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1.
Food Chem ; 356: 129678, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33812185

RESUMO

This study investigated the effect of frozen storage periods (0, 2, 4, 6, or 8 weeks) of raw meat and stewing on the flavor of chicken broth. With the increased storage duration of frozen raw material, the contents of the free amino acids, nucleotides and mineral elements in the broth decreased significantly, especially within the first 4 weeks, and then increased significantly. Meanwhile, the volatile compounds showed the reverse trend. The results from the E-nose, E-tongue and sensory evaluation indicated a progressive difference in overall flavor profiles between the samples. The sensory scores of the meaty and fatty traits reached a maximum as raw chicken meat was stored for 4 weeks at -18 °C, which should be related to the increased contents of aldehydes and 2-pentyl furan. Overall, the limited storage duration of frozen raw meat can enhance the flavor of chicken broth.

2.
Acta Pharmacol Sin ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833406

RESUMO

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

3.
Front Immunol ; 12: 609421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767695

RESUMO

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.

4.
Chem Rev ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33667075

RESUMO

The past decade has witnessed ongoing progress in precision medicine to improve human health. As an emerging diagnostic technique, liquid biopsy can provide real-time, comprehensive, dynamic physiological and pathological information in a noninvasive manner, opening a new window for precision medicine. Liquid biopsy depends on the sensitive and reliable detection of circulating targets (e.g., cells, extracellular vesicles, proteins, microRNAs) from body fluids, the performance of which is largely governed by recognition ligands. Aptamers are single-stranded functional oligonucleotides, capable of folding into unique tertiary structures to bind to their targets with superior specificity and affinity. Their mature evolution procedure, facile modification, and affinity regulation, as well as versatile structural design and engineering, make aptamers ideal recognition ligands for liquid biopsy. In this review, we present a broad overview of aptamer-based liquid biopsy techniques for precision medicine. We begin with recent advances in aptamer selection, followed by a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification. We will further describe aptamer-based micro-/nanoisolation platforms, aptamer-enabled release methods, and aptamer-assisted signal amplification and detection strategies. Finally, we present our perspectives regarding the opportunities and challenges of aptamer-based liquid biopsy for precision medicine.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33651293

RESUMO

Preferential removal of phosphate from aqueous was conducted by a novel biomass-based nanocomposite (EP-N+-Zr) with encapsulated hydrous zirconium oxide, and the biopolymer EP-N+-Zr features were described. EP-N+-Zr exhibited high selective sequestration toward phosphate when humic acid or other competing anions (Cl-, SO42-, NO3-, ClO4-) coexisted at relatively high levels. Such excellent performance of EP-N+-Zr was attributed to its specific two site structures; the embedded HZO nanoparticles and quaternary ammonia groups [N+(CH2CH3)3Cl-] bonded inside the biomass-Enteromorpha prolifera, which facilitated preferable capture towards phosphate through specific affinity and nonspecific preconcentration of phosphate ions on the basis of the ion exchange, respectively. The maximum adsorption capacity of phosphate (20 °C) as calculated by Langmuir model was 88.5 mg(P)/g. Regeneration tests showed that EP-N+-Zr could be recycled at least five times without noticeable capacity losses using binary NaOH-NaCl as eluent.

6.
Environ Pollut ; 276: 116716, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592440

RESUMO

Production of minor crop varieties often requires intensive pesticide use, which raises serious concerns over food safety and human health. Chaenomeles speciosa (Sweet) Nakai as one of the representative of this kind of crops is therefore used for investigating the residue behavior of fenpropathrin and emamectin benzoate, a synthetic pyrethroid and macrocyclic lactone widely used as an insecticide, respectively, from cultivation to C. speciosa postharvest processing. Results showed that the degradation trends of those selected insecticides in C. speciosa followed first-order kinetics with an average half-life (t1/2) of 3.7-4.1 days and a dissipation rate of 97% over 14 days. The terminal residues of fenpropathrin and emamectin benzoate at 120 and 3 g a.i./ha were below the U.S Environmental Protection Agency (FAD, 1.00 mg/kg) and European Union (EU, 0.01 mg/kg) maximum residue limits (MRLs) in papaya species, respectively, when measured 14 days after the final application, which suggested that the use of these insecticides was safe for humans. Postharvest processing procedure resulted in a |90% reduction of the insecticides. Moreover, the hazard quotient (HQ) for C. speciosa decoction (with processing factors) indicated an acceptable risk for human consumption. These findings provide the scientific evidence of reasonable application and risk assessment of the selected pesticide residues in C. speciosa.


Assuntos
Inseticidas , Resíduos de Praguicidas , Piretrinas , Rosaceae , Humanos , Inseticidas/análise , Ivermectina/análogos & derivados , Ivermectina/análise , Resíduos de Praguicidas/análise , Piretrinas/análise
7.
Proc Natl Acad Sci U S A ; 118(8)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33558418

RESUMO

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

8.
Nanoscale ; 13(9): 4774-4784, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33576757

RESUMO

GNA002, a novel EZH2 inhibitor, exhibits significant anticancer efficiency in solid malignant tumor therapy; however, its poor water solubility and low enrichment at tumor sites limit its clinical application and translation. In this study, an original pH-sensitive nanocarrier (cyclo (RGDyCSH) (cRGD)-poly (ethylene glycol) (PEG)-hydrazine (Hyd)-hexa-arginine (R6)-stearic acid (SA)) was designed to precisely deliver GNA002 into the nuclei of cancer cells. The PEG-modified hydrophilic shell of the spherical GNA002-loaded nanoparticles with a mean size of 143.13 ± 0.20 nm effectively facilitated the passive target of tumor tissues and prolonged the blood circulation time. Meanwhile, cRGD was used as the active targeting ligand, which promoted the accumulation of the nanoparticles in cancer cells via ανß3-receptor-mediated endocytosis. Furthermore, the acidic environment of lysosomes triggered the rupture of the pH-sensitive hydrazine bond and the rapid formation of penetrating peptide R6-shelled secondary nanoparticles, thus enabling the lysosomal escape of the nanoparticles and the ultimate R6-mediated nuclear-targeted delivery of GNA002. Consequently, the nuclear-enriched GNA002 effectively enhanced the cytotoxicity against cancer cells both in vitro and in vivo, thus providing an original and promising drug delivery system for the targeted delivery of GNA002.

9.
J Hazard Mater ; 413: 125413, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33611033

RESUMO

Herein, we attempted to apply an exhausted magnetic biochar with adsorbed Cu2+ (Cu-Fe@BRC) directly as a PMS activator and explored the feasibility of this attempt. Density functional theory (DFT) and electrochemical analysis illuminated the adsorbed Cu2+ in Cu-Fe@BRC improved PMS activation and NOR degradation efficiency by elevating the adsorption capacity of PMS and performance of electron transfer. About 91.47% of norfloxacin (NOR) was rapidly degraded in Cu-Fe@BRC/PMS system with low Fe and Cu leaching. An in-depth mechanistic study was conducted with radical scavenging, radical capturing and solvent exchange, which demonstrated that the adsorbed Cu2+ could facilitate the formation of both different radicals and non-radical. Importantly, Cu-Fe@BRC can maintain a long-term stable operation and excellent catalytic performance in surface water treatment. The potential toxicity of by-product generated in the NOR degradation process was also predicated, and results suggested that most identified by-products were less toxic than NOR itself. Notably, the preparation cost of exhausted adsorbent-based catalysts could be negligible, so the expenditure of the corresponding oxidation process is reduced accordingly. Based on above, this work provides not only a low-cost exhausted biochar-based catalyst for water purification but also the insight into the PMS activation by adsorbed transition metal ions.

10.
Chemosphere ; 274: 129783, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33545591

RESUMO

In this study, nano-sized CoFe2O4 composites were prepared through co-precipitation process. Then the phosphorus-doped strong magnetic graphitic carbon nitride hybrids composites (P-CoFe2O4@GCN) was stemmed from the CoFe2O4 composites via the thermal polymerization method. The TEM results show that the CoFe2O4 nanoparticles have been successfully embedded into the graphitic carbon nitride (GCN). The BET specific surface area of P-CoFe2O4@GCN-1 could reach 36.91 m2/g, which was 5.38 times higher than that of GCN. Thus, it provided sufficient reaction active sites to enhance the photocatalytic activity for tetracycline (TC) decomposition. The results from the photocatalytic experiments showed that the degradation efficiency of TC by P-CoFe2O4@GCN-1 could reach 96.2% within 60 min, which is 3.19 times higher than that of GCN. The h+, O2•- and •OH radicals detected by the electron spin resonance (ESR) were responsible for the TC decomposition in the photocatalytic reaction system. Persulfate (PS) can further activate the hybrid mixture system, and the fitting model predicted by the response surface methodology (RSM) indicated that the maximum tetracycline removal could reach 99.6% within 30 min. In addition, the degradation intermediates of TC were detected by HPLC-MS and the photodegradation mechanism was discussed.

11.
Sci Total Environ ; 774: 145751, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33611005

RESUMO

As the dominant hazardous waste discharged from petroleum industry, the pyrolysis features of the upstream oily sludge (UOS) were scrutinized by way of TGA/DSC. The pyrolysis kinetics model of UOS was systematically constructed by sectionalized single-step reaction approach (SSRA) and distributed activation energy model (DAEM), and the data reproducibility was further evaluated. The results showed that when the pyrolysis operation temperature interval was set from 380 K to 1170 K, two weigh loss step, two endo/exothermic regions and three significant mass-loss peak were respectively emerged in TG, DSC and DTG curves, based on which the TG curves could be sectionalized into three stages. Attributing to the ∆E/Eα¯ value of each stage was higher than 10% but lower than 20% derived from the activation energy assessment, it is not only revealed three multi-step reactions were carried out in sequence with an individual dominant single-step reaction which was sufficient for the SSRA utilization, but also displayed a well fitted by the Gaussian distribution which satisfied the requirement of DAEM implementation. Based on the five-step construction procedure introduced in this paper, pyrolysis kinetics model of UOS could be successful established and interpret as SSRA-based and DAEM-based piecewise function. The latter exhibited a better performance on the data reproduction than the former because the nRSS value of the reproduced data derived from DAEM-based model was lower than 1.86%. The higher mathematical flexibility of DAEM-based model function was the major attribution to a better data reproducibility, also, it possessed a potential ability in predicting the reaction rate at an arbitrary reaction temperature once the heating ratio was preset.

12.
ACS Appl Mater Interfaces ; 13(7): 8042-8048, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33576594

RESUMO

Biomarkers based on DNA methylation have attracted wide attention in biomedical research due to their potential clinical value. Therefore, a sensitive and accurate method for DNA methylation detection is highly desirable for the discovery and diagnostics of human diseases, especially cancers. Here, an integrated, low-cost, and portable point-of-care (POC) device is presented to analyze DNA methylation, which integrates the process of pyrosequencing in a digital microfluidic chip. Without additional equipment and complicated operation, droplets are manipulated by patterned electrodes with individually programmed control. The system exhibited an excellent sensitivity with a limit of detection (LOD) of 10 pg and a comparable checkout down to 5% methylation level within 30 min, which offered a potential substitute for the detection of DNA methylation. With the advantages of portability, ease of use, high accuracy, and low cost, the POC platform shows great potential for the analysis of tumor-specific circulating DNA.


Assuntos
Automação , DNA/análise , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Sistemas Automatizados de Assistência Junto ao Leito , Biomarcadores/análise , DNA/genética , Metilação de DNA , Humanos , Técnicas Analíticas Microfluídicas/instrumentação
13.
Proc Natl Acad Sci U S A ; 118(10)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33619176

RESUMO

Reconstructing the history of biodiversity has been hindered by often-separate analyses of stem and crown groups of the clades in question that are not easily understood within the same unified evolutionary framework. Here, we investigate the evolutionary history of birds by analyzing three supertrees that combine published phylogenies of both stem and crown birds. Our analyses reveal three distinct large-scale increases in the diversification rate across bird evolutionary history. The first increase, which began between 160 and 170 Ma and reached its peak between 130 and 135 Ma, corresponds to an accelerated morphological evolutionary rate associated with the locomotory systems among early stem birds. This radiation resulted in morphospace occupation that is larger and different from their close dinosaurian relatives, demonstrating the occurrence of a radiation among early stem birds. The second increase, which started ∼90 Ma and reached its peak between 65 and 55 Ma, is associated with rapid evolution of the cranial skeleton among early crown birds, driven differently from the first radiation. The third increase, which occurred after ∼40 to 45 Ma, has yet to be supported by quantitative morphological data but gains some support from the fossil record. Our analyses indicate that the bird biodiversity evolution was influenced mainly by long-term climatic changes and also by major paleobiological events such as the Cretaceous-Paleogene (K-Pg) extinction.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33587718

RESUMO

With the rapid evolution of wireless mobile devices, there emerges an increased need to design effective collaboration mechanisms between intelligent agents to gradually approach the final collective objective by continuously learning from the environment based on their individual observations. In this regard, independent reinforcement learning (IRL) is often deployed in multiagent collaboration to alleviate the problem of a nonstationary learning environment. However, behavioral strategies of intelligent agents in IRL can be formulated only upon their local individual observations of the global environment, and appropriate communication mechanisms must be introduced to reduce their behavioral localities. In this article, we address the problem of communication between intelligent agents in IRL by jointly adopting mechanisms with two different scales. For the large scale, we introduce the stigmergy mechanism as an indirect communication bridge between independent learning agents, and carefully design a mathematical method to indicate the impact of digital pheromone. For the small scale, we propose a conflict-avoidance mechanism between adjacent agents by implementing an additionally embedded neural network to provide more opportunities for participants with higher action priorities. In addition, we present a federal training method to effectively optimize the neural network of each agent in a decentralized manner. Finally, we establish a simulation scenario in which a number of mobile agents in a certain area move automatically to form a specified target shape. Extensive simulations demonstrate the effectiveness of our proposed method.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33444144

RESUMO

Recurrent neural networks (RNNs) have gained tremendous popularity in almost every sequence modeling task. Despite the effort, these kinds of discrete unstructured data, such as texts, audio, and videos, are still difficult to be embedded in the feature space. Studies in improving the neural networks have accelerated since the introduction of more complex or deeper architectures. The improvements of previous methods are highly dependent on the model at the expense of huge computational sources. However, few of them pay attention to the algorithm. In this article, we bridge the Taylor series with the construction of RNN. Training RNN can be considered as a parameter estimate for the Taylor series. However, we found that there is a discrete term called the remainder in the finite Taylor series that cannot be optimized using gradient descent, which is part of the reason for the truncation error and the model falling into the local optimal solution. To address this, we propose a training algorithm that estimates the range of remainder and introduces the remainder obtained by sampling in this continuous space into the RNN to assist in optimizing the parameters. Notably, the performance of RNN can be improved without changing the RNN architecture in the testing phase. We demonstrate that our approach is able to achieve state-of-the-art performance in action recognition and cross-modal retrieval tasks.

16.
Sci Total Environ ; 763: 142958, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33498113

RESUMO

Three-dimensional graphene aerogel materials used for treatment of oily wastewater with sophisticated composition remains a challenge due to volume shrinkage, resulting in single-function and low adsorption capacity. In this work, renewable Enteromorpha was introduced into the graphene aerogel via facile hydrothermal-freeze casting treatment, forming the compression, ultralight and amphiphilic adsorbent for oil spill cleanup and water pollution remediation. Meanwhile, further freeze casting avoids aerogel collapse for capillary tension during drying and produce more hierarchical pores. As for oil spill clean up, the Enteromorpha modified graphene aerogel (EGA) exhibits excellent adsorption capacity towards oil and organic solvents than pristine graphene aerogel (GA). Even after several cycles by compression and heat treatment, it still has a stable adsorption capacity for oil and organic solvents. The EGA also showed high ability to absorb water-soluble pollutants, such as dyes through hydrogen bonding and electrostatic reactions between dye molecules and aerogel. The facile strategy to fabricate the Enteromorpha-based amphiphilic EGA broadens the applications in water treatment through the high-value utilization of Enteromorpha.


Assuntos
Grafite , Poluição por Petróleo , Poluentes Químicos da Água , Purificação da Água , Poluição por Petróleo/análise , Água , Poluentes Químicos da Água/análise
17.
Food Res Int ; 139: 109834, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33509459

RESUMO

High-pressure processing (HPP) can modify the construction of interfacial proteins (IPs) to improve the properties of reduced-fat and reduced-salt (RFRS) meat batters. In this study, the relationship between the construction of IPs and their solubility at fat droplet/water interface in RFRS meat batters with HPP treatments was investigated. When 200 MPa for 2 min was applied, the IPs exhibited the highest solubility due to a high concentration of absorbed myosin with the content of random coil 65.62%, but the particle diameter was in reverse. The microscopy revealed the depolymerization of IPs occurred at low pressure, while macromolecular aggregates were produced as the cross-linking of IPs to some degree at pressure ≥ 200 MPa. This phenomenon was supported by the result of SDS-PAGE and the sulfhydryl of IPs. In conclusion, the HPP induced solubility alteration of IPs was achieved by modifying their construction through adjusting the secondary structures and regulating bond interactions.

18.
Food Chem Toxicol ; 149: 111970, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33421459

RESUMO

Studies have shown that the central renin-angiotensin system is involved in neurological disorders. Our previous studies have demonstrated that angiotensin II receptor type 1 (AT1R) in the brain could be a potential target against methamphetamine (METH) use disorder. The present study was designed to investigate the underlying mechanisms of the inhibitory effect of AT1R on various behavioural effects of METH. We first examined the effect of AT1R antagonist, candesartan cilexetil (CAN), on behavioural and neurotoxic effects of METH. Furthermore, we studied the role of phospholipase C beta 1 (PLCß1) blockade behavioural and neurotoxic effects of METH. The results showed that CAN significantly attenuated METH-induced behavioral disorders and neurotoxicity associated with increased oxidative stress. AT1R and PLCß1 were significantly upregulated in vivo and in vitro. Inhibition of PLCß1 effectively alleviated METH-induced neurotoxicity and METH self-administration (SA) by central blockade of the PLCß1 involved signalling pathway. PLCß1 blockade significantly decreased the reinforcing and motivation effects of METH. PLCß1 involved signalling pathway, as well as a more specific role of PLCß1, involved the inhibitory effects of CAN on METH-induced behavioural dysfunction and neurotoxicity. Collectively, our findings reveal a novel role of PLCß1 in METH-induced neurotoxicity and METH use disorder.

19.
Environ Sci Pollut Res Int ; 28(13): 16655-16662, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33389468

RESUMO

Numerous natural preparations in traditional Chinese medicine are prepared as decoctions. Processing factors (PFs) comparing the levels of pesticide residues in decoctions to those in the corresponding unprocessed products should be considered in exposure assessments. Thus, this study determined the residue levels of six pesticides (chlorpyrifos, phoxim, imidacloprid, thiamethoxam, fenpropathrin, and emamectin benzoate), as well as 3,5,6-trichloropyridinol, the primary metabolite of chlorpyrifos, and clothianidin, the main metabolite of thiamethoxam in Baishao, Paeoniae radix lactiflora (Fam. Ranunculaceae). The results showed that significant time-response effects were present for the release of pesticides from P. radix. The PFs calculated were < 1, indicating a significant reduction in pesticide residues after TCM processing. The water solubility and partition coefficient values of the pesticides may have played a basic role in the dissipation of the residues during the TCM decocting process. A risk assessment based on the hazard quotient with PFs revealed that exposure to pesticide residues in P. radix was far below the levels that might pose a health risk. In conclusion, the results presented here are of theoretical and practical value for the safety evaluation of TCMs.


Assuntos
Paeonia , Resíduos de Praguicidas , Praguicidas , Medicina Tradicional Chinesa , Resíduos de Praguicidas/análise , Medição de Risco
20.
Exp Cell Res ; 399(1): 112451, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33352191

RESUMO

The use of chimeric antigen receptor-modified T cells (CAR T cells) is an effective therapy for advanced cancer, especially hematological malignancies, and this method has attracted widespread attention in the last several years. The type, number and vitality of the effector cells clearly play important roles in this approach. In this study, to expand the possibility of curing cancer through adoptive cell therapy (ACT), we developed a novel method for effectively obtaining abundant T cells in vitro. The fusion proteins of three cytokines, SA-hIL-2, SA-hIL-7 and SA-hIL-21, were anchored onto biotin magnetic beads to increase the number of cytokines on the surface of the magnetic beads, which increased the local concentration of cytokines and thus promoted the binding of cytokines to T cells. Next, we examined the effects of these modified magnetic beads on the proliferation rate of T cells and CD19 CAR T cells. In this study, we report the expression and purification of the active bifunctional fusion proteins SA-hIL-2, SA-hIL-7 and SA-hIL-21, which were bound to biotin magnetic beads to develop a platform that was employed to increase the local concentration of cytokines. When the cells had been cultured for 14 days, the proliferation rate of the CD3+ T cells in the group that received cytokine-coupled biotin magnetic beads (Beads-SA-CK) was higher than that of the cells in the groups that received soluble cytokines (Soluble-SA-CK) and that of the cells in the standard group (Standard-CK). We speculate that this difference may be the result of the increased expression of Bcl-2 and the increased phosphorylation of Stat5. Moreover, our results preliminarily indicate that compared with the other two treatments, Soluble-SA-CK and Standard-CK, adding cytokine-coupled biotin magnetic beads more effectively increases the proliferation rate of CD19 CAR-T cells. As expected, the CD19 CAR-T cells stimulated by Beads-SA-CK had a stronger anticancer effect than the cells stimulated by the other two treatments. An effective method of preparing abundant T cells in vitro was developed, and it may provide a novel strategy for ACT.

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