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1.
Anal Methods ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924033

RESUMO

Alpha fetal protein (AFP) is a significant biomarker of liver cancer. Herein we developed a novel phage-mediated double-nanobody sandwich immunoassay (P-ELISA) for sensitive detection of AFP in serum, where the phage displayed the nanobody for antigen recognition and multiple copies of major coat protein pVIII for signal amplification. The expressed nanobody Nb-A1 and the phage-displayed nanobody phage-A2 served as the capture antibody and detection antibody, respectively. Based on the optimal experimental conditions, the P-ELISA has a half maximal saturation concentration of 24.85 ng mL-1 and a limit of detection of 0.237 ng mL-1 for AFP. The P-ELISA is highly selective for AFP and ignorable cross-reactions were observed with other tested cancer biomarkers. After elimination of the matrix effect by 30-fold dilution with 0.5 × PBS, clinical serum samples were analyzed by the P-ELISA. The results correlated well with those of the AFP commercial ELISA kit and the Roche E601 automatic chemiluminescence analyzer. Thus, it showed the potential of the recombinant phage for highly sensitive and selective detection of AFP and provides a novel detection model for the other disease-related biomarkers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32979083

RESUMO

Properly disposing of unused pharmaceuticals is essential to minimize emissions of active pharmaceutical ingredients (APIs). The aim of this study was to determine whether disposing of unused pharmaceuticals in household solid waste is a cost-effective way of attenuating pharmaceutical emissions. We calculated attenuation rates (ARs) for unused pharmaceuticals by performing mass balance calculations for disposal to landfill. The results indicated that the average ARs for disposal as household solid waste reached 63% to 100% for our investigated pharmaceuticals at the worst scenario, indicating that disposal as household solid waste strongly attenuated emissions of APIs. Disposing of unused pharmaceuticals as household solid waste could be a cost-effective disposal method from the view of reducing APIs emission, but should be used with caution.

3.
Sci Total Environ ; 746: 141405, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771764

RESUMO

In this study, we collected 308 serum samples from 17 to 20 year old first-year university students who were recruited from Lanzhou University in China a few days after their enrollment to measure the serum Pb, Cd, Hg, and As levels, and specific questionnaires for age, sex, settlement and dietary structure were designed. A 3-D atmospheric transport model was used to simulate the atmospheric concentration and dry deposition across China based on gridded Pb emission inventory to examine the association between the spatial distribution of serum concentrations and environmental fates of Pb. The mean serum Pb, Cd, Hg, and As concentrations averaged over all participating young students were 21.38, 1.46, 3.86, and 4.69 µg/L, respectively. The Pb, Cd, and Hg levels in 3%, 7%, and 20% serum samples exceeded the standards. The minimum serum As and Hg concentrations and the maximum serum Pb and Cd concentrations occurred in urban areas. Seafood diet habits (P < 0.05), sex (P < 0.05), and relocation (P < 0.01) caused significant differences in serum As, Pb, and Cd concentrations. A cluster analysis was carried out to classify the exposure pathways for target contaminants. The results indicated that 4 heavy metals in the serum of volunteers from northern China could be grouped into the same category, in which significant positive correlations were found between the serum heavy metal levels and background concentrations of surface soil. However, in other provinces and metropolises, the atmospheric pollution level played a critical role involving in the inhalation exposure pathway. We demonstrated that serum Pb levels in freshman students were related to the atmospheric transport and dry deposition of Pb.

4.
ACS Nano ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32432458

RESUMO

Among various energy storage devices, aqueous zinc-ion batteries (ZIBs) have captured great attention due to their high safety and low cost. One of the most promising cathodes of aqueous ZIBs is layered vanadium-based compounds. However, they often suffer from the capacity decaying during cycling. Herein, we prepared KV3O8·0.75H2O (KVO) and further incorporated it into a single-walled carbon nanotube (SWCNT) network, achieving freestanding KVO/SWCNT composite films. The KVO/SWCNT cathodes exhibit a Zn2+/H+ insertion/extraction mechanism, resulting in fast kinetics of ion transfer. In addition, the KVO/SWCNT composite films possess a segregated network structure, which offers the fast kinetics of electron transfer and guarantees an intimate contact between KVO and SWCNTs during cycling. As a result, the resultant batteries deliver a high capacity of 379 mAh g-1, excellent rate capability, and an ultralong cycle life up to 10,000 cycles with a high capacity retention of 91%. In addition, owing to the high conductivity and flexibility of KVO/SWCNT films, flexible soft-packaged ZIBs based on KVO/SWCNT film cathodes were assembled and displayed stable electrochemical performance at different bending states.

5.
Small ; : e1907153, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32285595

RESUMO

Lithium-sulfur (Li-S) batteries as a promising energy storage candidate have attracted attention due to their high energy density (2600 Wh kg-1 ). However, the serious shuttle effect caused by the dissolution of the lithium polysulfides (LiPS) in electrolyte significantly degrades their cycling life and rate performance. Herein, the "binary active sites" concept in a Li-S battery system via the design of a cobalt vanadium oxide (CVO) modified multifunctional separator is designed. In the case of CVO, active vanadium sites simultaneously anchor the LiPS through the chemical affinity and active cobalt sites can dominate a rapid kinetic conversion. Such a synergistic effect contributes to improving the utilization of sulfur in the electrochemical process for the enhanced electrochemical performance. As a result, the Li-S battery with the CVO modified separator possesses a high reversible capacity of 1585.5 mAh g-1 at 0.1 C and superior cycling stability with 0.012% capacity decay cycle-1 after 3000 cycles. More impressively, the assembled soft-packaged Li-S devices can exhibit the excellent stability under bending states. This binary active sites strategy provides a route to design the functional materials for modifying separators of Li-S batteries to improve the performance.

6.
Small ; : e2001100, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323466

RESUMO

Graphitic carbon nitride nanosheet (CNS) represents an attractive candidate for solar fuel production. However, the abundant defects in CNS lead to serious charge recombination and limit the photocatalytic performance. Herein, the synthesis of a CNS-covalent organic framework (CNS-COF) nanosheet composite is presented for the first time. CNS with significantly reduced defects is first obtained by rationally tuning the thermal exfoliation conditions of bulk carbon nitride. Subsequent modification of the CNS with trace COF nanosheet through chemical imine bonding can not only passivate the surface termination of carbon nitride in the boundary region, but also establish strong electronic coupling between these two components. As a consequence, enhanced charge separation and photocatalytic activity are realized on the resulting CNS-COF nanosheet composite. Under optimum conditions, hydrogen is evolved at a rate of 46.4 mmol g-1 h-1 . This corresponds to an apparent quantum efficiency of 31.8% at 425 nm, which is among the best values ever reported for carbon nitride-based materials.

7.
Metab Brain Dis ; 35(4): 627-635, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32140823

RESUMO

The study found that microRNAs play an important role in Parkinson's disease (PD). However, the function of MicroRNA-216a (miR-216a) in PD is unclear. Therefore, this experiment aimed to investigate the pathogenesis of miR-216a in PD. Using the toxicity of MPP+ to polyhexamine neurons, apoptosis of SH-SY5Y neuroblastoma cells was induced at different time by MPP+ to construct a stable acute PD cell model. The effects of DNA breakage, mitochondrial membrane potential (A ^ m), caspase-3 activity and nucleosome enrichment on cell apoptosis were detected by flow cytometry, TUNEL. MPP+ increased the toxic effects of dopaminergic neurons in a PD model. The introduction of miR-216a inhibited MPP + -induced neuronal apoptosis. The main manifestations were the decreased levels of positive rate of Tunel cells, caspase 3 activity and nucleosome enrichment factor. Bax was a direct target of miR-216a. In addition, Bax overexpression reversed the effects of miR-216a on neural cells. Bax downstream factors were also involved in miR-216a regulation of MPP + -triggered neuronal apoptosis. miR-216a regulated the progression of PD by regulating Bax, and miR-216a may be a potential target for PD.

8.
ACS Nano ; 14(4): 4014-4026, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32212674

RESUMO

Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) have exhibited regenerative capability in animal models of ischemia-reperfusion (I/R) acute kidney injury (AKI) and are considered as potential alternatives to direct MSC therapy. However, real-time in vivo imaging of MSC-EVs in renal I/R injury has yet to be established. Renal intracellular targets of MSC-EVs responsible for their regenerative effects also remain elusive. Here, we report that we real-time observed MSC-EVs specifically accumulated in the injured kidney and were taken up by renal proximal tubular epithelia cells (TECs) via DPA-SCP with aggregation-induced emission (AIE) characteristics. DPA-SCP precisely tracked the fate of MSC-EVs in a renal I/R injury mouse model for 72 h and exhibited superior spatiotemporal resolution and tracking ability to popular commercially available EV tracker PKH26. Further analysis revealed that the accumulated MSC-EVs stimulated mitochondrial antioxidant defense and ATP production via activating the Keap1-Nrf2 signaling pathway, which protected TECs against oxidative insult by reducing mitochondrial fragmentation, normalizing mitochondrial membrane potential, and increasing mitochondrial DNA copy number. Increased microRNA-200a-3p expression in renal TECs induced by MSC-EVs was identified as a regulatory mechanism contributing to the protective actions on mitochondria as well as stimulating the renal signal transduction pathways. In conclusion, MSC-EVs accumulated in the renal tubules during renal I/R injury and promoted the recovery of kidney function via activating the Keap1-Nrf2 signaling pathway and enhancing mitochondrial function of TECs. DPA-SCP with AIE characteristics allows noninvasive and precise in vivo visualization of MSC-EVs in kidney repair.

9.
Int J Biol Macromol ; 151: 312-321, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32084462

RESUMO

The characteristics of single domain and ease of gene manipulation of the single domain antibody (sdAb) make it suitable for affinity maturation in vitro. Since the affinity of antibodies can influence the immunoassays' sensitivity, a nanobody (Nb), the anti-ochratoxin A sdAb (AOA-sdAb), was herein selected as the model antibody to explore feasible approach for improving its affinity. Homology modeling and molecular docking were used to analyze the interaction between OTA and the AOA-sdAb. After alanine scanning verification, Gly53, Met79, Ser102, and Leu149 were determined as the key amino acids of the AOA-sdAb. Two site-directed saturated mutation libraries were constructed by two-site mutation against those four key amino acids. After biopanning and identification, a mutant Nb-G53Q&S102D was obtained with a half maximal inhibition concentration (IC50) of 0.29 ng/mL and a KD value of 52 nM, which is 1.4-fold and 1.36-fold lower than that of the original sdAb, respectively. The computer simulation analysis indicated that the hydrogen bond, hydrophobic interaction, and side chain steric hindrance of amino acid residues are critical for the binding affinity of the AOA-sdAb. Overall, the techniques shown in this study are effective ways at 'identifying residues involved in antigen binding' that can be altered by site-directed mutation.

10.
J Hazard Mater ; 387: 121678, 2020 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-31753666

RESUMO

Ochratoxin A (OTA) is a major concern for public health and the rapid detection of trace OTA in food is always a challenge. To minimize OTA exposure to consumers, a nanobody (Nb)-mediated förster resonance energy transfer (FRET)-based immunosensor using quantum dots (Nb-FRET immunosensor) was proposed for ultrasensitive, single-step and competitive detection of OTA in agro-products at present work. QDs of two sizes were covalently labeled with OTA and Nb, acting as the energy donor and acceptor, respectively. The free OTA competed with the donor to bind to acceptor, thus the FRET efficiency increased with the decrease of OTA concentration. The single-step assay could be finished in 5 min with a limit of detection of 5 pg/mL, which was attributed to the small size of Nb for shortening the effective FRET distance and improving the FRET efficiency. The Nb-FRET immunosensor exhibited high selectivity for OTA. Moreover, acceptable accuracy and precision were obtained in the analysis of cereals and confirmed by the liquid chromatography-tandem mass spectrometry. Thus the developed Nb-FRET immunosensor was demonstrated to be an efficient tool for ultrasensitive and rapid detection of OTA in cereals and provides a detection model for other toxic small molecules in food and environment.

11.
Polymers (Basel) ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527439

RESUMO

Inkjet printing on polyester fabric displays versatile environmental advantages. One of the significant benefits of inkjet printing is a dramatic enhancement of the printing quality. In this study, xanthan gum-a bio-based thickening agent accompanied by several salts-was adopted for the pretreatment of polyester fabric aiming at improving the sharpness and color depth of inkjet printed patterns. The influences of four metal salts (NaCl, KCl, CaCl2 and MgCl2) on inkjet printing performance were studied. More importantly, a quantitative method for evaluating the sharpness of an inkjet printed pattern was established according to the characteristics of anisotropy and isotropy of diffusion and adsorption of ink droplets on a fiber surface. Results showed that xanthan gum along with a low dosage of bivalent salts can significantly improve the color depth (K/S value) and sharpness of the printed polyester fabrics. It is feasible to evaluate the sharpness of inkjet printed polyester fabrics using a five-stage system, selecting the inkjet ellipse coefficient (T) and inkjet ellipse area (S), which can provide a quantitative and rapid evaluation method for defining inkjet printing.

12.
Materials (Basel) ; 12(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195599

RESUMO

This paper presents a simple and economical method for preparing durable anti-static functionalized inkjet prints by using P[St-BA-F6]-novel antistatic agents synthesized by an oxidative polymerization of styrene, butyl acrylate, and allyl alcohol polyether F6. The P[St-BA-F6] was characterized by gel permeation chromatography and Fourier transformation infrared spectroscopy. One bath pretreatment solution containing P[St-BA-F6] and pentaerythritol tetraacrylate (PETA) were applied to polyester fabrics before inkjet printing, in order to enhance the color yield and the anti-static properties. The pretreatment conditions, including the concentrations of P[St-BA-F6], curing temperature, and time, were optimized based on inkjet printed polyester fabrics. SEM (scanning electron microscope), XPS (X-ray photoelectron spectroscopy), XRD (X-ray diffractometer), TG (thermogravimetric), and DSC (differential scanning calorimetry) examined the fabrics. The results showed that the treated PET fabrics exhibited good applied performances, such as higher color yield, better dry rubbing fastness, lower electrostatic voltage, and durable anti-static properties, even after washing 10 times. These results can be attributed to alcohol polythene group (F6) and allyl group (PETA). PETA can be cross-linked with P[St-BA-F6] and PET fiber. The thermal stability of the treated fabric was lower than that of the untreated fabric, owing to the presence of resin film on the fiber surface.

13.
Chem Commun (Camb) ; 55(41): 5829-5832, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31041962

RESUMO

Modifying g-C3N4 with covalent organic frameworks (COFs) through imine linkage results in a dramatically enhanced visible-light-driven photocatalytic hydrogen evolution, which reached 10.1 mmol g-1 h-1 when 2 wt% Pt and triethanolamine were used as co-catalyst and sacrificial agent, respectively, corresponding to an apparent quantum efficiency (AQE) of 20.7% at 425 nm.

14.
Chem Commun (Camb) ; 55(40): 5728-5731, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31038493

RESUMO

A composite of single-crystalline Bi2WO6 and polycrystalline BiOCl with a high percentage of exposed (00l) facets was fabricated by the molten salt method (MSM) in the presence of polytetrafluoroethylene (PTFE). The photocatalytic activity of the composite was 17 and 70 times that of Bi2WO6 prepared by the MSM without PTFE and the traditional solid state reaction method, respectively.

15.
Huan Jing Ke Xue ; 40(3): 1101-1110, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087956

RESUMO

Atmospheric particle samples (PM1.0、PM2.5、PM10) were collected from three sampling sites (indoor and outdoor workplaces of a formal e-waste dismantling plant, and upwind area) in an arid area of Northwest China. The contents of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were analyzed using ICP-OES. Based on this data, the concentration levels, size distribution characteristics, and occupational exposure risks of heavy metals at the indoor and outdoor dismantling workplaces were studied. Particle analysis showed that Zn (4890 ng·m-3 indoors, 1245 ng·m-3 outdoors)、Pb (indoors 1201 ng·m-3, outdoors 240 ng·m-3), and Cu (indoors 1200 ng·m-3, outdoors 110 ng·m-3) showed higher pollution levels indoors and outdoors at the dismantling workplace. Moreover, the indoor concentration was much higher than that outdoors, indicating that the dismantling activity was the main cause of the high levels of heavy metal contamination. The indoor and outdoor air pollution characteristics were closely related to the types of electronic waste dismantled. Occupational exposure risk assessments showed that the total non-carcinogenic hazard quotient (HQ) of the indoor and outdoor dismantling workshops was 1.62×10-3, and 3.60×10-4, respectively, and the carcinogenic risk values were 2.69×10-7 and 2.59×10-9. Cd caused the greatest carcinogenic and non-carcinogenic risks at both indoor and outdoor dismantling workplaces, but it was still far below the limits (1.0) and acceptable ranges (1×10-6) stipulated by U.S. EPA, indicating that the health risks caused by heavy metals were minor or negligible. Heavy metals in the ambient particulate matter released from an adequately equipped and formally managed e-waste dismantling plant would not lead to any public health risk. The sedimentation characteristics of particulate heavy metals in different organs of the human respiratory system exhibited that the smaller the particle size was, the greater the proportion of deposition in the depths of the respiratory system was. Enterprises should make scientific and effective decisions on the respiratory health risks caused by such fine particles to the health of professional workers.

16.
Bioanalysis ; 11(5): 393-406, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30874444

RESUMO

AIM: Develop LC-MS/MS-based assays to measure total and free complement C5 in cynomolgus monkey serum as a target engagement biomarker for pharmacokinetic/pharmacodynamic correlation study. Materials & methods/results: The C5-specific signature peptide derived from pellet digestion of serum proteins with and without prior immunodepletion of the drug-bound C5 by protein A beads was quantified to assess free and total C5 levels, respectively. Conditions for immunodepletion by protein A were optimized to ensure complete depletion of IgGs (and drug-bound C5). The effect of sample dilution on drug-target dissociation and thus free C5 measurement was evaluated by applying a mathematical simulation. CONCLUSION: The procedure described here allows for the assessment of protein target engagement, aiding in pharmacokinetic/pharmacodynamic correlation analysis and human dose projection.


Assuntos
Proteínas Sanguíneas/metabolismo , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Macaca fascicularis
17.
ACS Nano ; 13(3): 3522-3533, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30844245

RESUMO

Extracellular vesicles (EVs) attract much attention in liver pathology because they regulate cell-cell communication and many pathophysiological events by transferring their cargos. Monitoring and understanding the in vivo fate and therapeutic capacity of these EVs is critical for the development and optimization of EV-based diagnosis and therapy. Herein, we demonstrate the use of an aggregation-induced emission luminogen, DPA-SCP, for the real-time tracking of EVs derived from human placenta-derived mesenchymal stem cells (MSCs) and their therapeutic effects in a mouse acute liver injury (ALI) model. In vitro, DPA-SCP does not alter the inherent characteristics of MSC-derived EVs and shows extremely low toxicity. Moreover, DPA-SCP exhibited superior labeling efficiency and tracking capability to the most popular commercial EV trackers, PKH26 and DiI. In vivo, DPA-SCP precisely and quantitatively tracked the behaviors of EVs for 7 days in the mouse ALI model without influencing their regenerative capacity and therapeutic efficacy. The therapeutic effects of EVs may attribute to their ability for reducing inflammatory cell infiltration, enhancing cell survival and antiapoptotic effects. In conclusion, DPA-SCP with an AIE signature serves as a favorable and safe tracker for in vivo real-time imaging of EVs in liver regeneration.

18.
Sens Actuators B Chem ; 279: 447-457, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30533973

RESUMO

There is an urgent need of sensitive bioanalytical platforms for sensitive and precise quantification of low-abundance microRNA targets in complex biological samples, including liquid biopsies of tumors. Many of current miRNA biosensing methods require laborious sample pretreatment procedures, including extraction of total RNA, which largely limits their biomedical and clinical applications. Herein we developed an integrated Microfluidic Exponential Rolling Circle Amplification (MERCA) platform for sensitive and specific detection of microRNAs directly in minimally processed samples. The MERCA system integrates and streamlines solid-phase miRNA isolation, miRNA-adapter ligation, and a dualphase exponential rolling circle amplification (eRCA) assay in one analytical workflow. By marrying the advantages of microfluidics in leveraging bioassay performance with the high sensitivity of eRCA, our method affords a remarkably low limit of detection at <10 zeptomole levels, with the ability to discriminate single-nucleotide difference. Using the MERCA chip, we demonstrated quantitative detection of miRNAs in total RNA, raw cell lysate, and cellderived exosomes. Comparing with the parallel TaqMan RT-qPCR measurements verified the adaptability of the MERCA system for detection of miRNA biomarkers in complex biological materials. In particular, high sensitivity of our method enables direct detection of low-level exosomal miRNAs in as few as 2 × 106 exosomes. Such analytical capability immediately addresses the unmet challenge in sample consumption, a key setback in clinical development of exosome-based liquid biopsies. Therefore, the MERCA would provide a useful platform to facilitate miRNA analysis in broad biological and clinical applications.

19.
Environ Sci Pollut Res Int ; 26(2): 1857-1870, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30460645

RESUMO

Polyurethane foam-based passive air sampler (PUF-PAS) and passive dry deposition sampler (PAS-DD) were adopted, for the first time ever in China, to investigate the atmospheric levels and spatial-temporal distributions of air burdens and dry deposition fluxes of 12 nitrated polycyclic aromatic hydrocarbons (NPAHs) during winter and summer seasons in a multiple site field campaign in a petrochemical industrialized capital city in Northwest China. The results showed that the highest air concentration and dry deposition fluxes of ∑12NPAHs occurred at a heavy traffic site among 18 sampling sites in both winter and summer season. The lowest air concentration and dry deposition fluxes were observed at the background site. The mean concentrations of ∑12NPAHs in the ambient air were 8.6 ± 8.1 ng m-3 in winter and 15 ± 11 ng m-3 in summer. The mean dry deposition fluxes of ∑12NPAHs were 1.8 × 103 ± 1.9 × 103 ng (m2 day)-1 in winter and 1.4 × 103 ± 1.3 × 103 ng (m2 day)-1 in summer, respectively. The total concentration of 12 NPAHs was mainly dominated by 1-nitro-naphthalene (1N-NAP) and 2-nitro-naphthalene(2N-NAP) in air, accounting for 32% in winter and 45% in summer of ∑12NPAHs. 7-Nitro-benzo [a] anthracene (7N-BaA) made the largest contribution to dry deposition fluxes of ∑12NPAHs, accounting for 28% in winter and 24% in summer. The ratios of ∑12NPAHs/∑15pPAHs (parent polycyclic aromatic hydrocarbons) were calculated to identify potential sources of NPAHs across the city. The results revealed that the main atmospheric air concentration and dry deposition fluxes of 12 NPAHs could be attributed to the primary emissions in winter and the secondary reaction formation in summer. The sources of primary emissions could be traced back to petrochemical, steel mills, as well as aluminum industries in winter and vehicle exhaust in summer. Higher ∑12NPAH/∑15pPAH concentration ratios in summer indicated that the oxidation of pPAHs contributed to the secondary formation of NPAHs via atmospheric chemical reactions in this petrochemical industrialized mountain-valley city.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , China , Desenvolvimento Industrial , Nitratos , Estações do Ano
20.
Acta Biomater ; 85: 94-105, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30550934

RESUMO

Mesenchymal stem cell (MSC) transplantation has emerged as a very promising strategy for the treatments of peripheral artery disease (PAD). However, MSC-based therapies are limited by low cell retention and survival rate in the ischemic zone. Small molecular (SM) hydrogels have shown attractive abilities to enhance the therapeutic effects of human MSCs via promoting their proliferation or maintaining their differentiation potential. Here, we designed and synthesized a new bioactive and biocompatible hydrogel, Nap-GFFYK-Thiol, using disulfide bonds as cleavable linkers to control the molecular self-assembly and we hypothesized this hydrogel could enhance the retention and engraftment of human placenta-derived MSCs (hP-MSCs) in a mouse ischemic hindlimb model. In vitro results demonstrated that the Nap-GFFYK-Thiol hydrogel increased cell viability through paracrine effects. Moreover, it enhanced the proangiogenic and anti-apoptotic effects of hP-MSCs. In vivo, Nap-GFFYK-Thiol hydrogel improved the hP-MSC retention in the murine ischemic hindlimb model as visualized by bioluminescence imaging. Furthermore, cotransplantation of hP-MSCs with hydrogel improved blood perfusion, leading to superior limb salvage. These therapeutic effects may attribute to reduced inflammatory cell infiltration, enhanced angiogenesis as well as suppressed collagen deposition. In conclusion, the Nap-GFFYK-Thiol hydrogel fabricated using disulfide bonds as cleavable linkers serves as an artificial niche for promoting hP-MSC survival and proangiogenic factor secretion in PAD therapy and thereby provide an alternative strategy for PAD therapy. STATEMENT OF SIGNIFICANCE: Although several phase I/II clinical trials of MSC-based treatments for critical limb ischemia (CLI) are ongoing, MSC-based therapies are still challenged by the low quality and quantity of cells in the ischemic zone, especially in cases of extensive or irreversible damage. Hydrogels have favorable biocompatibility and safety records in the medical field. In the current study, we engineered a new bioactive and biocompatible hydrogel, Nap-GFFYK-Thiol, using disulfide bonds as cleavable linkers to enhance the therapeutic efficacy of human placenta-derived MSCs (hP-MSCs) in mouse limb ischemia model. Notably, Nap-GFFYK-Thiol hydrogel acts as an artificial niche for promoting hP-MSC survival and proangiogenic factor secretion in PAD therapy, which further promoted the restoration of blood perfusion and regeneration of muscle cells. Considering the proangiogenic effect of Nap-GFFYK-Thiol on hP-MSCs, our results may provide a new strategy for the treatment of PAD.


Assuntos
Membro Posterior/irrigação sanguínea , Hidrogéis/farmacologia , Isquemia/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Peptídeos/farmacologia , Animais , Citoproteção/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Genes Reporter , Membro Posterior/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Inflamação/patologia , Isquemia/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacos , Comunicação Parácrina/efeitos dos fármacos , Peptídeos/síntese química , Peptídeos/química , Fenótipo , Placenta/citologia , Gravidez , Compostos de Sulfidrila/química , Resultado do Tratamento
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