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1.
J Am Chem Soc ; 146(22): 15053-15060, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38776531

RESUMEN

Electrocatalysis is considered promising in renewable energy conversion and storage, yet numerous efforts rely on catalyst design to advance catalytic activity. Herein, a hydrodynamic single-particle electrocatalysis methodology is developed by integrating collision electrochemistry and microfluidics to improve the activity of an electrocatalysis system. As a proof-of-concept, hydrogen evolution reaction (HER) is electrocatalyzed by individual palladium nanoparticles (Pd NPs), with the development of microchannel-based ultramicroelectrodes. The controlled laminar flow enables the precise delivery of Pd NPs to the electrode-electrolyte interface one by one. Compared to the diffusion condition, hydrodynamic collision improves the number of active sites on a given electrode by 2 orders of magnitude. Furthermore, forced convection enables the enhancement of proton mass transport, thereby increasing the electrocatalytic activity of each single Pd NP. It turns out that the improvement in mass transport increases the reaction rate of HER at individual Pd NPs, thus a phase transition without requiring a high overpotential. This study provides new avenues for enhancing electrocatalytic activity by altering operating conditions, beyond material design limitations.

2.
Mol Cancer ; 23(1): 33, 2024 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355583

RESUMEN

BACKGROUND: Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. METHODS: In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting. RESULTS: The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway. CONCLUSION: Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC.


Asunto(s)
MicroARNs , Factores de Transcripción , Neoplasias de la Mama Triple Negativas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Endógeno Competitivo , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Circular/genética , Hibridación Fluorescente in Situ , Línea Celular Tumoral , Integrinas/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proteínas de Unión al ADN/metabolismo
3.
Small ; 20(16): e2306721, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38018340

RESUMEN

The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , MicroARNs , Humanos , Osteogénesis/genética , Exosomas/metabolismo , Hidrogeles , Angiogénesis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neovascularización Fisiológica , Regeneración Ósea , MicroARNs/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo
4.
J Org Chem ; 89(14): 9958-9971, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38981120

RESUMEN

Herein, a versatile highly regioselective three-component annulation of simple aromatic ketones and methylamines using a hypervalent iodine reagent for polyarylated 1-pyrrolines has been described in good to excellent yields. Meanwhile, unsymmetrical 1-pyrroline isomers could be realized and synthesized. Such an intriguing one-pot two-step tandem assembly strategy with green conditions and high regioselectivity shows predictable inspiration in related annulation reactions.

5.
Environ Res ; 252(Pt 4): 119074, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38705449

RESUMEN

China's carbon emission trading policy plays a crucial role in achieving both its "3060" dual carbon objectives and the United Nations Sustainable Development Goal 13 (SDG 13) on climate action. The policy's effectiveness in reducing pollution and mitigating carbon emissions holds significant importance. This paper investigated whether China's carbon emission trading policy affects pollution reduction (PM2.5 and SO2) and carbon mitigation (CO2) in pilot regions, using panel data from 30 provinces and municipalities in China from 2005 to 2019 and employing a multi-period difference-in-differences (DID) model. Furthermore, it analyzed the heterogeneity of carbon market mechanisms and regional variations. Finally, it examined the governance pathways for pollution reduction and carbon mitigation from a holistic perspective. The results indicate that: (1) China's carbon emission trading policy has reduced CO2 emissions by 18% and SO2 emissions by 36% in pilot areas, with an immediate impact on the "carbon mitigation" effect, while the "pollution reduction" effect exhibits a time lag. (2) Higher carbon trading prices lead to stronger "carbon mitigation" effect, and larger carbon market scales are associated with greater "pollution reduction" effects on PM2.5. Governance effects on pollution reduction and carbon mitigation vary among pilot regions: Carbon markets of Beijing, Chongqing, Shanghai, and Tianjin show significant governance effects in both "pollution reduction" and "carbon mitigation", whereas Guangdong's carbon market exhibits only a "pollution reduction" effect, and Hubei's carbon market demonstrates only a "carbon mitigation" effect. (3) Currently, China's carbon emission trading policy achieves pollution reduction and carbon mitigation through "process management" and "end-of-pipe treatment". This study could provide empirical insights and policy implications for pollution reduction and carbon mitigation, as well as for the development of China's carbon emission trading market.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Política Ambiental , China , Contaminación del Aire/prevención & control , Contaminación del Aire/legislación & jurisprudencia , Contaminación del Aire/análisis , Política Ambiental/legislación & jurisprudencia , Contaminantes Atmosféricos/análisis , Carbono/análisis , Dióxido de Carbono/análisis , Material Particulado/análisis
6.
Small ; 19(40): e2302346, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37287364

RESUMEN

Driven by the information industry, advanced electronic devices require dielectric materials which combine both excellent energy storage properties and high temperature stability. These requirements hold the most promise for ceramic capacitors. Among these, the modulated Bi0.5 Na0.5 TiO3 (BNT)-based ceramics can demonstrate favorable energy storage properties with antiferroelectric-like properties, simultaneously, attaching superior temperature stability resulted from the high Curie temperature. Inspired by the above properties, a strategy is proposed to modulate antiferroelectric-like properties via introducing Ca0.7 La0.2 TiO3 (CLT) into Bi0.395 Na0.325 Sr0.245 TiO3 (BNST) ((1-x)BNST-xCLT, x = 0.10, 0.15, 0.20, 0.25). Combining both orthorhombic phase and defect dipole designs successfully achieve antiferroelectric-like properties in BNST-CLT ceramics. The results illustrate that 0.8BNST-0.2CLT presents superior recoverable energy storage density ≈8.3 J cm-3 with the ideal η ≈ 80% at 660 kV cm-1 . Structural characterizations demonstrate that there is the intermediate modulated phase with the coexistence of the antiferroelectric and ferroelectric phases. In addition, in situ temperature measurements prove that BNST-CLT ceramics exhibit favorable temperature stability over a wide temperature range. The present work illustrates that BNT-based ceramics with antiferroelectric-like properties can effectively enhance the energy storage performance, which provides novel perspectives for the subsequent development of advanced pulsed capacitors.

7.
Int J Mol Sci ; 24(17)2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37686444

RESUMEN

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.


Asunto(s)
Cicatriz , Hidrogeles , Animales , Ratones , Ligandos , Huesos/diagnóstico por imagen , Tendones
8.
Small ; 18(6): e2104820, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34854551

RESUMEN

The field of living materials seeks to harness living cells as microfactories that can construct a material itself or enhance the performance of material in some manner. While recent advances in 3D printing allow microbe manipulation to create bespoke living materials, the effective coupling of these living components in reinforced bioink designs remains a major challenge due to the difficulty in building a robust and cell-friendly microenvironment. Here, a type of dual-network bioink is reported for the 3D printing of living materials with enhanced biocatalysis capabilities, where bioinks are readily printable and provide a biocompatible environment along with desirable mechanical performance. It is demonstrated that integrating microbes into these bioinks enables the direct printing of catalytically living materials with high cell viability and maintains metabolic activity, which those living materials can be preserved and reused. Further, a bacteria-algae coculture system is fabricated for the bioremediation of chemicals, giving rise to its potential field applications.


Asunto(s)
Bioimpresión , Biocatálisis , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido
9.
Anal Biochem ; 659: 114936, 2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36220375

RESUMEN

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a critical role in inflammatory and immunometabolism programming through catalyzing the oxidation of tryptophan (Trp) into downstream N-formylkynurenine. IDO1 is typically up-regulated in malignant tumors, making it a potential biomarker for cancer diagnosis. Here we show an effective strategy for tumor cell detection by integrating IDO1 activity assay with single cell-encapsulated droplets on a microfluidic platform for high-throughput bioanalysis. Mixed cells, as well as other cofactors, are encapsulated in individual droplets, which act as dynamic microreactors for IDO1-catalyzed oxidation of Trp. After pico-injection of a biosensing ensemble consisting of the macrocycle cucurbit [8]uril (Q8) and a fluorescent guest, rapid and robust screening of tumor cells by fluorescence signal is achieved in a few minutes reporting to Trp depletion, expanding the scope of conventional antibody-based detection of protein biomarkers. The results represent the first example of quantifying IDO1 enzymatic activity at the single cell level with a high-throughput performance, therefore promising warning signs and early diagnosis of tumor cells.


Asunto(s)
Neoplasias , Triptófano , Humanos , Triptófano/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/análisis , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Triptófano Oxigenasa , Neoplasias/diagnóstico , Oxidación-Reducción , Quinurenina/metabolismo
10.
Mol Pharm ; 19(11): 4149-4156, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36198565

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is closely related to tumor formation. We developed the radiolabeled peptide pair 68Ga/177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated DX600 (68Ga/177Lu-HZ20), for the targeting and mapping of ACE2-overexpressing tumors. 68Ga/177Lu-HZ20 was prepared with a routine labeling method. HepG2ACE2+/HepG2WT cell lines were used to evaluate the specificity of 68Ga/177Lu-HZ20. Pharmacokinetics, biodistribution, and micro-PET/CT and -SPECT/CT imaging were performed, and radiation dosimetry was estimated. Immunohistochemistry (IHC) staining was performed to assess the expression of ACE2 in tumors. The radiolabeling yields of 68Ga/177Lu-HZ20 were 88.49 ± 8.57% (n > 10) and 84.71 ± 9.75% (n > 10), with specific activities of (18.74 ± 3.72) × 106 and (17.85 ± 1.62) × 106 GBq/mol, respectively. 68Ga/177Lu-HZ20 showed significant differences in the cellular uptake of HepG2ACE2+/HepG2WT cells and fast clearance in KM mice. Moreover, HepG2ACE2+ tumors were clearly visualized in 68Ga/177Lu-HZ20 micro-PET/SPECT images. Based on micro-PET/CT, the standard uptake value (SUVmax) of HepG2ACE2+ tumors was 0.66 ± 0.02 at 30 min postinjection, IHC confirmed the high expression of ACE2 in HepG2ACE2+ tumors. In PET/CT images, the SUVmean of volunteer 1 was higher than the 18F-FDG value in the same lesion. 68Ga/177Lu-HZ20 was successfully obtained and showed high and specific uptake in tumors overexpressing ACE2. They may serve as paired probes for ACE2-targeting theranostics.


Asunto(s)
Radioisótopos de Galio , Neoplasias , Animales , Ratones , Enzima Convertidora de Angiotensina 2 , Línea Celular Tumoral , Péptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único
11.
Aesthetic Plast Surg ; 46(6): 2655-2664, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35237883

RESUMEN

BACKGROUND: Gynecomastia (GYN) is the most common benign disease in males. A vacuum-assisted biopsy is a minimally invasive surgical technique for GYN treatment that achieves satisfactory aesthetic results. However, due to the operation under non-direct vision, it is difficult to localize the bleeding points and assess the residual glandular tissue. Endoscopy was applied to observe the operative field after subcutaneous mastectomy. The present study aimed to recommend our initial experience in glandular GYN with endoscope-assisted minimally invasive subcutaneous mastectomy. METHODS: A total of 34 patients diagnosed with glandular GYN (50 breasts), treated with endoscope-assisted minimally invasive surgery at The First Affiliated Hospital with Nanjing Medical University between June 2018 and June 2020, were enrolled in this study. According to Simon's classification of the breast, 10 was grade I, 25 was grade IIA, and 15 was grade IIB. The characteristics of patients, operative data, postoperative complications, cosmetic outcome, and patient satisfaction were recorded. RESULTS: Endoscope-assisted minimally invasive mastectomy was performed successfully in all cases. The operative duration of the operation was 55-120 min/side. The total weight of the resected tissue of the 50 breasts was 55-350 g, and the blood loss was 10-105 mL/breast. Endoscopy detected five breasts with bleeding and three with residual glandular during the operation. Postoperative bleeding occurred in 1 breast, subcutaneous seroma in 3 breasts, dysesthesia of the nipple-areolar complex in 2 breasts, and skin redundancy in a bilateral patient. None of the patients experienced severe pain, infection, nipple necrosis, and nipple retraction, a saucer-like deformity. With a median follow-up of 21 months, all patients were satisfied with their cosmetic outcome (100%), and no recurrence occurred. CONCLUSION: Endoscope-assisted minimally invasive mastectomy could be used as a feasible technique for the treatment of glandular GYN. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online. Instructions to Authors www.springer.com/00266 .


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Mastectomía , Procedimientos Quirúrgicos Mínimamente Invasivos
12.
Angew Chem Int Ed Engl ; 61(34): e202206339, 2022 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-35735050

RESUMEN

While structural coloration has captured considerable interests across different areas in the past decades, the development of macroscopic objects with tailorable structural colors remains a challenge due to the difficulty of large-scale fabrication of finely ordered nanostructures and poor processability of their constituent materials. In this work, a type of photonic granular hydrogel is developed as a novel printable ink for constructing customized structural colored objects. The magnetochromatic ink exhibits dynamic properties such as shear thinning and self-healing, enabling direct writing of macroscopic structural colored patterns by extrusion 3D printing. Further, the modularity of the photonic ink allows additive color mixing, which obviates the need for arduous nano-synthesis and expands on the color abundance of structural colored materials in a simple yet efficient manner. These characteristics grant novel photonic inks with great applicability to a variety of fields including switchable color displays, sensors, etc.

13.
Small ; 17(8): e2007426, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33480481

RESUMEN

Despite the vast variety of colloidal superstructures available in soft matter photonics, it remains challenging to balance the trade-off between their optical microstructures and material processability. By synergizing colloidal photonics and dynamic chemistry, a type of photonic "plasticine" with characteristics of uniform structural colors, high processability, and self-healing is demonstrated. Specifically, a boronate ester bond-based macromonomer is first prepared through complexation between the diols of polyvinyl alcohol and the boronic acid group of 3-(acrylamido) phenylboronic acid in the presence of concentrated silica colloids. Upon photopolymerization, the dynamic photonic plasticine is formed in situ as the result of the crosslinking of the boronate ester bonded networks. The randomly packed colloids inside the plasticine compose the amorphous photonic crystals, giving rise to angle-independent structural colors that would not compromise during subsequent processing steps; the reversible nature of the boronate ester bonds endows the plasticine with self-adaptable and self-healing properties. Further, the plasticine is also compatible with common shaping methods, that is, cutting, molding, and carving, and thus can be facilely processed into 3D structural colored objects, holding great potentials in fields such as bio-encoding, optical filters, anti-counterfeiting, etc.

14.
Trends Analyt Chem ; 143: 116333, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34720276

RESUMEN

Infectious diseases caused by pathogenic microbes have posed a major health issue for the public, such as the ongoing COVID-19 global pandemic. In recent years, wastewater-based epidemiology (WBE) is emerging as an effective and unbiased method for monitoring public health. Despite its increasing importance, the advancement of WBE requires more competent and streamlined analytical platforms. Herein we discuss the interactions between WBE and droplet microfluidics, focusing on the analysis of pathogens in droplets, which is hard to be tackled by traditional analytical tools. We highlight research works from three aspects, namely, quantitation of pathogen biomarkers in droplets, single-cell analysis in droplets, and living cell biosensors in droplets, as well as providing future perspectives on the synergy between WBE and droplet microfluidics.

15.
Angew Chem Int Ed Engl ; 60(18): 10366-10374, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33594767

RESUMEN

We develop hetero-nanostructured black phosphorus/metal-organic framework hybrids formed by P-O-Co covalent bonding based on a designed droplet microfluidic strategy consisting of confined and ultrafast microdroplet reactions. The resulting hybrid exhibits large capacitance (1347 F g-1 ) in KOH electrolytes due to its large specific-surface-area (632.47 m2 g-1 ), well-developed micro-porosity (0.38 cm3 g-1 ), and engineered electroactivity. Furthermore, the proposed 3D printing method allows to construct all-integrated solid-state supercapacitor, which maintains interconnected porous network, good interfacial adhesion, and robust flexibility for short-path diffusion and excessive accommodation of ions. Consequently, the fabricated flexible supercapacitor delivers ultrahigh volumetric energy density of 109.8 mWh cm-3 , large capacitance of 506 F cm-3 , and good long-term stability of 12000 cycles.

16.
Exp Mol Pathol ; 114: 104416, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32165091

RESUMEN

Mesenchymal stromal injection is a promising therapy for traumatic brain injury (TBI). The aim of this study was to explore the effects of the HIF-1α/SDF-1/CXCR4 axis on neuron repair in TBI rats through improving the bone marrow-derived mesenchymalstromal cells (BMSCs) migration. TBI rat models were established. The rats were treated with exogenous SDF-1, and then the neuronal apoptosis in TBI rats was measured. BMSCs from rats were collected, and the roles of NF-κB p65 expression in nuclei, overexpression of SDF-1 and HIF-1α, as well as downregulation of CXCR4 in BMSC migration were identified. HIF-1α- and SDF-1- treated BMSCs were transplanted into TBI rats, after which the neuronal apoptosis and activity of the HIF-1α/SDF-1/CXCR4 axis were detected. Consequently, we found SDF-1 elevated the HIF-1α/SDF-1/CXCR4 activity and presented protective roles in TBI rat hippocampal neurons with reduced neuronal apoptosis. SDF-1 promoted BMSC migration in vitro, and co-effects of SDF-1 and HIF-1α showed strong promotion, while CXCR4 inhibition suppressed BMSC migration. BMSC transplantation activated the HIF-1α/SDF-1/CXCR4 axis and reduced neuronal apoptosis in TBI rats. To conclude, our study demonstrated that the HIF-1α/SDF-1/CXCR4 axis could enhance BMSC migration and alleviate neuronal damage and apoptosis in TBI rats. This study provided novel options for TBI therapy.


Asunto(s)
Lesiones Traumáticas del Encéfalo/genética , Quimiocina CXCL12/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Receptores CXCR4/genética , Animales , Apoptosis/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Movimiento Celular/genética , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , Transducción de Señal/genética , Células del Estroma/metabolismo , Células del Estroma/patología
17.
Proc Natl Acad Sci U S A ; 114(31): 8163-8168, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28696304

RESUMEN

Inspired by biological systems, we report a supramolecular polymer-colloidal hydrogel (SPCH) composed of 98 wt % water that can be readily drawn into uniform ([Formula: see text]6-[Formula: see text]m thick) "supramolecular fibers" at room temperature. Functionalized polymer-grafted silica nanoparticles, a semicrystalline hydroxyethyl cellulose derivative, and cucurbit[8]uril undergo aqueous self-assembly at multiple length scales to form the SPCH facilitated by host-guest interactions at the molecular level and nanofibril formation at colloidal-length scale. The fibers exhibit a unique combination of stiffness and high damping capacity (60-70%), the latter exceeding that of even biological silks and cellulose-based viscose rayon. The remarkable damping performance of the hierarchically structured fibers is proposed to arise from the complex combination and interactions of "hard" and "soft" phases within the SPCH and its constituents. SPCH represents a class of hybrid supramolecular composites, opening a window into fiber technology through low-energy manufacturing.

18.
Angew Chem Int Ed Engl ; 59(17): 6902-6908, 2020 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-32017352

RESUMEN

Despite the importance of spatially resolved self-assembly for molecular machines, the spatial control of supramolecular polymerization with synthetic monomers had not been experimentally established. Now, a microfluidic-regulated tandem process of supramolecular polymerization and droplet encapsulation is used to control the position of self-assembled microfibrillar bundles of cyclic peptide nanotubes in water droplets. This method allows the precise preferential localization of fibers either at the interface or into the core of the droplets. UV absorbance, circular dichroism and fluorescence microscopy indicated that the microfluidic control of the stimuli (changes in pH or ionic strength) can be employed to adjust the packing degree and the spatial position of microfibrillar bundles of cyclic peptide nanotubes. Additionally, this spatially organized supramolecular polymerization of peptide nanotubes was applied in the assembly of highly ordered two-dimensional droplet networks.

19.
Anal Chem ; 91(23): 14943-14950, 2019 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-31714063

RESUMEN

We show how the macrocyclic host cucurbit[8]uril (CB[8]) and a fluorescent dye form a biosensing ensemble while its cavity simultaneously traps tryptophan, the upstream substrate of IDO1 enzymes, therefore providing a label-free method to monitor the activity of IDO1 in real time. Incubation of malignant HeLa and HepG2 cells overexpressing IDO1 with the associative biosensor resulted in its spontaneous uptake and a fluorescence switch-on response in situ, which can be traced to the displacement of tryptophan from CB[8] upon IDO1-catalyzed oxidation. The results, for the first time, establish a supramolecular sensing concept for the detection of intracellular enzymatic activity in live cells, thus allowing direct cell-based analysis and inhibitor screening compatible with commercial instruments including microplate reader, fluorescent microscopy, and flow cytometry.


Asunto(s)
Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Indolamina-Pirrol 2,3,-Dioxigenasa/análisis , Técnicas Biosensibles/instrumentación , Hidrocarburos Aromáticos con Puentes/química , Línea Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Imidazoles/química , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Oxidación-Reducción , Triptófano/química
20.
Cancer Sci ; 109(5): 1648-1659, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29575318

RESUMEN

Oncogene c-Src has been found to be a potential target for the treatment of triple-negative breast cancer (TNBC). However, the therapeutic effects of the c-Src inhibitor on TNBC patients are controversial compared to those on cell lines. The molecular mechanisms of the inhibitory effects of the c-Src inhibitor on TNBC remain unclear. Herein, we showed that a specific c-Src inhibitor, PP2, was effective in inhibiting phosphorylation of c-Src in 4 cell lines: T-47D, SK-BR-3, SUM1315MO2, and MDA-MB-231, regardless of hormone receptors and human epidermal growth factor receptor 2 (HER2) expression levels. Giving PP2 preferentially reduced the S phase of cell cycles and inhibited colony formation in SUM1315MO2 and MDA-MB-231, but not in SK-BR-3 and T-47D cells. Furthermore, PP2 effectively blocked cell migration/invasion and epithelial-mesenchymal transition (EMT) in TNBC cell lines, SUM1315MO2 and MDA-MB-231. An EMT biomarker, vimentin, was highly expressed in 2 TNBC cell lines when they were compared with SK-BR-3 and T-47D cells. Further depletion of vimentin by shRNA remarkably attenuated the inhibitory effects of the c-Src inhibitor on TNBC cells in vitro and in vivo, indicating a crucial action of vimentin to affect the function of c-Src in TNBC. This study provides an important rationale for the clinic to precisely select TNBC patients who would benefit from c-Src inhibitor treatment. This finding suggests that traditional markers for TNBC are not sufficient to precisely define this aggressive type of cancer. Vimentin is identified as an important biomarker to enable categorization of TNBC.


Asunto(s)
Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Vimentina/análisis , Familia-src Quinasas/antagonistas & inhibidores , Animales , Proteína Tirosina Quinasa CSK , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Fosforilación , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/metabolismo
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