoid glycosides (1-4) and four new dammarane triterpenoid glycosides (5-8), along with four known triterpenoids (9-12), were isolated from the 70% ethanol extract of the leaves of Cyclocarya paliurus (family Juglandaceae). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR and HRESIMS data, together with chemical analysis and DFT GIAO 13C NMR calculation. In bioassay, compounds 5-8 significantly increased glucose consumption in 3T3-L1 adipocytes, which could be the bioactive constituents for the anti-diabetes effect of the traditional usage of C. paliurus.
Assuntos
Adipócitos/efeitos dos fármacos , Glicosídeos/farmacologia , Hipoglicemiantes/farmacologia , Juglandaceae/química , Triterpenos/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Relação Dose-Resposta a Droga , Glucose/metabolismo , Glicosídeos/química , Glicosídeos/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Camundongos , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of cancer worldwide, with a poor prognosis. The aim of the present study was to investigate the effect of cisatracurium (Cis) on epithelial-to-mesenchymal transition (EMT) in ESCC and its potential mechanism of action. In the present study, Cis was used to treat ECA-109 cells, with cell proliferation measured by a Cell Counting Kit-8 assay and the expression of TGF-ß and phospho-Smad2/3 detected by western blotting. TGF-ß was then applied to induce EMT. Flow cytometry, wound healing and Transwell assays were used to evaluate cell proliferation, apoptosis, invasion and migration. In addition, cell cycle-related proteins, including cyclin D1, p53 and p21, and EMT-associated proteins, including E-cadherin (E-cad), N-cadherin (N-cad), Vimentin and Slug, were examined by western blot analysis. The results revealed that Cis inhibited the proliferation and promoted apoptosis of ESCC cells. Following treatment with Cis, the expression of TGF-ß and phosphorylation of Smad2/3 were downregulated. Cis also suppressed cancer cell invasion and migration induced by TGF-ß. In addition, the expression levels of cyclin D1 were decreased, accompanied by increased p53 and p21 expression. In addition, the expression level of E-cad was increased, whereas N-cad, Vimentin and Slug were significantly reduced. Taken together, the results of the present study revealed that exposure of ESCC cells to Cis inhibited EMT and reduced cell invasion and metastasis through the TGF-ß/Smad signaling pathway.
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Cardiovascular disease is the leading cause of death worldwide. Dysregulation of microRNAs (miRNAs) has been found to be associated with cardiovascular diseases such as atherosclerosis. In the present study, we examined the role of miR-147b in the proliferation and migration of vascular smooth muscle cells (VSMCs). Quantitative real-time PCR was performed to determine the expression levels of miR-147b and Yin Yang 1 (YY1) mRNA. CCK-8, transwell migration and wound healing assays were used to determine cell proliferation and migration of VSMCs, respectively. Luciferase reporter assay confirmed the downstream target of miR-147b. The protein level of YY1 was measured by western blot analysis. Platelet-derived growth factor-bb (PDGF-bb) treatment promoted cell proliferation and increased miR-147b expression in VSMCs. Overexpression of miR-147b enhanced cell proliferation and migration of VSMCs, while knock-down of miR-147b suppressed cell proliferation and migration of VSMCs or PDGF-bb-treated VSMCs. Further, bioinformatics prediction and luciferase reporter assay showed that YY1 was a downstream target of miR-147b, and miR-147b negatively regulated the mRNA and protein expression of YY1 in VSMCs. Overexpression of YY1 inhibited cell proliferation and migration of VSMCs and attenuated the effects of miR-147b overexpression on cell proliferation and migration. In addition, overexpression of miR-147b increased the Wnt/ß-catenin signaling activities in VSMCs. In conclusion, our results suggest that miR-147b plays important roles in the control of cell proliferation and migration of VSMCs possibly via targeting YY1.
Assuntos
Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Miócitos de Músculo Liso/metabolismo , Via de Sinalização Wnt/genética , Fator de Transcrição YY1/genética , Regiões 3' não Traduzidas/genética , Sequência de Bases , Becaplermina/farmacologia , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Músculo Liso Vascular/citologia , Homologia de Sequência do Ácido Nucleico , Fator de Transcrição YY1/metabolismoRESUMO
Vitamin D3 has been reported to be an immunity modulator and high levels of vitamin D3 are correlated with a decreased risk for developing diseases in the central nervous system. Astrocytes are important immune cells and contribute toward inflammation during neurological diseases. The vitamin D receptor has been reported to be expressed in astrocytes; however, the effect of vitamin D3 on astrocyte activation has not been studied. Here, we found that lipopolysaccharide stimulation in astrocytes could enhance the expression of vitamin D receptor and Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form. Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis factor-α, interleukin-1ß, vascular endothelial growth factor, and also TLR4 in activated astrocytes. Astrocyte activation was further found to be suppressed after the administration of vitamin D3 in neonatal rats injected with lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin D3 in astrocytes after lipopolysaccharide stimulation. Considering the function of reactive astrocytes in augmenting inflammatory response in neurodegeneration and brain injury, the finding that vitamin D3 administration may inhibit astrocyte activation may be potentially useful for the treatment of central nervous system disorders.