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1.
Biomacromolecules ; 24(5): 2342-2355, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-37094104

RESUMEN

Ideal tissue-engineered skin scaffolds should possess integrated therapeutic effects and multifunctionality, such as broad-spectrum antibacterial properties, adjustable mechanical properties, and bionic structure. Acellular dermal matrix (ADM) has been broadly used in many surgical applications as an alternative treatment to the "gold standard" tissue transplantation. However, insufficient broad-spectrum antibacterial and mechanical properties for therapeutic efficacy limit the practical clinical applications of ADM. Herein, a balanceable crosslinking approach based on oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was developed for converting ADM into on-demand versatile skin scaffolds for integrated infected wounds therapy. Comprehensive experiments show that different oxidation degrees of OHTCC have significative influences on the specific origins of OHTCC-crosslinked ADM scaffolds (OHTCC-ADM). OHTCC with an oxidation degree of about 13% could prosperously balance the physiochemical properties, antibacterial functionality, and cytocompatibility of the OHTCC-ADM scaffolds. Owing to the natural features and comprehensive crosslinking effects, the proposed OHTCC-ADM scaffolds possessed the desirable multifunctional properties, including adjustable mechanical, degradable characteristics, and thermal stability. In vitro/in vivo biostudies indicated that OHTCC-ADM scaffolds own well-pleasing broad-spectrum antibacterial performances and play effectively therapeutic roles in treating infection, inhibiting inflammation, promoting angiogenesis, and promoting collagen deposition to enhance the infected wound healing. This study proposes a facile balanceable crosslinking approach for the design of ADM-based versatile skin scaffolds for integrated infected wounds therapy.


Asunto(s)
Dermis Acelular , Piel Artificial , Cicatrización de Heridas , Colágeno , Andamios del Tejido
2.
Biomacromolecules ; 24(3): 1483-1496, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36802497

RESUMEN

The repair of wound damage has been a common problem in clinic for a long time. Inspired by the electroactive nature of tissues and the electrical stimulation of wounds in clinical practice, the next generation of wound therapy with self-powered electrical stimulator is expected to achieve the desired therapeutic effect. In this work, a two-layered self-powered electrical-stimulator-based wound dressing (SEWD) was designed through the on-demand integration of the bionic tree-like piezoelectric nanofiber and the adhesive hydrogel with biomimetic electrical activity. SEWD has good mechanical properties, adhesion properties, self-powered properties, high sensitivity, and biocompatibility. The interface between the two layers was well integrated and relatively independent. Herein, the piezoelectric nanofibers were prepared by P(VDF-TrFE) electrospinning, and the morphology of the nanofibers was controlled by adjusting the electrical conductivity of the electrospinning solution. Benefiting from its bionic dendritic structure, the prepared piezoelectric nanofibers had better mechanical properties and piezoelectric sensitivity than native P(VDF-TrFE) nanofibers, which can convert tiny forces into electrical signals as a power source for tissue repair. At the same time, the designed conductive adhesive hydrogel was inspired by the adhesive properties of natural mussels and the redox electron pairs formed by catechol and metal ions. It has bionic electrical activity matching with the tissue and can conduct the electrical signal generated by the piezoelectric effect to the wound site so as to facilitate the electrical stimulation treatment of tissue repair. In addition, in vitro and in vivo experiments demonstrated that SEWD converts mechanical energy into electricity to stimulate cell proliferation and wound healing. The proposed healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.


Asunto(s)
Vendajes , Biomimética , Adhesivos , Cicatrización de Heridas , Hidrogeles/química
3.
Biomacromolecules ; 24(8): 3532-3544, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37417966

RESUMEN

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with ß-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.


Asunto(s)
Artritis Reumatoide , Curcumina , Humanos , Ácido Hialurónico/química , Preparaciones Farmacéuticas , Calidad de Vida , Curcumina/química , Artritis Reumatoide/tratamiento farmacológico , Péptidos , Portadores de Fármacos/química
4.
Biomacromolecules ; 23(10): 4357-4369, 2022 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-36166656

RESUMEN

In traditional blood-contacting medical devices, infection and thrombosis are easily formed on the surface of the materials. In addition, inflammation is also a clinical complication that cannot be ignored. More importantly, there is a mutually promoting relationship between the inflammatory response and the infection as well as thrombosis. In this work, we propose a self-adaptive anti-inflammatory coating strategy combined with anti-infection and anticoagulant capacity, which was accomplished based on nano-Ag particles and dexamethasone (Dex)-loaded hydrogel coating. The coating loaded with nano-Ag endows it with good bactericidal performance, including Gram-positive and Gram-negative bacteria. As an anti-inflammatory drug, Dex was grafted onto hydrogel coating by a reactive oxygen species (ROS)-cleavable thioketal (TK) bond and released upon the trigger of an inflammatory environment, blocking further inflammatory cascade, providing self-adaptive anti-inflammatory properties, and avoiding side effects of the drug. It was demonstrated that the coating worked as a precise strategy to resist coagulation, infection, and inflammation, provided a new perspective for designing clinical complication-conformable coatings, and had great application prospects on blood-contacting medical devices.


Asunto(s)
Antiinfecciosos , Trombosis , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Anticoagulantes , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Dexametasona/farmacología , Bacterias Gramnegativas , Bacterias Grampositivas , Humanos , Hidrogeles/farmacología , Inflamación/tratamiento farmacológico , Especies Reactivas de Oxígeno , Propiedades de Superficie
5.
Carcinogenesis ; 42(5): 724-732, 2021 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-33480980

RESUMEN

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.


Asunto(s)
Dieta Baja en Carbohidratos/efectos adversos , Carbohidratos de la Dieta/metabolismo , Neoplasias Pancreáticas/metabolismo , Anciano , Estudios de Cohortes , Grasas de la Dieta/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/patología , Factores de Riesgo , Pérdida de Peso/fisiología
6.
J Cell Mol Med ; 2021 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-33993634

RESUMEN

5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein, the regulatory effects of which have not been well characterized. This study aimed to investigate the expression profile and functional regulation of NT5DC2 and its potential interplay with TEAD4 in leiomyosarcoma (LMS). Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) program. LMS cell lines SK-LMS-1 and SK-UT-1 were used for both in vitro and in vivo analysis. Results showed that NT5DC2 is aberrantly upregulated in LMS. Its overexpression was associated with unfavourable survival. Deletion of NT5DC2 significantly reduced the expression of cyclin B1, cyclin A2, cyclin E1 and CDK1 and increased G1 phase arrest in LMS cell lines, and suppressed their proliferation both in vitro and in vivo. NT5DC2 interacted with unpalmitoylated TEAD4, and this association reduced TEAD4 degradation via the ubiquitin-proteasome pathway. TRIM27 is a novel E3 ubiquitin ligase that induces K27/48-linked ubiquitination of unpalmitoylated TEAD4 at Lys278. TEAD4 inhibition significantly suppressed LMS cell growth both in vitro and in vivo. Dual-luciferase assay demonstrated that TEAD4 could bind to the NT5DC2 promoter and activate its transcription. Based on these findings, we infer that the NT5DC2-TEAD4 positive feedback loop plays an important role in LMS development and might serve as a potential therapeutic target.

7.
Biomacromolecules ; 22(8): 3510-3521, 2021 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-34288655

RESUMEN

Hydrophobic acrylic intraocular lenses (IOLs) are widely used in cataract treatment for posterior capsule opacification (PCO) prophylaxis. However, undesired glistening and postoperative endophthalmitis are two major potential risks. Hence, a series of poly(2-phenoxyethyl methacrylate-co-2-phenoxyethyl acrylate-co-2-ethylhexyl methacrylate) (PPPE) acrylic IOL materials were synthesized for "glistening-free" optimization. The selected PPPE with 2% 2-ethylhexyl methacrylate showed excellent optical, foldable, and thermomechanical properties. The anterior surface of PPPE was coated with polydopamine followed by gentamycin conjugation (PDA/GS). It inhibited bacterial adhesion by 74% and decreased the biofilm thickness by 87%. In inflammatory mimicking conditions, bacterial proliferation was restrained, with acidic-dependent GS release behavior. The surface of PPPE toward the posterior capsule remained hydrophobic. It was conducive to human lens epithelial cell adhesion, collagen IV and fibronectin adsorption, and the following "sealed sandwich structure" formation. In summary, the PPPE with a dual-side heterogeneous surface displayed good application prospects in postoperative endophthalmitis and PCO prevention.


Asunto(s)
Opacificación Capsular , Endoftalmitis , Cápsula del Cristalino , Lentes Intraoculares , Materiales Biocompatibles , Endoftalmitis/prevención & control , Humanos , Complicaciones Posoperatorias/prevención & control , Diseño de Prótesis
8.
Biomacromolecules ; 22(2): 823-836, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33375781

RESUMEN

Heart valve replacement is an effective therapy for patients with moderate to severe valvular stenosis or regurgitation. Most bioprosthetic heart valves applied clinically are based on cross-linking with glutaraldehyde (GLUT), but they have some drawbacks like high cytotoxicity, severe calcification, and poor hemocompatibility. In this study, we focused on enhancing the properties of bioprosthetic heart valves by cross-linking with 3,4-dihydroxybenzaldehyde (DHBA). The experiment results revealed that compared with GLUT cross-linked porcine pericardium (PP), the relative amount of platelets absorbed on the surface of DHBA cross-linked PP decreased from 0.294 ± 0.034 to 0.176 ± 0.028, and the activated partial thromboplastin time (APTT) increased from 9.9 ± 0.1 to 15.2 ± 0.1 s, indicating improved hemocompatibility. Moreover, anticalcification performance and cytocompatibility were greatly enhanced by DHBA cross-linking. In conclusion, the properties of bioprosthetic valves could be effectively improved by processing valves with a DHBA-based cross-linking method.


Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Animales , Benzaldehídos , Catecoles , Reactivos de Enlaces Cruzados , Glutaral , Humanos , Pericardio , Porcinos
9.
Int J Hyperthermia ; 38(1): 1375-1383, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34541997

RESUMEN

PURPOSE: This study aimed to compare the survival benefits between high-intensity focused ultrasound (HIFU) combined with chemotherapy and chemotherapy alone in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). METHODS: All randomized clinical trials (RCTs) and observational studies were systematically searched through the databases of PubMed, EMBASE, CNKi and CQVIP up to December 2020. Case reports, case series and nonsystematic reviews were excluded. A meta-analysis was conducted to generate combined hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). RESULTS: Seven trials, containing a total of 992 patients, were included in this study. The meta-analysis showed that a combination of HIFU and chemotherapy increased overall survival compared with chemotherapy alone, with a pooled HR of 0.40 (95% confidence interval [CI], 0.28-0.58). The combined therapy group had a significant advantage in 1-year survival rate (OR: 0.35, 95% CI: 0.22-0.53, p = 0.00). The trial sequence analysis (TSA) showed that there were enough trials to control for random errors. CONCLUSION: Our analysis suggests that HIFU combined with chemotherapy intravenously will prolong survival for unresectable PDAC patients. The TSA showed that the survival benefit of combined therapy was definitive and there was no need to expand the sample size for repetitive exploration.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico
10.
Carcinogenesis ; 41(11): 1576-1582, 2020 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-32188964

RESUMEN

The difference of the patients bearing hepatocellular carcinoma (HCC) with and without cirrhosis at clinical level has not been completely determined. This study compared their differences in clinicopathological traits and prognostic factors for relapse-free survival (RFS) and overall survival (OS). Animal model was established to validate the result of clinical observation. As a result, 82 patients bearing HCC with no cirrhosis (HCC-NC) and 146 patients bearing HCC with cirrhosis (HCC-C) were included. HCC-NC exhibited shorter prothrombin time and higher plasma albumin than HCC-C. In HCC-NC, satellite nodule was an independent risk factor for OS, and high γ-glutamyl transpeptidase was an independent risk factor for RFS. In HCC-C, female sex was an independent risk factor for OS. Stratified analysis showed the OS and RFS of HCC-NC were better than HCC-C in conditions like without cancer embolus (in the portal vein or bile duct), without lymphadenopathy in hepatic portal, without satellite nodule and with small or high-differentiated tumor. Animal model analysis showed HCC-NC had a higher liver/body weight ratio, less tumor count and smaller max tumor volume than HCC-C. In conclusion, clinicopathological traits and risk factors influencing postoperative OS and RFS differed between patients with HCC-C and HCC-NC.


Asunto(s)
Carcinoma Hepatocelular/patología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Animales , Apoptosis , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Femenino , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Tasa de Supervivencia , Carga Tumoral , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
11.
J Cell Mol Med ; 24(1): 1010-1021, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31742892

RESUMEN

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA-Sarcoma (SARC), we explored relapse-related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2-gene signature. The 2-gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse-free survival (RFS) (HR: 2.966, 95%CI: 1.995-4.410 P < .001), and disease-specific survival (DSS) (HR: 2.283, 95%CI: 1.358-3.835, P = .002), as a continuous variable. Gene-level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < -0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2-gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High-level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2-gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future.


Asunto(s)
Biomarcadores de Tumor/genética , Fibroma/patología , Fibrosarcoma/patología , Cadenas alfa de Integrinas/genética , Proteínas del Tejido Nervioso/genética , Proteína Fosfatasa 2/genética , Sarcoma/patología , Estudios de Casos y Controles , Quimioradioterapia Adyuvante , Femenino , Fibroma/genética , Fibroma/terapia , Fibrosarcoma/genética , Fibrosarcoma/terapia , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Sarcoma/genética , Sarcoma/terapia , Tasa de Supervivencia
12.
Small ; 16(45): e2003253, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33078569

RESUMEN

Atherosclerosis, characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause cardiovascular diseases. Although conventional anti-inflammatory drugs reveal a certain amount of therapeutic effect, more reasonable design on plaque targeting, local anti-inflammation, and lipid removal are still required for comprehensive atherosclerosis therapy. In this work, a theranostic nanoplatform is developed for atherosclerosis recognition and inhibition. A two-photon aggregation-induced emission (AIE) active fluorophore (TP) developed is linked to ß-cyclodextrin (CD) with a ROS responsive bond, which can carry prednisolone (Pred) in its entocoele via supramolecular interaction to build a diagnosis-therapy compound two-photon fluorophore-cyclodextrin/prednisolone complexes (TPCDP). With TPCDP packaged by nanosized micelles based on a ROS sensitive copolymer poly (2-methylthio ethanol methacrylate)-poly (2-methacryloyloxyethyl phosphorylcholine), the TPCDP@PMM can accumulate in atherosclerotic tissue through the damaged vascular endothelium. Activated by the local overexpressed ROS and rich lipid, the micelles are interrupted and TPCDP is further disintegrated with Pred release due to the relatively stronger interaction of lipid with CD, resulting in anti-inflammatory activity and lipid removal for atherosclerosis inhibition. Besides, labeled with the TP, TPCDP@PMM indicates a distinct two-photon AIE imaging on atherosclerosis recognition. The "two-pronged" therapeutic effect and plaque location ability has been confirmed in vivo on ApoE-/- mice, holding TPCDP@PMM a great promise for atherosclerosis theranostics.


Asunto(s)
Aterosclerosis , Micelas , Animales , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Ratones , Polímeros/uso terapéutico , Especies Reactivas de Oxígeno
13.
J Cell Mol Med ; 23(11): 7673-7684, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31468674

RESUMEN

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.


Asunto(s)
Anexina A5/metabolismo , Quimiocina CXCL12/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Proteínas Recombinantes de Fusión/uso terapéutico , Administración Intravenosa , Animales , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quimiotaxis/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos C57BL , Infarto del Miocardio/patología , Isquemia Miocárdica/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Neovascularización Fisiológica/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Receptores de Quimiocina/metabolismo , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacología , Transducción de Señal/efectos de los fármacos
14.
Bioconjug Chem ; 30(7): 2075-2087, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31260272

RESUMEN

Intelligent polymeric micelles provide great potential for accurate cancer theranostics. Herein, gemcitabine (GEM)-conjugated redox-responsive prodrug micelles based on a pH-responsive charge-conventional PMPC-b-P (DEMA-co-SS-GEM-co-TPMA) copolymer and a two-photon absorbing aggregation-induced emission (AIE) fluorescence probe have been developed for lysosome-targeted drug release and bioimaging. The multifunctional copolymer has been synthesized via RAFT polymerization, and GEM is conjugated to the copolymer via GSH-cleavable disulfide bonds. These GEM-conjugated micelles exhibit great pH responsiveness at pH 5.0, while being stable at pH 6.0. GSH-triggered drug release can be observed with the GSH concentration increased from 0 to 10 mM. Moreover, the high-quality AIE-active two-photon imaging is confirmed by cell and deep-tissue imaging. More importantly, the distribution of these nanocarriers can be traced because of the AIE feature of the micelles. Along with good in vitro and in vivo tumor-suppression ability and significantly reduced side effects, this smart two-photon AIE micelle would be a potential candidate for cancer diagnosis and therapy.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/química , Desoxicitidina/análogos & derivados , Colorantes Fluorescentes/química , Polímeros/química , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Micelas , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Imagen Óptica , Gemcitabina
15.
Biomacromolecules ; 20(12): 4581-4592, 2019 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-31697486

RESUMEN

Recently, rapid acquisition of antibiotic resistance, increased prevalence of antibiotic-resistant bacterial infections, and slow healing of infected wound have led to vast difficulties in developing innovative antimicrobial agents to obliterate pathogenic bacteria and simultaneously accelerate wound healing. To effectively solve this problem, we designed light-responsive multifunctional nanoparticles with conjugation of quaternary ammonium chitosan and photosensitizer chlorin e6 (Ce6) to merge chemical and photodynamic therapy to efficient antibacteria. The Mg/(-)-epigallocatechin-3-gallate (EGCG) complex rapidly responded to light irradiation under 660 nm with release of magnesium ions, which effectively accelerated wound healing without toxicity to mammalian cells. Notably, positively charged nanoparticles could efficiently adhere to the bacterial surface, and reactive oxygen species (ROS) produced under laser irradiation destroyed the membrane structure of the bacteria, which is irreversible, ultimately leading to bacteria death. Thus, multifunctional nanoparticles with a combination of chemical and photodynamic antimicrobial therapy would offer guidance to rational predicted and designed new effective antimicrobial nanomaterials. Most importantly, it may represent a promising class of antimicrobial strategy for potential clinical translation.


Asunto(s)
Antiinfecciosos , Nanopartículas , Fotoquimioterapia , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/crecimiento & desarrollo , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Línea Celular , Clorofilidas , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Escherichia coli/crecimiento & desarrollo , Magnesio/química , Magnesio/farmacología , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Porfirinas/química , Porfirinas/farmacología , Ratas , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/patología , Infección de Heridas/metabolismo , Infección de Heridas/microbiología , Infección de Heridas/patología
16.
Xenotransplantation ; 26(2): e12481, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30609151

RESUMEN

BACKGROUND: Glutaraldehyde cross-linked bioprosthetic heart valves might fail due to progressive degradation and calcification. METHODS: In this study, we developed a new BHVs preparation strategy named as "HPA/TRA/FMN" that utilized 3,4-hydroxyphenylpropionic acid (HPA)/tyramine (TRA) conjugated pericardium and riboflavin 5'-monophosphate (FMN) initiated photo-cross-linking method. HPA/TRA-pericardium conjugation would provide extra phenol groups for FMN initiated photo-cross-linking. RESULTS: The feeding ratio of riboflavin 5'-monophosphate was optimized. The collagenase and elastase enzymatic degradation in vitro, biomechanics, calcification, elastin stability in vivo, and macrophage marker CD68 were characterized. We demonstrated that riboflavin photo-cross-linked pericardiums had great collagen and elastin stability, improved mechanical properties, better resistance for calcification, and less CD68 positive macrophages in rat subdermal implantation study. CONCLUSIONS: This new riboflavin photo-cross-linking strategy would be a promising method to make BHVs which have better elastin stability, less calcification, and reduced inflammatory response.


Asunto(s)
Calcinosis/inmunología , Reactivos de Enlaces Cruzados , Prótesis Valvulares Cardíacas , Riboflavina/inmunología , Animales , Bioprótesis , Glutaral/inmunología , Pericardio/inmunología , Trasplante Heterólogo/métodos
17.
J Mater Sci Mater Med ; 30(3): 38, 2019 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-30840150

RESUMEN

Glutaraldehyde (GLUT) crosslinked bioprosthetic heart valves (BHVs) might fail due to progressive degradation and calcification. GLUT cannot stabilize glycosaminoglycans (GAGs), which are important for BHVs' life time. In this current study we developed a new BHVs preparation strategy using exogenous hyaluronic acid (HA)/chondroitin sulfate (CS) supplement and sodium trimetaphosphate (STP) crosslinking method. Exogenous HA and CS provide additional GAGs for pericardiums. STP could link two GAGs by reacting with hydroxyl groups in GAGs' repeating polysaccharides units. The feeding ratios of HA/CS were optimized. The GAGs content and long-term stability in vitro, biocompatibility, the in vivo GAGs stability and anti-calcification potential of GLUT/HA/CS and STP treated pericardiums were characterized. We demonstrated that GLUT/HA/CS and STP treated pericardiums had sufficiently increased GAGs' amount and stability and decreased calcification. This new exogenous hyaluronic acid/chondroitin sulfate supplement and sodium trimetaphosphate crosslinking strategy would be a promising method to make BHVs with better structural stability and anti-calcification properties.


Asunto(s)
Bioprótesis , Sulfatos de Condroitina/química , Reactivos de Enlaces Cruzados/química , Glicosaminoglicanos/química , Prótesis Valvulares Cardíacas , Ácido Hialurónico/química , Animales , Válvula Aórtica/cirugía , Materiales Biocompatibles , Coagulación Sanguínea , Glutaral/química , Masculino , Pericardio/patología , Adhesividad Plaquetaria , Polifosfatos/química , Ratas , Ratas Sprague-Dawley , Espectrofotometría Infrarroja , Sulfatos , Porcinos
18.
BMC Surg ; 19(1): 128, 2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31488117

RESUMEN

BACKGROUND: The aim of the study was to develop a scoring system for the prediction of postoperative complications of open hepatectomy. METHOD: All consecutive patients receiving open hepatectomy from 2015 to 2017 were included in the study. Univariate and multivariate analyses were used to confirm the risk factors for postoperative complications. Afterwards, a novel scoring system was developed to predict the postoperative complications. RESULTS: The study included a total of 207 patients. For the test dataset, multivariate analysis indicated that diabetes, scale of surgery, serum potassium, and blood loss versus body weight were independent risk factors of the postoperative complications. The area under the curve (AUC) of the novel scoring system we proposed for prediction of postoperative complications of hepatectomy was 0.803, which is comparable with the AUCs of previous scoring systems. Furthermore, in the validation dataset, the corresponding AUC of the new scoring system was 0.717. CONCLUSION: This novel and simplified scoring system can effectively predict the postoperative complications of open hepatectomy and could help identify patients who are at high risk of postoperative complications.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(1): 164-171, 2019 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-30887792

RESUMEN

Marine-derived biopolymers are excellent raw materials for biomedical products due to their abundant resources, good biocompatibility, low cost and other unique functions. Marine-derived biomaterials become a major branch of biomedical industry and possess promising development prospects since the industry is in line with the trend of "green industry and low-carbon economy". Chitosan and alginates are the most commonly commercialized marine-derived biomaterials and have exhibited great potential in biomedical applications such as wound dressing, dental materials, antibacterial treatment, drug delivery and tissue engineering. This review focuses on the properties and applications of chitosan and alginates in biomedicine.

20.
Cell Physiol Biochem ; 48(4): 1443-1456, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30064138

RESUMEN

BACKGROUND/AIMS: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. METHODS: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. RESULTS: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients' clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients' tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients' age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients' postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. CONCLUSIONS: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.


Asunto(s)
Carcinoma Hepatocelular/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Biología Computacional , Supervivencia sin Enfermedad , Femenino , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , MicroARNs/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , alfa-Fetoproteínas/análisis
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