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1.
Nat Biotechnol ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980910

RESUMO

RNA-binding proteins (RBPs) play an essential role in regulating the function of RNAs in a cellular context, but our ability to control RBP activity in time and space is limited. Here, we describe the engineering of LicV, a photoswitchable RBP that binds to a specific RNA sequence in response to blue light irradiation. When fused to various RNA effectors, LicV allows for optogenetic control of RNA localization, splicing, translation and stability in cell culture. Furthermore, LicV-assisted CRISPR-Cas systems allow for efficient and tunable photoswitchable regulation of transcription and genomic locus labeling. These data demonstrate that the photoswitchable RBP LicV can serve as a programmable scaffold for the spatiotemporal control of synthetic RNA effectors.

2.
J Rehabil Med ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037693

RESUMO

OBJECTIVE: To compare accelerated and delayed weight-bearing rehabilitation of anterior cruciate ligament reconstruction regarding clinical outcome measures of knee function (International Knee Documentation Committee Subjective Knee Form (IKDC), Lysholm Knee Scoring Scale, Tegner Activity Scale, and Knee Injury and Osteoarthritis Outcome Score (KOOS)), knee laxity, range of movement, quadriceps, and bone tunnel enlargement. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches of Embase, MEDLINE, CINAHL, and the Cochrane Library databases, from inception to February 2021, for studies comparing delayed or accelerated weight-bearing rehabilitation protocol after anterior cruciate ligament reconstruction in adult patients. RESULTS: Nine studies met the eligibility criteria. A meta-analysis revealed a higher risk of knee laxity in the accelerated weight-bearing group. Accelerated weight-bearing may be related to higher IKDC scores, while there was no statistical difference for Lysholm, Tegner, and KOOS scores at a follow-up within 2 years. Four of 5 studies reported no statistical difference for quadriceps strength and range of movement scores, while 2 studies reported bone tunnel enlargement in the accelerated weight-bearing group. CONCLUSION: This systematic review confirmed that accelerated weight-bearing caused more serious knee laxity and bone tunnel widening than delayed weight-bearing after anterior cruciate ligament reconstruction. We therefore recommend that clinicians should select postoperative rehabilitation programmes with caution.

3.
Langmuir ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995466

RESUMO

Understanding the interactions between the protein collagen and hydroxyapatite is of high importance for understanding biomineralization and bone formation. Here, we undertook a reductionist approach and studied the interactions between a short peptide and hydroxyapatite. The peptide was selected from a phage-display library for its high affinity to hydroxyapatite. To study its interactions with hydroxyapatite, we performed an alanine scan to determine the contribution of each residue. The interactions of the different peptide derivatives were studied using a quartz crystal microbalance with dissipation monitoring and with single-molecule force spectroscopy by atomic force microscopy. Our results suggest that the peptide binds via electrostatic interactions between cationic moieties of the peptide and the negatively charged groups on the crystal surface. Furthermore, our findings show that cationic residues have a crucial role in binding. Using molecular dynamics simulations, we show that the peptide structure is a contributing factor to the adhesion mechanism. These results suggest that even small conformational changes can have a significant effect on peptide adhesion. We suggest that a bent structure of the peptide allows it to strongly bind hydroxyapatite. The results presented in this study improve our understanding of peptide adhesion to hydroxyapatite. On top of physical interactions between the peptide and the surface, peptide structure contributes to adhesion. Unveiling these processes contributes to our understanding of more complex biological systems. Furthermore, it may help in the design of de novo peptides to be used as functional groups for modifying the surface of hydroxyapatite.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34997501

RESUMO

Photocatalysis with persulfate (PS) is an effective method for the degradation of degrading organic pollutants. In this study, Fe3O4/MIL-101(Fe), a magnetic heterojunction photocatalyst, was produced using a hydrothermal method. The material coupled with PS exhibited excellent removal efficiency for oxytetracycline (OTC) (87.1%, 1 h). And it has a wide range of applications, with good removal efficiency for OTC concentrations of 30 to 70 mg/L and pH values of 3 to 9. •SO4- and •OH played a major role in the OTC removal reaction and there was an Fe(III)/Fe(II) cycle during the reaction. With excellent stability and recoverability, the OTC removal efficiency decreased by only 4.29% after four cycles, and the Fe leaching did not exceed 0.035 mg/L per cycle. This study provides significant insights into the removal of organic pollutants from water bodies.

5.
Curr Microbiol ; 79(1): 1, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34878563

RESUMO

Despites Providencia heimbachae has been isolated from human, penguin, and bovine fetus, relatively little information is available regarding the pathogenicity and biologic characteristics of P. heimbachae. Here, we report that investigation of post-weaning diarrhea yielded bacterial isolates identified as P. heimbachae based on the biochemical tests and 16S ribosomal DNA sequence analysis. The two isolates were positive for utilization of Malonate, no gas production from glucose, and non-fermentation of D-mannitol, D-Galactose, and L-Rhamnose that were different from those of the type strain, and both of them have the ability of adhesion and invasion to IPEC-J2 cells, and were resistant to 21 out of the 41 antibiotics tested. In addition, the isolate 99101 was highly pathogenic to mice and piglets. Histopathology studies on nerve tissue of piglets that developed hindlimb paralysis showed microglia cell infiltration and neuron damage in the spinal cord. Notably, the strains could grow under low temperature (4 °C), which raise attention of a new risk factor for food safety. To the best of our knowledge, this is the first report of P. heimbachae strain caused post-weaning diarrhea in piglets in both natural and experimental conditions. These findings extended the knowledge of P. heimbachae as an important zoonotic agent, which should be given more attention during surveillance and diagnostics.

6.
Molecules ; 26(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885991

RESUMO

Inflammation caused by bacterial lipopolysaccharide (LPS) disrupts epithelial homeostasis and threatens both human and animal health. Therefore, the discovery and development of new anti-inflammatory drugs is urgently required. Plant-derived essential oils (EOs) have good antioxidant and anti-inflammatory activities. Thus, this study aims to screen and evaluate the effects of cinnamon oil and eucalyptus oil on anti-inflammatory activities. The associated evaluation indicators include body weight gain, visceral edema coefficient, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitrogen monoxide (NO), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), Urea, Crea, ALT, TLR4, MyD88, NF-κB, IκB-α, iNOS, and Mn-SOD. In addition, tissue injury was determined by H&E staining. The results revealed that cinnamon oil and eucalyptus oil suppressed inflammation by decreasing SOD, TNF-α, and NF-κB levels. We also found that cinnamon oil increased the level of GSH-Px, MDA, and Mn-SOD, as well as the visceral edema coefficient of the kidney and liver. Altogether, these findings illustrated that cinnamon oil and eucalyptus oil exhibited wide antioxidant and anti-inflammatory activities against LPS-induced inflammation.

7.
Neurologist ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34855663

RESUMO

BACKGROUND: As a common complication of cerebral infarction, hemorrhagic transformation (HT) often indicates a worse clinical outcome. The aim of this study was to explore the relationship between the platelet-to-neutrophil ratio (PNR) and HT in patients with acute cerebral infarction. METHODS: Patients with HT after acute cerebral infarction were enrolled in the HT group. Matched patients with acute cerebral infarction without HT were enrolled at the same time. All patients included in this study did not receive reperfusion therapy. The PNR was obtained on the second day of admission. Multivariate logistic analysis was used to evaluate the relationship between the PNR and HT. RESULTS: We collected data from a total of 137 patients: 61 patients with HT and 76 patients without HT. After adjusting for confounders, the PNR was independently associated with HT (odds ratio=0.922, 95% confidence interval: 0.891-0.955, P<0.05). The receiver operating characteristic curve demonstrated that the PNR could better predict HT (area under the curve=0.808, 95% confidence interval: 0.735-0.882, P<0.05). When the cut-off value of the PNR was 50.4765, the sensitivity was 70.5%, and the specificity was 82.9%. After stratifying the PNR to 50.4765, logistic analysis was performed again. The risk of HT in patients with a low PNR was 12.995 times that of patients with a high PNR. In patients without atrial fibrillation, the PNR was still independently related to HT. CONCLUSIONS: The PNR is a predictor of HT, and patients with a low PNR have a higher risk of HT.

8.
Soft Robot ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34890291

RESUMO

Soft adhesion is capable of attaching and bonding to rough surfaces and gripping nonplanar materials. It is preferable for material handling applications where safe interactions with external environments and enhanced adaptability to changing conditions are required. Soft electroadhesion (EA) is an emerging controllable adhesion technology that is especially suited to soft adhesion applications, but is prone to contact peeling that causes unwanted de-adhesion and cannot lift heavy objects unless the lifting force is applied parallel to the surface. Variable stiffness electroadhesion (VSEA) can be used to overcome these issues. Here a VSEA solution is developed by integrating electrostatic layer jamming and soft EA into a monolithic electrically controllable structure. The VSEA pad can achieve rapid response (within 1 s) and significant stiffness change (2200%), resist over four times the peeling force under a weight of 70 g, and generate 24.2%, 34.8%, and 49.3% greater adhesive forces on flat, convex, and concave surfaces, respectively. The promising gripping performance of the VSEA gripper was demonstrated by lifting and moving curved and flat objects. The VSEA concept and solution shown in this work may pave the way for the ready integration of EA into soft robotic systems and promote the broad application of EA technologies.

9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6183-6186, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892528

RESUMO

Affective Computing is a multidisciplinary area of research that allows computers to perform human emotion recognition, with potential applications in areas such as healthcare, gaming and intuitive human computer interface design. Hence, this paper proposes an affective interaction system using dry EEG-based Brain-Computer Interface and Virtual Reality (BCI-VR). The proposed BCI-VR system integrates existing low-cost consumer devices such as an EEG headband with frontal and temporal dry electrodes for brain signal acquisition, and a low-cost VR headset that houses an Android handphone. The handphone executes an in-house developed software that connects wirelessly to the headband, processes the acquired EEG signals, and displays VR content to elicit emotional responses. The proposed BCI-VR system was used to collect EEG data from 13 subjects while they watched VR content that elicits positive or negative emotional responses. EEG bandpower features were extracted to train Linear Discriminant and Support Vector Machine classifiers. The classification performances of these classifiers on this dataset and the results of a public dataset (SEED-IV) are then evaluated. The results in classifying positive vs negative emotions in both datasets (~66% for 2-class) show promise that positive and negative emotions can be detected by the proposed low cost BCIVR system, yielding nearly the same performance on the public dataset that used wet EEG electrodes. Hence the results show promise of the proposed BCI-VR system for real-time affective interaction applications in future.

10.
Front Psychol ; 12: 754168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899495

RESUMO

The purpose of this study was to explore theory of mind (ToM) differences in children with different birth orders (only-children, first-born children, and second-born children), and further explore the effect of cognitive verb training for only-children's ToM. Adopting the paradigm of false belief, Study 1 was conducted in which a sample of 120 children aged 3-6, including first-born children, second-born children (siblings aged 1-13 years), and only-children were tested. The results showed that (1) children aged 3-6 had significantly higher scores on first-order false-belief than second-order false-belief. (2) Controlling for age, the only-children scored significantly lower than the first-born children. In Study 2, 28 only-children aged 4-5 (13 in the experimental group and 15 in the control group) who initially failed in false-belief tasks were trained with the cognitive verb animations. Significant post-training improvements were observed for only-children who received training of animations embedded with cognitive verb. Those findings indicated that ToM of only-children was significantly worse than first-born children of two-child families, and linguistic training could facilitate ToM of only-children whose ToM were at a disadvantage.

11.
Water Sci Technol ; 84(12): 3891-3906, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34928850

RESUMO

A lanthanum modified sludge biochar chitosan (La-SBC-CS) microsphere was successfully synthesized by dropping sludge biochar (BC) and chitosan into a lanthanum chloride solution. Batch adsorption experiments were conducted to investigate the adsorption kinetics and isotherm. Application of continuous phosphate removal was achieved via lab-scale column reactors. The phosphate adsorption equilibrium data of the La-SBC-CS fitted well with the Freundlich isotherm, with a maximum adsorption amount of 81.54 mg p/g at 25 °C. Characterization of the adsorbent using scanning electron microscopy analysis (SEM), X-ray energy spectrum analysis (EDS), X-ray diffraction analysis (XRD) and Fourier infrared analysis (FTIR) techniques suggested that the possible adsorption mechanisms were electrostatic interaction, ligand exchange and complexation. The La-SBC-CS kept 76.37% phosphate removal efficiency after eight recycles. The results of continuous column reactor experiment demonstrated that the breakthrough time increased with an increase in adsorbent filling height, while it decreased with an increase in initial phosphate concentration or flow velocity. The Yoon model was applied to the continuous experimental data to predict breakthrough curves and determined the characteristic adsorption parameters for process design. This study indicated the potential for the practical application of La-SBC-CS in phosphate removal from wastewater.


Assuntos
Quitosana , Esgotos , Adsorção , Carvão Vegetal , Lantânio , Fosfatos
12.
Ann Transl Med ; 9(21): 1622, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34926666

RESUMO

Background: The aim of this study was to explore the value of using the YOLOv3 algorithm for detection and diagnosis of dental caries in oral photographs taken with mobile phones. Methods: Oral photographs taken with the mobile phones of 570 patients were used as 3 datasets: the augmented images (n=3,990), the enhanced images (n=3,990), and the combined augmented and enhanced images (n=7,980). Oral photographs taken by mobile phones from another 70 patients were used as an independent test set. We used the YOLOv3 network for migration learning for modelling. Diagnostic precision, recall, F1-score, and mean average precision (mAP) were calculated to obtain the detection and diagnostic performance of the YOLOv3 algorithm. Results: After 3 independent training, the mAP value of the original group YOLOv3 algorithm was 56.20%, in which the precision for primary caries recognition was 76.92%, recall was 49.59%, and F1-score was 0.60; the precision for secondary caries recognition was 91.67%, recall was 52.38%, and F1-score was 0.67. The mAP value of the enhance group algorithm was 66.69%, in which the precision for primary caries identification was 81.82%, recall was 52.07%, and F1-score was 0.64, and the precision for secondary caries identification was 100%, recall was 33.33%, and F1-score was 0.50. The mAP value of the comprehensive group algorithm was 85.48%, in which the precision for primary caries identification was 93.33%, recall was 69.42%, F1-score was 0.80, and the F1-score for secondary caries identification was 0.50; precision was 100%, recall was 52.38%, and F1-score was 0.69. Conclusions: The caries detection capability based on the YOLOv3 algorithm highlights the potential utility of deep learning in caries detection and diagnosis. Comparing the 3 experiments, the detection of the model trained after using image augmented and enhancement techniques was significantly improved.

13.
Micromachines (Basel) ; 12(12)2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34945362

RESUMO

This paper presents the theoretical thermal-mechanical modeling and parameter analyses of a novel three-dimensional (3D) electrothermal microgripper with three fingers. Each finger of the microgripper is composed of a bi-directional Z-shaped electrothermal actuator and a 3D U-shaped electrothermal actuator. The bi-directional Z-shaped electrothermal actuator provides the rectilinear motion in two directions. The novel 3D U-shaped electrothermal actuator offers motion with two degrees of freedom (DOFs) in the plane perpendicular to the movement of the Z-shaped actuator. As a result, each finger possesses 3D mobilities with three DOFs. Each beam of the actuators is heated externally with polyimide films. In this work, the static theoretical thermal-mechanical model of the 3D U-shaped electrothermal actuator is established. Finite-element analyses and experimental tests are conducted to verify and validate the model. With this model, parameter analyses are carried out to provide insight and guidance on further improving the 3D U-shaped actuator. Furthermore, a group of micro-manipulation experiments are conducted to demonstrate the flexibility and versality of the 3D microgripper on manipulate different types of small/micro-objects.

14.
Rice (N Y) ; 14(1): 98, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825994

RESUMO

Cold tolerance at the bud burst stage (CTB) is a key trait for direct-seeded rice. Although quantitative trait loci (QTL) affecting CTB in rice have been mapped using traditional linkage mapping and genome-wide association study (GWAS) methods, the underlying genes remain unknown. In this study, we evaluated the CTB phenotype of 339 cultivars in the Rice Diversity Panel II (RDP II) collection. GWAS identified four QTLs associated with CTB (qCTBs), distributed on chromosomes 1-3. Among them, qCTB-1-1 overlaps with Osa-miR319b, a known cold tolerance micro RNA gene. The other three qCTBs have not been reported. In addition, we characterised the candidate gene OsRab11C1 for qCTB-1-2 that encodes a Rab protein belonging to the small GTP-binding protein family. Overexpression of OsRab11C1 significantly reduced CTB, while gene knockout elevated CTB as well as cold tolerance at the seedling stage, suggesting that OsRab11C1 negatively regulates rice cold tolerance. Molecular analysis revealed that OsRab11C1 modulates cold tolerance by suppressing the abscisic acid signalling pathway and proline biosynthesis. Using RDP II and GWAS, we identified four qCTBs that are involved in CTB and determined the function of the candidate gene OsRab11C1 in cold tolerance. Our results demonstrate that OsRab11C1 is a negative regulator of cold tolerance and knocking out of the gene by genome-editing may provide enhanced cold tolerance in rice.

15.
Mol Ther Nucleic Acids ; 26: 1035-1050, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34786209

RESUMO

MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.

16.
Res Vet Sci ; 141: 180-189, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763254

RESUMO

Johne's disease, or paratuberculosis, is a chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This disease occurs worldwide and results in considerable economic losses in the livestock industry. There are no effective treatments for Johne's disease, so there is an urgent need to develop an efficient, economical, and stable vaccine for MAP control. Here, a live Escherichia coli (E. coli) surface display vaccine harboring the MAP3061c gene was developed through an ice nucleation protein (INP) surface display system. The experimental data demonstrated that MAP3061c has strong immunogenicity and that the surface displayed vaccine can stimulate mice to produce high levels of antibodies. Both CD4+ and CD8+ T cell counts as well as several cytokines - including IFN-γ, IL-4, IL-10, IL-17A and IL-23 - were significantly increased in the display vaccine group. Post-vaccination challenge with MAP in mice resulted in improved fitness of the mice as demonstrated by a lack of weight loss. Pathological results revealed that the surface display vaccine could reduce the degree of pathological damage and slowed the course of disease. Taken together, our data suggests that the E. coli carrier vaccine with surface-displayed MAP3061c elicits protective immunity against MAP, providing new insights into the development of a MAP vaccine.

17.
Comput Intell Neurosci ; 2021: 9210050, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721567

RESUMO

In this paper, a novel swarm-based metaheuristic algorithm is proposed, which is called tuna swarm optimization (TSO). The main inspiration for TSO is based on the cooperative foraging behavior of tuna swarm. The work mimics two foraging behaviors of tuna swarm, including spiral foraging and parabolic foraging, for developing an effective metaheuristic algorithm. The performance of TSO is evaluated by comparison with other metaheuristics on a set of benchmark functions and several real engineering problems. Sensitivity, scalability, robustness, and convergence analyses were used and combined with the Wilcoxon rank-sum test and Friedman test. The simulation results show that TSO performs better compared to other comparative algorithms.


Assuntos
Algoritmos , Simulação por Computador , Benchmarking , Engenharia
18.
J Am Chem Soc ; 143(45): 19112-19120, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34747617

RESUMO

Enantioselective hydroarylation of unactivated terminal akenes constitutes a prominent challenge in organic chemistry. Herein, we reported a Cp*Co(III)-catalyzed asymmetric hydroarylation of unactivated aliphatic terminal alkenes assisted by a new type of tailor-made amino acid ligands. Critical to the chiral induction was the engaging of a novel noncovalent interaction (NCI), which has seldomly been disclosed in the C-H activation area, arising from the molecular recognition among the organocobalt(III) intermediate, the coordinated alkene, and the well-designed chiral ligand. A broad range of C2-alkylated indoles were obtained in high yields and excellent enantioselectivities. DFT calculations revealed the reaction mechanism and elucidated the origins of chiral induction in the stereodetermining alkene insertion step.

19.
J Med Internet Res ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34806992

RESUMO

BACKGROUND: Given the permeation of social media through society, rumors spread faster than ever before, significantly complicating government response to public health emergencies like the COVID-19 pandemic. OBJECTIVE: We examined the characteristics and propagation of rumors during the early months of the COVID-19 pandemic in China and evaluated the effectiveness of health authorities' release of correction announcements. METHODS: We retrieved rumors widely circulating on social media in China during the early stages of the COVID-19 pandemic and assessed the effectiveness of official government clarifications and popular science articles refuting those rumors. RESULTS: We show that the number of rumors related to the domestic COVID-19 epidemic fluctuated widely in China between 12/1/2019 and 4/15/2020. Rumors mainly occurred in three provinces: Hubei, Zhejiang, and Guangxi. Personal social media accounts constituted the major source of media reports of the four most widely distributed rumors (71.7%, 92.4%, 99.2% and 99.7%). The number of rumors circulating was positively associated with the severity of the COVID-19 epidemic (rs=0.88, 95% CI: 0.81-0.93). Release of correction articles was associated with a substantial decrease in the proportion of rumor reports compared to accurate reports. The proportion of negative sentiments appearing among comments by citizens in response to media articles disseminating rumors and disseminating correct information did not differ significantly. CONCLUSIONS: Our results highlight the importance and urgency to monitor and correct false or misleading reports on websites and personal social media accounts. Circulation of rumors can influence public health, and governmental bodies should establish guidelines to monitor and mitigate the negative impact of such rumors.

20.
J Control Release ; 341: 16-30, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34793917

RESUMO

Imbalance between the activities of pro-inflammatory M1 and anti-inflammatory M2 macrophages in rheumatoid arthritis (RA) induces synovial inflammation and autoimmunity, leading to joint damage. Here we encapsulated a plasmid DNA encoding the anti-inflammatory cytokine interleukin-10 (IL-10 pDNA) and the chemotherapeutic drug betamethasone sodium phosphate (BSP) into biomimetic vector M2 exosomes (M2 Exo) derived from M2-type macrophages. We demonstrate that the loaded exosomes target and reduce inflammation for combined therapy against RA. The in vitro efficiency of the M2 Exo/pDNA/BSP co-delivery system was attributed to the synergistic effect of IL-10 pDNA and BSP, which also promoted M1-to-M2 macrophage polarization by reducing the secretion of pro-inflammatory cytokines (IL-1ß, TNF-α) and increasing the expression of IL-10 cytokine. In a mouse model of RA, M2 Exo/pDNA/BSP showed good accumulation at inflamed joint sites, high anti-inflammatory activity, and potent therapeutic effect. The delivery system was non-toxic both in vitro and in vivo. Thus, this system may serve as a promising biocompatible drug carrier and anti-inflammatory agent for RA treatment based on M1-to-M2 macrophage re-polarization.

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