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1.
Acta Biochim Biophys Sin (Shanghai) ; 56(3): 405-413, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38425245

RESUMO

RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKß and IκBα are decreased. Moreover, the level of GSK3ß is increased, whereas the levels of Wnt3a, ß-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/ß-catenin signaling pathways in colonic cells.


Assuntos
Colite , NF-kappa B , Animais , Camundongos , beta Catenina/genética , beta Catenina/metabolismo , Colite/genética , Camundongos Knockout , NF-kappa B/metabolismo , Via de Sinalização Wnt
2.
Anal Chem ; 95(12): 5307-5315, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36930830

RESUMO

The rarity of circulating tumor cells (CTCs) and the complexity of blood components present major challenges for the efficient isolation of CTCs in blood. The coexisting matters could interfere with the detection of CTCs by adhering to the binding sites on the material surface, leading to the reduced accuracy of biomarker capture in blood. Herein, we developed dynamic bioactive lubricant-infused slippery surfaces by grafting the 1H,1H,2H,2H-heptadecafluorodecyl acrylate polymer and 3-acrylamidophenylboronic acid polymer brushes on quartz plates by UV light-initiated and then grafted cancer cell-binding peptides via reversible catechol-boronate chemistry between phenylboronic acid groups and 3,4-dihydroxy-l-phenylalanine groups of peptides for high-efficient capture of CTCs and nondestructive release of the desired cells in sugar response. Patterned dynamic bioactive lubricant-infused surfaces (PDBLISs) further exhibited the improved capture efficiency of CTCs and more effective antifouling properties for nonspecific cells and blood components. Moreover, the PDBLIS can efficiently capture rare cancer cells from the mimic of cancer patient's blood samples. We anticipate that the strategy we proposed would be used in further clinical diagnosis of complicated biofluids related to a variety of tumors and exhibit good prospects and potential in future liquid biopsies.


Assuntos
Células Neoplásicas Circulantes , Humanos , Separação Celular , Células Neoplásicas Circulantes/patologia , Células MCF-7 , Linhagem Celular Tumoral , Peptídeos
3.
Proc Natl Acad Sci U S A ; 117(28): 16127-16137, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601214

RESUMO

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.


Assuntos
Adesivos/química , Materiais Revestidos Biocompatíveis/química , Peptídeos/química , Stents , Adesivos/síntese química , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Química Click , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Miócitos de Músculo Liso/citologia , Óxido Nítrico/química , Compostos Organosselênicos/química , Peptídeos/síntese química , Proteínas/química , Coelhos , Stents/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle
4.
Langmuir ; 37(50): 14638-14645, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34879653

RESUMO

As mimics of the extracellular matrix, surfaces with the capability of capturing and releasing specific cells in a smart and controllable way play an important role in bacterial isolation. In this work, we fabricated a dual-responsive smart biointerface via peptide self-assembly and reversible covalent chemistry biomimetic adhesion behavior for bacterial isolation. Compared with that of the biointerface based on a single reversible covalent bond, the bacterial enrichment efficiency obtained in this work was 2.3 times higher. Furthermore, the release of bacteria from the surface could be achieved by dual responsiveness (sugar and enzyme), which makes the biointerface more adaptable and compatible under different conditions. Finally, the reusability of the biointerface was verified via peptide self-assembly and the regenerated smart biointerface still showed good bacterial capture stability and excellent release efficiency, which was highly anticipated to be more widely applied in biomaterial science and biomedicine in the future.


Assuntos
Adesivos , Biomimética , Bactérias , Materiais Biocompatíveis , Peptídeos
5.
Acc Chem Res ; 52(6): 1611-1622, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30793586

RESUMO

Dynamic synthetic biointerface is a new concept of biomaterials with smart surface properties capable of controlled display of bioactive ligands, dynamic modulation of cell-biomaterial interactions, and subsequently clever manipulation of fundamental cell behaviors like adhesion, migration, proliferation, differentiation, apoptosis, and so on. As mimics of the extracellular matrix (ECM), such molecularly dynamic biointerfaces have attracted increasing attention because of their tunable biological effects with great significance in in situ cell biology, tissue engineering, drug targeting, and cell isolation for cancer theranostics. Approaches to control bioligand presentation on materials mainly rely on surface functionalization with dynamic or reversible chemical linkers to which the ligands are tethered. Photoelectric-transformable or photocleavable chemistry, host-guest supramolecular chemistry, and multiple noncovalent interactions were initially employed for fabrication of dynamic synthetic biointerfaces. However, the external stimuli required in these systems, including electrochemical potential, electrochemical reaction, and near-infrared or UV light, are mostly invasive to living cells; and few of them are able to respond to the stimuli occurring in natural biological processes. In addition, most of current systems focused only on the control of cell adhesion, other cell behaviors like migration, differentiation and apoptosis have rarely been explored. Therefore, the development of novel synthetic biointerfaces that permit access to noninvasive control of diverse cell behaviors still represents a key challenge in biomaterials science. Our group pioneers the use of reversible covalent bonds, metal coordinative interactions, and the molecular affinity of molecularly imprinted synthetic receptors as the dynamic driving forces for the fabrication of smart biointerfaces. Several typical biological stimuli, such as glycemic volatility, body temperature fluctuations, regional disparity of pH values, and specific biomolecules, were tactfully involved in our systems. In this Account, we highlight the strategies we have used on the exploitation of dynamic synthetic biointerfaces based on the above three types of reversible chemical interactions. While our attention has been focused on biologically stimuli-responsive or other noninvasive ligand presentation, the versatility of dynamic synthetic biointerfaces in control of cell adhesion, directing cell differentiation, and targeting cell apoptosis has also been successfully demonstrated. In addition, a paradigm shift of dynamic synthetic biointerfaces from macroscopic to microscopic scale (e.g., nanobiointerfaces) was conceptually demonstrated in our research. The potential applications of these developed dynamic systems, including fundamental cell biology, surface engineering of biomaterials, scaffold-free tissue engineering, cell-based cancer diagnosis, and drug targeting cancer therapy, were also introduced, respectively. Although the development of dynamic synthetic biointerfaces is still in its infancy, we strongly believe that further efforts in this field will play a continuously and increasingly significant role in bridging the gap between chemistry and biology.


Assuntos
Materiais Biocompatíveis/farmacologia , Materiais Biomiméticos/farmacologia , Adesão Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Matriz Extracelular/química , Humanos , Ligantes , Propriedades de Superfície
6.
Med Sci Monit ; 24: 7035-7042, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30281585

RESUMO

BACKGROUND Colon cancer is one of the most common cancers and it is the fourth leading cause of cancer-related deaths worldwide. YAP can promote cell proliferation and inhibit apoptosis, leading to loss of cell contact inhibition and promoting malignant cell transformation. MATERIAL AND METHODS In this study we analyzed the effects of different curcumin concentrations on the proliferation of colon cancer cells using MTT and colony formation assays. Western blot detection was performed to confirm the YAP, LC3-II, and P62 expression. RESULTS Curcumin inhibited proliferation and promoted colon cancer cell autophagy. In addition, Western blot results indicated that curcumin suppressed YAP expression in colon cancer cells. To assess the mechanism, we treated the cell lines with curcumin and assessed YAP overexpression and YAP knockdown. The results revealed that curcumin inhibits the proliferation and promotes autophagy of these cell lines. Western blot results showed that curcumin reversed the effect of YAP in colon cancer cells. CONCLUSIONS Our results suggest that YAP has great promise for treatment of colon cancer and that it might be a potential diagnostic marker for colon cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Neoplasias do Colo/patologia , Curcumina/farmacologia , Fosfoproteínas/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Humanos , Fosfoproteínas/metabolismo , Fatores de Transcrição , Proteínas de Sinalização YAP
7.
Angew Chem Int Ed Engl ; 57(26): 7878-7882, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29733501

RESUMO

Reported here is a novel dynamic biointerface based on reversible catechol-boronate chemistry. Biomimetically designed peptides with a catechol-containing sequence and a cell-binding sequence at each end were initially obtained. The mussel-inspired peptides were then reversibly bound to a phenylboronic acid (PBA) containing polymer-grafted substrate through sugar-responsive catechol-boronate interactions. The resultant biointerface is thus capable of dynamic presentation of the bioactivity (i.e. the cell-binding sequence) by virtue of changing sugar concentrations in the system (similar to human glycemic volatility). In addition, the sugar-responsive biointerface enables not only dynamic modulation of stem cell adhesion behaviors but also selective isolation of tumor cells. Considering the highly biomimetic nature and biological stimuli-responsiveness, this mussel-inspired dynamic biointerface holds great promise in both fundamental cell biology research and advanced medical applications.


Assuntos
Bivalves/química , Separação Celular/métodos , Animais , Materiais Biocompatíveis/química , Biomimética , Ácidos Borônicos/química , Catecóis/química , Humanos , Células MCF-7 , Técnicas de Microbalança de Cristal de Quartzo
8.
Transgenic Res ; 23(2): 341-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24338332

RESUMO

Gender-preferential gene expression is a widespread phenomenon in humans. It is important to study how gender differences influence the pathogenesis of various diseases and response to specific drugs. The aim of this study is to determine if the mouse albumin enhancer/promoter may serve as the promoter to introduce gender-preferential gene expression in transgenic animals. We created four independent transgenic rat lines in which the human C-reactive protein transgene was under the control of mouse albumin enhancer/promoter. Quantitative real time RT-PCR analysis showed that transgene expression in the liver of male rats was significantly higher than transgene expression in the female rats (P < 0.05).There was a 5.3-fold (male/female) difference in line-519, and a 12.2-fold (male/female) difference in line-488. Enzyme-linked immunosorbent assay showed that the serum of male transgenic rats had a 13- to 679-fold difference at the protein level on transgene production compared with female transgenic rats. The male-to-female difference in gene expression was 10- to 17-fold in the liver of transgenic rats. Orchiectomy dramatically reduced protein production from the transgene in the liver. Testosterone administration into female rats did not increase the transgene expression, but estrogen administration into the male rats reduced transgene expression. This study provides a valuable tool for investigating the pathological roles of genes that are expressed in a gender-preferential manner in human disease.


Assuntos
Albuminas/genética , Proteína C-Reativa/metabolismo , Regulação da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Transgenes/genética , Animais , Animais Geneticamente Modificados , Western Blotting , Proteína C-Reativa/genética , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Estrogênios/administração & dosagem , Estrogênios/farmacologia , Feminino , Humanos , Injeções Subcutâneas , Fígado/metabolismo , Masculino , Camundongos , Orquiectomia , Ovariectomia , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais , Testosterona/administração & dosagem , Testosterona/farmacologia
9.
J Hazard Mater ; 468: 133793, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387181

RESUMO

Tea polyphenols (TPs), like green tea polyphenol (GTP) and black tea polyphenol (BTP), with phenolic hydroxyl structures, form coordination and hydrogen bonds, making them effective for bridging inorganic catalysts and membranes. Here, TPs were employed as interface agents for the preparation of TPs-modified needle-clustered NiCo-layered double hydroxide/graphene oxide membranes (NiCo-LDH-TPs/GO). The incorporation of porous guest material, NiCo-LDH-TPs, facilitated water channel expansion, enhancing membrane permeability and resulting in the development of high-performance, sustainable catalytic cleaning membranes. The introduction of TPs through coordination weakened the surface electronegativity of NiCo-LDH, promoting a uniform mixed dispersion with GO and facilitating membrane self-assembly. NiCo-LDH-GTP/GO-5 and NiCo-LDH-BTP/GO-5 membranes demonstrated permeances of 85.98 and 90.76 L m-2 h-1 bar-1, respectively, with rejections of 98.73% and 99.54% for methylene blue (MB). Notably, the NiCo-LDH-BTP/GO-5 membrane maintained a high rejection of 97.11% even after 18 cycles in the catalytic cleaning process. Furthermore, the modification of GTP and BTP enhanced MB degradation through PMS activation, resulting in a 0.33% and 0.35% increase in the reaction rate constants of NiCo-LDH, respectively, while reducing metal ion spillover. These findings highlighted the potential of TPs in enhancing the efficiency and sustainability of catalytic cleaning GO membranes for water purification and separation processes.

10.
Adv Mater ; 36(9): e2309046, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38011581

RESUMO

Developing a robust strategy for profiling heterogeneous circular tumor cells specifically, distinguishing the phenotypes of which in blood sample of cancer patient precisely, and releasing them sequentially, is significant for cancer management by liquid biopsy. Herein, a bio-inspired free-standing and flexible film composed of TiO2 nanotube and silk fibroin, fabricated with multiply dynamic bioactive surface (TSF/MDBS) by a simple and eco-friendly way including using polydopamine chemistry and dual dynamic covalent chemistry, is reported. The as-prepared TSF/MDBS binds specific peptides toward cells with epithelial biomarker and human epithelial growth factor receptor 2 (HER2) biomarker, and antifouling agents bovine serum albumin for obviating platelets and proteins adhering of blood, can capture heterogeneous CTCs with enhanced capability due to the cytocompatible soft film and exquisite surface design, and further release the captured cells as program, by specifically breaking down the covalent bonds in sequence via the action of adding biocompatible molecules fructose and glutathione. By applying the TSF/MDBS, it can be tailored into desired pieces for identifying CTCs with different phenotypes (HER2-high and HER2-low) from the unprocessed blood samples of breast cancer patients, and finally profiling these heterogeneous CTCs, to discriminate HER2 positive or negative of breast cancer patients in clinical applications.


Assuntos
Neoplasias da Mama , Fibroínas , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Plaquetas , Tipagem Molecular , Biomarcadores
11.
Exploration (Beijing) ; 2(1): 20210093, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37324582

RESUMO

The extracellular matrix (ECM) provides not only physical support for the tissue structural integrity, but also dynamic biochemical cues capable of regulating diverse cell behaviors and functions. Biomaterial surfaces with dynamic ligand presentation are capable of mimicking the dynamic biochemical cues of ECM, showing ECM-like functions to modulate cell behaviors. This review paper described an overview of present dynamic biomaterial interfaces by focusing on currently developed molecular strategies for dynamic ligand presentation. The paradigmatic examples for each strategy were separately discussed. In addition, the regulation of some typical cell behaviors on these dynamic biointerfaces including cell adhesion, macrophage polarization, and stem cell differentiation, and their potential applications in pathogenic cell isolation, single cell analysis, and tissue engineering are highlighted. We hope it would not only clarify a clear background of this field, but also inspire to exploit novel molecular strategies and more applications to match the increasing demand of manipulating complex cellular processes in biomedicine.

12.
Materials (Basel) ; 15(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36079271

RESUMO

Ni-Mn-Sn ferromagnetic shape memory alloys, which can be stimulated by an external magnetic field, exhibit a fast response and have aroused wide attention. However, the fixed and restricted working temperature range has become a challenge in practical application. Here, we introduced strain engineering, which is an effective strategy to dynamically tune the broad working temperature region of Ni-Co-Mn-Sn alloys. The influence of biaxial strain on the working temperature range of Ni-Co-Mn-Sn alloy was systematically investigated by the ab initio calculation. These calculation results show a wide working temperature range (200 K) in Ni14Co2Mn13Sn3 FSMAs can be achieved with a slight strain from 1.5% to -1.5%, and this wide working temperature range makes Ni14Co2Mn13Sn3 meet the application requirements for both low-temperature and high-temperature (151-356 K) simultaneously. Moreover, strain engineering is demonstrated to be an effective method of tuning martensitic transformation. The strain can enhance the stability of the Ni14Co2Mn13Sn3 martensitic phase. In addition, the effects of strain on the magnetic properties and the martensitic transformation are explained by the electronic structure in Ni14Co2Mn13Sn3 FSMAs.

13.
J Colloid Interface Sci ; 593: 142-151, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33744525

RESUMO

The scaffold materials with good mechanical and structural properties, controlled drug release performance, biocompatibility and biodegradability are important tenet in tissue engineering. In this work, the functional core-shell nanofibers with poly(ε-caprolactone) (PCL) as shell and silk fibroin heavy chain (H-fibroin) as core were constructed by emulsion electrospinning. The transmission electron microscopy confirmed that the nanofiber with core-shell structure were successfully prepared. The constructed nanofiber materials were characterized by the several characterization methods. The results showed that ethanol treatment could induce the formation of ß-sheet of H-fibroin in composite nanofibers, thus improving the mechanical properties of PCL/H-fibroin nanofiber scaffold. In addition, we evaluated the potential of PCL/H-fibroin nanofiber membrane as a biological scaffold. It was found that PCL/H-fibroin nanofiber scaffold was more conducive to cell adhesion and proliferation with the increment of H-fibroin. Finally, in vitro drug release presented that PCL/H-fibroin core-shell nanofibers could effectively reduce the prophase burst of drug molecules and show the sustained drug release. The PCL/H-fibroin nanofiber scaffolds constructed in this work have good mechanical properties, biocompatibility, and display good potential in biomedical applications, such as drug carriers, tissue engineering and wound dressings, etc.


Assuntos
Fibroínas , Nanofibras , Liberação Controlada de Fármacos , Poliésteres , Seda , Engenharia Tecidual , Alicerces Teciduais
14.
J Hazard Mater ; 419: 126398, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34175700

RESUMO

Simultaneous construction of porous and hollow adsorbent, especially from gas-in-water Pickering emulsion (PE) reactor, is vital for improving mass transfer kinetics and uptake amount. Inspired by the formation process of stalagmites in karst cave, amino and amidoxime bifunctionalized lotus root-type microsphere with porous surface (NH2@AO-PLRMS) is prepared by the silica nanoparticles (SPs)-stabilized CO2-in-water Pickering emulsion reactor and subsequent two-step grafting polymerization. The important roles of SPs acting as Pickering emulsifier, surface pore-forming agent, and adjusting internal lotus root structure are confirmed. Lotus root-type pores are dependent on the interface intensity and the permeability for compressed CO2 bubbles in PE droplets. Benefitting from the lotus root-type structure and abundant affinity sites, the maximum uranium adsorption capacity of NH2@AO-PLRMS is 1214.5 mg·g-1 at 298 k, and an ultrafast uptake process can be achieved in the first 30 min. Both thermodynamic and kinetic studies indicate a spontaneous, entropy increased, and exothermic chemisorption process, and the synergies of amidoxime and amino groups can enhance the adsorption selectivity. Remarkably, NH2@AO-PLRMS displays a high uranium adsorption capacity and desorption efficiency after seven cycles. These findings provide a way to obtain adsorbents with enhanced uranium extraction performance from gas-in-water PE reactor.


Assuntos
Urânio , Dióxido de Carbono , Emulsões , Cinética , Porosidade , Água
15.
Biomater Sci ; 9(17): 5785-5790, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34350905

RESUMO

Herein we reported a versatile dynamic biointerface based on pH-responsive peptide self-assembly and disassembly to capture the bacteria to avoid bacteria further infected tissue around that can release peptides from the surface in a slightly acidic environment to kill the bacteria with the specificity. The exposed biointerface still presented infection resistance.


Assuntos
Bactérias , Peptídeos , Concentração de Íons de Hidrogênio
16.
Bioact Mater ; 6(5): 1308-1317, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33251380

RESUMO

In this work, a sialic acid (SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells. The SA-imprinting process was performed at 37 °C using thermo-responsive functional monomer, thus generating switchable SA-recognition sites with potent SA binding at 37 °C and weak binding at a lower temperature (e.g., 25 °C). Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids, the SA-imprinted hydrogel layer could be used for selective cancer cell recognition. Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples. In addition, the captured cells could be non-invasively released by lowing the temperature. Considering the non-invasive processing mode, considerable capture efficiency, good cell selectivity, as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors, this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.

18.
Colloids Surf B Biointerfaces ; 192: 111051, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32344165

RESUMO

Amyloid protein misfolds, abnormally aggregates and accumulates into amyloid deposits which endanger tissue functions and are closely related to the pathogenesis of many diseases including Type 2 Diabetes Mellitus (T2DM). There are on-going efforts to find new methods or effective reagents to disassemble and eliminate the existing amyloid aggregates. Herein, we showed that a gold nanoparticle-modified quasi-2D nanomaterial, Au/g-C3N4, could efficiently degrade preformed amyloid aggregates. Furthermore, the scavenger experiment revealed this photodegradation effect was depended on the induced oxygen radicals, particularly hydroxyl radical. The new finding in this work could demonstrate that a gold nanoparticle-modified quasi-2D nanomaterial would have potential applications in the strategy design of the treatment of amyloid related diseases in future.

19.
Mol Med Rep ; 22(3): 1783-1792, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32705176

RESUMO

The aim of the present study was to explore whether the hypertrophy of H9C2 cardiomyocytes was induced by high glucose, to investigate whether the calcium channel inhibitor (Norvasc) could inhibit this process and to clarify the possible signaling pathways. The morphology of H9C2 cells was observed under an optical microscope, and the cell surface area was measured by Image Pro Plus 6.1 software. Furthermore, fluorescence spectrophotometry was used to detect intracellular calcium concentration ([Ca2+]i). ELISA was performed to detect calcineurin (CaN) activity; reverse transcription­quantitative PCR and western blotting were performed to detect the mRNA and protein expression levels of CaN Aß subunit (CnAß), nuclear factor of activated T cells 3 (NFAT3) and ß type myosin heavy chain (ß­MHC). Cell size was increased with the increase in glucose concentration of culture medium at 48 and 72 h, respectively, and decreased with the addition of Norvasc compared with those without Norvasc (P<0.05). There was no significant difference in cell size with the addition of Norvasc compared with cells cultured with 5 mM glucose (P>0.05). The average [Ca2+]i activity of single cells in the 48­ and 72­h culture groups treated with 50 mM glucose was significantly higher than cells treated with 5 mM glucose (P<0.05); and the fluorescent value of average [Ca2+]i activity of single cells was lower, following the addition of Norvasc than that without Norvasc (P<0.05). CaN activity in the 48­ and 72­h culture group treated with 50 mM glucose was markedly higher than that treated with 5 mM glucose, and the activity of CaN notably decreased with the addition of Norvasc compared with those without Norvasc. The mRNA and protein expression levels of CnAß, NFAT3 and ß­MHC in the 48­ and 72­h culture groups treated with 50 mM glucose were all significantly higher than those treated with 5 mM glucose (P<0.05). The mRNA and protein expression of CnAß, NFAT3 and ß­MHC cultured with 50 mM glucose were significantly decreased following the addition of Norvasc (P<0.05). Thus, the calcium channel inhibitor Norvasc may inhibit high glucose­induced hypertrophy of H9C2 cardiomyocytes by inhibiting the Ca2+­CaN­NFAT3 signaling pathway.


Assuntos
Anlodipino/farmacologia , Cardiotônicos/farmacologia , Glucose/efeitos adversos , Miócitos Cardíacos/citologia , Fatores de Transcrição NFATC/genética , Proteínas do Tecido Nervoso/genética , Animais , Calcineurina/genética , Calcineurina/metabolismo , Cálcio/metabolismo , Linhagem Celular , Meios de Cultura/química , Regulação da Expressão Gênica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Fatores de Transcrição NFATC/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Miosina não Muscular Tipo IIB/genética , Miosina não Muscular Tipo IIB/metabolismo , Ratos
20.
ACS Appl Bio Mater ; 3(6): 3648-3655, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35025235

RESUMO

Membrane-disrupting antimicrobial peptides continue to attract increasing attention due to their potential to combat multidrug-resistant bacteria. However, some limitations are found in the success of clinical setting-based antimicrobial peptide agents, for instance, the poor stability of antimicrobial peptides in vivo and their short-term activity. Self-assembled peptide materials can improve the stability of antimicrobial peptides, but the biosafety of peptide-based materials is the main concern, although they are considered to be biocompatible, because some peptide aggregates would possibly induce protein misfolding, which could be related to amyloid-related diseases. Therefore, in this work, we designed two peptides and constructed peptide-based nanofibrils by self-assembly before its utilization. It is found that the fibrils could release the antimicrobial peptide by disassembly for microbial membrane lysis in the presence of bacteria. The designed peptide-based fibrils presented a good and long-term antimicrobial activity with bacterial membrane disruption and the efflux of calcium from bacteria. Furthermore, it could be used to construct hybrid macrofilms displaying low cytotoxicity, low hemolytic activity, and good biocompatibility. The innovative design strategy could be beneficial for the development of smart antimicrobial nanomaterials.

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