Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 157
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Colloids Surf B Biointerfaces ; 185: 110608, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31707225

RESUMO

Drug content and releasing rate are the main determining factors for the drug delivery systems (DDSs). Here, doxorubicin dimer (D-DOXcar) was synthesized as drug-drug conjugate prodrug with high drug content of 86%, via an acid-triggered hydrolysable carbamate linker. The prodrug nanoparticles (D-DOXcar-NP) with different diameters were prepared as drug self-delivery system (DSDS) for intracellular pH-triggered slow release. They showed size- and concentration-dependent pH-triggered slow DOX release. For the D-DOXcar-sNP with smaller diameter, the cumulative release ratio reached 25.6% at pH 5.0 within 60 h. The MTT results demonstrated that the proposed DSDS showed similar tumor inhibition regardless of carboxylesterases, and an enhanced anti-tumor efficacy on the HepG2 cells in comparison with the free DOX.

2.
Chem Commun (Camb) ; 55(93): 13991-13994, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31687672

RESUMO

We highlight that sufficient hydration of non-crystallized RNA could provide high-resolution solid-state NMR (SSNMR) spectra, with similar spectral quality to the crystallized RNA. This leads to a greatly simplified RNA preparation approach by ethanol precipitation for high-resolution SSNMR studies. It will greatly broaden the scope of SSNMR applications to the characterization of RNAs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31681945

RESUMO

Cardiac hypertrophy is considered to be a leading factor in heart function-related deaths. In this study, we explored the potential mechanism underlying cardiac hypertrophy induced by isoproterenol. Our results showed that isoproterenol induced cardiac hypertrophy in AC16 cells, as reflected by the increased cell surface area and increased hypertrophic markers, which was accompanied by increased ubiquitin-protein ligase E3a (UBE3A) expression. Moreover, UBE3A knockdown by siRNAs accelerated cardiac hypertrophy, suggesting that increased UBE3A expression induced by isoproterenol might be a protective response and UBE3A might be a protective factor against cardiac hypertrophy. Our study also revealed that UBE3A knockdown increased the protein expression of the TLR4/MMP-9 pathway that has been shown to be associated with cardiac hypertrophy, which suggested that UBE3A-mediated protection is likely to be associated with the blockade of the TLR4/MMP-9 signaling pathway. UBE3A might be thus a potential target gene for the treatment of cardiac hypertrophy.

4.
Microbiologyopen ; : e940, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588663

RESUMO

OBJECTIVE: To find antagonistic strains in the respiratory tract having bacteriostatic properties against common pathogens. METHODS: The oropharyngeal microbiota of five healthy children aged 4-6 years were collected and α-hemolytic bacteria screened on 15% sheep blood agar. Bacteriostatic effects of the isolated α-hemolytic bacteria on Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes were evaluated by the Oxford cup method. Antagonistic strains were identified by mass spectrometry, and the16S rDNAs were sequenced, and their best bacteriostatic concentrations and antagonistic spectra for Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, Acinetobacter Baumanii, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes were evaluated. RESULTS: Of 300 isolated α-hemolytic bacterial clones, four exhibited bacteriostatic activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Mass spectrometric analyses revealed that two of them were Streptococcus mitis and two others were Streptococcus parasanguinis strains. Further tests showed that all 4 antagonistic strains also had bacteriostatic effects on Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, and Acinetobacter Baumanii, and the mode of action was not mediated by lactic acid production. CONCLUSION: Four antagonistic Streptococcus strains derived from oropharyngeal microbiotas showed bacteriostatic effects on pathogens and may be involved in pharyngeal microbiome homeostasis.

5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 378-383, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512829

RESUMO

OBJECTIVE: To investigate the effect of the long chain non-coding RNA H19 (lncRNA H19) on the invasion and migration of oral cancer cells and its related molecular mechanism. METHODS: The expression levels of lncRNA H19, miR-107, and cyclin-dependent kinase 6 (CDK6) in the immortalized oral epithelial cell line HIOEC and the oral cancer cell line CAL27 were detected by real-time quantitative polymerase chain reaction. CAL27 cells were transfected with siRNA H19, miR-107 mimics, pcDNA H19, or anti-miR-107, and the effects of H19 and miR-107 on the invasion and migration of cells were examined via Transwell assay. The TargetScan database predicted the targeting of H19, miR-107, and CDK6. Double luciferase reporter gene assay was performed to detect interactions among H19, miR-107, and CDK6. Western blot analysis was conducted to examine the effects of H19 and miR-107 on the protein level of the target gene CDK6. RESULTS: Compared with that in HIOEC cells, the expression of H19 was significantly increased in CAL27 cells (P<0.05). After transfection with siRNA H19, the expression of H19 decreased, and the invasion and migration ability of CAL27 cells were inhibited (P<0.05). H19 could bind specifically to the 3'-UTR of miR-107 to modulate the expression of miR-107. Compared with that in HIOEC cells, the expression of miR-107 significantly decreased in CAL27 cells (P<0.05). The expression of miR-107 increased after transfection with siRNA H19, and anti-mir-107 co-transfection could promote the invasion and migration ability of siRNA H19 in CAL27 cells (P<0.05). Compared with that in HIOEC cells, CDK6 expression significantly increased in CAL27 cells (P<0.05), and the expression level of the gene was coregulated by H19 and miR-107 (P<0.05). CONCLUSIONS: lncRNA H19 plays an important role in the development of oral cancer. It can regulate the invasion and migration of oral cancer cells by targeting the miR-107/CDK6 signaling axis.


Assuntos
MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos
6.
Macromol Biosci ; 19(9): e1900124, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31310440

RESUMO

Multivalent carbohydrate-lectin interactions play a crucial role in bacterial infection. Biomimicry of multivalent glycosystems represents a major strategy in the repression of bacterial growth. In this study, a new kind of glycopeptide (Naphthyl-Phe-Phe-Ser-Tyr, NMY) scaffold with mannose modification is designed and synthesized, which is able to perform supramolecular self-assembly with the assistance of catalytic enzyme, and present multiple mannose ligands on its self-assembled structure to target mannose-binding proteins. Relying on multivalent carbohydrate-lectin interactions, the glycopeptide hydrogel is able to bind Escherichia coli (E. coli) in high specificity, and result in bacterial adhesion, membrane disruption and subsequent cell death. In vivo wound healing assays reveal that this glycopeptide hydrogel exhibits considerable potentials for promoting wound healing and preventing E. coli infection in a full-thickness skin defect mouse model. Therefore, through a specific mannose-lectin interaction, a biocompatible hydrogel with inherent antibacterial activity against E. coli is achieved without the need to resort to antibiotic or antimicrobial agent treatment, highlighting the potential role of sugar-coated nanomaterials in wound healing and control of bacterial pathogenesis.

7.
J Agric Food Chem ; 67(29): 8227-8234, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31299148

RESUMO

The mechanisms underlying neurodegenerative diseases are not fully understood yet. However, an increasing amount of evidence has suggested that these disorders are related to oxidative stress. We reported herein that lipoamide (LM), a neutral amide derivative of lipoic acid (LA), could resist oxidative stress-mediated neuronal cell damage. LM is more potent than LA in alleviating hydrogen peroxide- or 6-hydroxydopamine-induced PC12 cell injury. Our results reveal that LM promotes the nuclear accumulation of NFE2-related factor 2 (Nrf2), following with the activation of expression of Nrf2-governed antioxidant and detoxifying enzymes. Notably, silencing Nrf2 gene annuls the protection of LM, which demonstrates that Nrf2 is engaged in this cytoprotection. Our findings suggest that LM might be used as a potential therapeutic candidate for oxidative stress-related neurological disorders.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/análogos & derivados , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos , Ácido Tióctico/farmacologia
8.
Nat Commun ; 10(1): 2745, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227705

RESUMO

Small molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.


Assuntos
Descoberta de Drogas/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Sondas Moleculares/química , Tiorredoxina Redutase 1/metabolismo , Animais , Produtos Biológicos/farmacologia , Misturas Complexas , Dissulfetos/química , Corantes Fluorescentes/metabolismo , Células HeLa , Ensaios de Triagem em Larga Escala/métodos , Humanos , Microscopia Intravital/métodos , Microscopia de Fluorescência/métodos , Sondas Moleculares/metabolismo , Oxirredução , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Tiorredoxina Redutase 1/antagonistas & inibidores , Tiorredoxina Redutase 1/genética
9.
Science ; 364(6445): 1057-1062, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31197007

RESUMO

Nanoporous two-dimensional materials are attractive for ionic and molecular nanofiltration but limited by insufficient mechanical strength over large areas. We report a large-area graphene-nanomesh/single-walled carbon nanotube (GNM/SWNT) hybrid membrane with excellent mechanical strength while fully capturing the merit of atomically thin membranes. The monolayer GNM features high-density, subnanometer pores for efficient transport of water molecules while blocking solute ions or molecules to enable size-selective separation. The SWNT network physically separates the GNM into microsized islands and acts as the microscopic framework to support the GNM, thus ensuring the structural integrity of the atomically thin GNM. The resulting GNM/SWNT membranes show high water permeance and a high rejection ratio for salt ions or organic molecules, and they retain stable separation performance in tubular modules.

10.
Environ Pollut ; 246: 972-979, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31126003

RESUMO

In order to investigate the relationship between air pollution and the respiratory tract microbiota, 114 healthy volunteers aged 18-21 years were selected during the winter heating period in Northeast China; 35 from a lightly polluted region (group A), 40 from a moderately polluted region (group B) and 39 from a heavily polluted region (group C). Microbial genome DNA was extracted from throat swab samples to study the oral flora composition of the volunteers by amplifying and sequencing the V3 regions of prokaryotic 16S rRNA. Lung function tests were also performed. The relative abundance of Bacteroidetes and Fusobacteria were significantly lower and Firmicutes Proteonacteria and Actinobacteria higher in participants from polluted regions. Within bacteria classes, Bacterioida abundance was lower and Clostridia abundance higher in polluted areas, which was also reflected in the order of abundance. In samples from region C, the abundance of Prevotellaceae, Veillonellaceae, Porphyromonadaceae, Fusobacteriaceae Paraprevollaceae and Flavobacteriaceae were lowest among the 3 regions studied, whereas the abundance of Lachnospiraceae and Ruminococcaceae were the highest. From group A to group C, the relative class abundances of Prevotella, Veillonella, Fusobacterium, Camphylobacter and Capnocytophaga Porphyromonas, Peptostreptococcus and Moraxella became lower in polluted areas. Pulmonary function correlated with air pollution and the oropharyngeal microbiota differed within regions of high, medium and low air pollution. Thus, during the winter heating period in Northeast China, the imbalance of the oropharyngeal microbiota might be caused by air pollution and is likely associated with impairment of lung function in young people.


Assuntos
Poluição do Ar/análise , Bactérias/classificação , Microbiota , Sistema Respiratório/microbiologia , Adolescente , Bactérias/isolamento & purificação , Bacteroidetes/isolamento & purificação , China , Feminino , Calefação , Humanos , Masculino , RNA Ribossômico 16S/química , Estações do Ano , Análise de Sequência de DNA , Adulto Jovem
11.
Anal Chem ; 91(9): 6057-6063, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30943013

RESUMO

Hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) is a complementary technique to reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and has been widely used to expand the coverage of the metabolome in MS-based metabolomics. However, the use of HILIC retention time (HILIC RT) in metabolites annotation is quite limited because of its poor reproducibility. Here, we developed a method to calculate the retention index in HILIC (HILIC RI) for calibration of HILIC RT. In this method, a mixture of 2-dimethylaminoethylamine (DMED)-labeled fatty acid standards with carbon chain length from C2 to C22 were selected as calibrants to establish a linear calibration equation between HILIC RT and carbon number for the calculation of HILIC RI. The calculated HILIC RIs based on a regression equation could efficiently calibrate the retention time shifts for 28 DMED-labeled carboxyl standards and DMED-labeled carboxyl metabolites in rat urine, serum and feces on a HILIC column with different gradient elution conditions. Furthermore, the developed HILIC RI strategy was applied to RT calibration of screened metabolites, the annotation of isomers in HILIC-MS-based metabolomics analysis for real samples, and the correction of isotope effects in chemical isotope labeling HILIC-MS analysis. Taken together, the resulting HILIC RI strategy is a promising analytical technique to improve the accuracy of metabolite annotation; it would be widely used in HILIC-MS-based metabolome analysis.

12.
J Int Med Res ; 47(5): 2145-2156, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30966824

RESUMO

OBJECTIVE: This study was performed to assess the clinical feasibility, safety, and effectiveness of a computed tomography (CT)-guided cyanoacrylate injection system and investigate the relationship between clinical features and pathologic characteristics of diminutive pulmonary lesions. METHODS: In total, 115 pulmonary nodules from 113 patients (63 female, 50 male) with a diameter of <20 mm were percutaneously localized with a CT-guided cyanoacrylate injection system and then resected. RESULTS: Of the pure ground-glass opacities (GGOs), 16.0% were atypical adenomatous hyperplasia (AAH), 18.7% were adenocarcinoma in situ (AIS), 49.3% were lung adenocarcinoma (ADC), and 16.0% were benign inflammatory fibrosis/fibrotic scars. Of the mixed GGOs, 18.2% were AAH, 22.7% were AIS, 22.7% were ADC, and 36.4% were benign lesions. Lesions of >10 mm and those located in relation to vessels were significantly more likely to be malignant. The success rate of both the cyanoacrylate injection system and video-assisted thoracoscopic surgery was 100% with no severe complications. CONCLUSIONS: Preoperative localization of small pulmonary nodules using a cyanoacrylate injection system is a safe, simple, and useful technique.


Assuntos
Cianoacrilatos/administração & dosagem , Injeções , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Cianoacrilatos/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Carga Tumoral
13.
Toxicol Appl Pharmacol ; 370: 106-116, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30898620

RESUMO

The selenoprotein thioredoxin reductase (TXNRD) is a promising therapeutic target for cancer. To discover novel TXNRD inhibitors, a library of α, ß-unsaturated carbonyl compounds were applied in structure-based virtual screening for the selection of hit compounds. Fifteen top-ranked compounds were further validated experimentally, exhibiting potent inhibition of TXNRD and remarkable cytotoxicity to cancer cells. The further binding mode analysis indicated that multiple noncovalent interactions between the inhibitors and the active pocket of TXNRD facilitated the formation of covalent bonds between the Sec498 on TXNRD and the α, ß-unsaturated carbonyl groups on inhibitors. Results from both simulations and experiments demonstrated that Sec498 is the prime interaction site for the inhibition of TXNRD. Taking compound 7 as an example, the inhibition of TXNRD by compounds promoted oxidative stress-mediated apoptosis of cancer cells. Given these findings, novel TXNRD inhibitors may be discovered and introduced to the growing fields of small molecule drugs against TXNRD.

14.
Cell Cycle ; 18(6-7): 682-695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30784343

RESUMO

BACKGROUND: Atherosclerosis (AS) is a major risk factor for cardiovascular disease. microRNAs play a key role in gene regulation in the formation and development of atherosclerotic plaques. Herein, the role and target gene of miR-185 in AS were explored. MATERIALS AND METHODS: Cell viability, migration and invasion were examined by cell counting kit-8 (CCK-8) and transwell assay. The relative luciferase activity was measured by luciferase reporter assay. The levels of miR-185, STIM1, vascular endothelial growth factor (VEGF) and matrix metalloprotein-9 (MMP-9) were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. RESULTS: The results revealed that ox-LDL decreased miR-185 expression, and enhanced STIM1 expression in MOVAS cells, as well promoted cell viability, migration and invasion. 3'-UTR of STIM1 contained miR-185 binding site according to the Targetscan. miR-185 silencing or STIM1 overexpression promoted the viability, migration and invasion of ox-LDL-induced MOVAS cells. miR-185 overexpression or STIM1 silencing had the opposite effect. Besides, miR-185 silencing up-regulated the levels of VEGF and MMP-9 in vitro, and increased the lesions of arterial wall tissues and STIM1 positive rate in vivo. However, STIM1 silencing reversed these effects. CONCLUSIONS: Sum up, STIM1 was a potential target gene of miR-185 in AS. Knockdown of miR-185 facilitated the progression of AS through enhancing cell proliferation, migration and invasion via targeting STIM1. The research provides a novel view of miR-185/STIM1 axis function in AS development, and this targeting method may prevent and treat AS.

15.
Med Res Rev ; 39(1): 5-39, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29727025

RESUMO

Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Mamíferos/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Animais , Antineoplásicos/química , Inibidores Enzimáticos/química , Humanos , Bibliotecas de Moléculas Pequenas/química , Tiorredoxina Dissulfeto Redutase/metabolismo
16.
Materials (Basel) ; 11(11)2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30405028

RESUMO

The high moisture sensitivity of feather keratin/polyvinyl alcohol/tris(hydroxymethyl)aminomethane (FK/PVA/Tris) blend films hinders their application in the packaging field. Thus, in order to improve the water resistance and mechanical properties of such blend films, we attempted cross-linking the blend film with cross-linking agents such as transglutaminase (TG), CaCl2, and genipin. Obvious differences in the morphology of the blended films were observed by scanning electron microscopy before and after cross-linking, indicating that cross-linking can inhibit the phase separation of the blend film. Conformational changes in the blend films after cross-linking were detected by Fourier transform infrared spectroscopy. Importantly, from examination of the total soluble mass, contact angle measurements, and water vapor permeability tests, it was apparent that cross-linking greatly improved the water resistance of the blend films, in addition to enhancing the mechanical properties (i.e., tensile strength and elongation at break). However, cross-linking was also found to reduce the oxygen barrier properties of the blend films. Therefore, cross-linking appears to be an effective method for promoting the application of FK/PVA/Tris blend films in the packaging field.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30481260

RESUMO

Heart failure (HF) induced by ischemia myocardial infarction (MI) is one of the major causes of morbidity and mortality all around the world. Atorvastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, has been demonstrated to benefit patients with ischemic or non-ischemic-induced HF, but the mechanism is still poorly understood. Increasing evidence indicates that lncRNAs play important role in variety of human disease. However, the role and underlying molecular mechanisms remain largely unclear. In our work, we applied 0.5% O2 to generate a hypoxia cardiac progenitor cell (CPC) model. Then, CCK8 and EdU assays were employed to investigate the role of atorvastatin in hypoxia CPC cell model. We found that hypoxia inhibits CPC viability and proliferation through modulating MEG3 expression, while atorvastatin application can protect CPCs from hypoxia-induced injury through inhibiting MEG3 expression. Then, we demonstrated that repression of MEG3 inhibited the hypoxia-induced injury of CPCs and overexpression of MEG3 inhibited the protective effect of atorvastatin in the hypoxia-induced injury of CPCs. Furthermore, our study illustrated that atorvastatin played its role in CPC viability and proliferation by modulating the expression of HMGB1 through the MEG3/miR-22 pathway. Our study, for the first time, uncovered the molecular mechanism of atorvastatin's protective role in cardiomyocytes under hypoxia condition, which may provide an exploitable target in developing effective therapy drugs for MI patients.

18.
Adv Healthc Mater ; : e1801043, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30485718

RESUMO

Silk fibroin (SF) from Bombyx mori is a promising natural material for the synthesis of biocompatible and biodegradable hydrogels for use in biomedical applications from tissue engineering to drug delivery. However, weak gelation performance and the lack of biochemical cues to trigger cell proliferation and differentiation currently significantly limit its application in these areas. Herein, a biofunctional hydrogel containing SF (2.0%) and a small peptide gelator (e.g., NapFFRGD = 1.0 wt%) is generated via cooperative molecular self-assembly. The introduction of NapFFRGD to SF is shown to significantly improve its gelation properties by lowering both its threshold gelation concentration to 2.0% and gelation time to 20 min under physiological conditions (pH = 7.4, 37 °C), as well as functionalizing the SF hydrogel with cell-adhesive motifs (e.g., RGD). Besides mediating cell adhesion, the RGD ligands incorporated within the SF-RGD gel promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells encapsulated within the gel matrix, leading to bone regeneration in a mouse calvarial defect model, compared with a blank SF gel (2.0%, pH = 7.4). This work suggests that SF could be easily tailored with bioactive peptide gelators to afford bioactive hydrogels with favorable microenvironments for tissue regeneration applications.

19.
Biomed Pharmacother ; 108: 1062-1069, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372806

RESUMO

Disulfiram (DSF), widely used for treating alcohol abuse, is a promising antitumour drug that inhibits tumour cell viability, reverses cancer drug resistance and induces apoptosis. However, its potential side effects on cardiomyocytes remain unknown. This study demonstrated that DSF can not only inhibit cardiomyocyte viability and activity but also promote cell apoptosis. Furthermore, we revealed that cardiomyocytes were more sensitive to DSF than cancer cells. Moreover, the expression of STAT3, a key regulator of cardiomyocyte viability, was significantly down-regulated in cardiomyocytes treated with DSF. Finally, we also used experimental comparisons to indicate that PEG is a promising solvent for decreasing the adverse side effects of DSF, thereby expanding its potential range of clinical applications.

20.
Acta Biochim Biophys Sin (Shanghai) ; 50(11): 1121-1130, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30307477

RESUMO

Apoptosis is involved in the death of cardiac progenitor cells (CPCs) after myocardial infarction (MI) in the heart. The loss of CPCs results in infarct scar and further deterioration of the heart function. Though stem cell-based therapy provides an effective approach for heart function recovery after MI, the retention of CPCs in the infarcted area of the heart is the main barrier that limits its promising therapy. Therefore, the underlying mechanisms of CPC apoptosis in hypoxia are important for the development of new therapeutic targets for MI patients. In this work, we found that the expression of high-mobility group box 1(HMGB1) was upregulated in CPCs under hypoxia conditions. Further study demonstrated that HMGB1 was regulated by DNA methyltransferases 1 (DNMT1) via changing the methylation state of CpGs in the promoter of HMGB1 in CPCs during hypoxia process. Additionally, mitogen-activated protein kinase (MAPK) signaling pathway was found to be involved in regulating DNMT1/HMGB1-mediated CPC apoptosis in hypoxia process. In conclusion, our findings demonstrate a novel regulatory mechanism for CPC apoptosis and proliferation under hypoxia conditions, which may provide a new therapeutic approach for MI patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA