We previously identified an immunomodulatory role of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) in asthmatic inflammation. Mitochondrial transfer from bone ...marrow MSCs to epithelial cells can result in the attenuation of acute lung injury in mice. However, the effects of mitochondrial transfer from iPSC-MSCs to epithelial cells in asthma and the mechanisms underlying these effects are unclear. We found that iPSC-MSC transplantation significantly reduced T helper 2 cytokines, attenuated the mitochondrial dysfunction of epithelial cells, and alleviated asthma inflammation in mice. Tunneling nanotubes (TNTs) were formed between iPSC-MSCs and epithelial cells, and mitochondrial transfer from iPSC-MSCs to epithelial cells via TNTs was observed both in vitro and in mice. Overexpression or silencing of connexin 43 (CX43) in iPSC-MSCs demonstrated that CX43 plays a critical role in the regulation of TNT formation by mediating mitochondrial transfer between iPSC-MSCs and epithelial cells. This study provides a therapeutic strategy for targeting asthma inflammation.
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•iPSC-MSCs attenuate asthma inflammation and protect epithelial cells•The protection of iPSC-MSCs is attributable to mitochondrial transfer via TNTs•CX43-mediated TNT formation regulates the mitochondrial donation of iPSC-MSCs
In this article, Fu, Lian, and colleagues show that mesenchymal stem cells derived from human induced pluripotent stem cells can transfer their mitochondria to rescue the injured bronchial epithelial cells, which attenuates asthma inflammation. Connexin 43, a component of gap junctions, plays a critical role during the process of mitochondrial transfer by regulating intercellular tunneling nanotube formation.
In this paper, a novel topology preserving non-negative matrix factorization (TPNMF) method is proposed for face recognition. We derive the TPNMF model from original NMF algorithm by preserving local ...topology structure. The TPNMF is based on minimizing the constraint gradient distance in the high-dimensional space. Compared with L 2 distance, the gradient distance is able to reveal latent manifold structure of face patterns. By using TPNMF decomposition, the high-dimensional face space is transformed into a local topology preserving subspace for face recognition. In comparison with PCA, LDA, and original NMF, which search only the Euclidean structure of face space, the proposed TPNMF finds an embedding that preserves local topology information, such as edges and texture. Theoretical analysis and derivation given also validate the property of TPNMF. Experimental results on three different databases, containing more than 12 000 face images under varying in lighting, facial expression, and pose, show that the proposed TPNMF approach provides a better representation of face patterns and achieves higher recognition rates than NMF.
Energy is essential to human daily functioning and performance. However, the association of mental energy with athletes' performance has rarely been examined. We attempted to examine the ...pre-competition mental energy-performance relationships by two studies. Study 1 administered Athletic Mental Energy Scale (AMES, Lu et al., 2018) to nine elite physically-disabled table tennis players one day before competition in 5 international tournaments. Then, we collected their subjective performance after each competition. In Study 2, we sampled 77 National-level physically-disabled table tennis players and examined the pre-competition mental energy-performance relationship as the procedure in Study 1. Results from Study 1 provided initial findings of how pre-competition mental energy is associated with performance and portrayed in elite physically-disabled table tennis players. Results from Study 2 further confirmed the pre-competition mental energy- performance relationships. We suggested future studies to examine the mental energy-performance relationships in physically-disabled and abled athletes and different sports.
Defects play significant roles in spin-current-related physical processes in intrinsic ferromagnetic semiconductors (FMSs), which are great promise for spintronics applications. However, current ...defect calculation methods cannot be used to investigate charged defects in FMSs due to the spin polarization of both the charged defect states and ionized carriers, which is not well treated in current defect calculation methods. In order to solve this problem, we propose a spin-distinguishable charge correction (SDCC) method that uses spin-polarized band edge charge density instead of spin-unpolarized uniform background charge density as the compensating charge for charged defects. We apply our method to study the defect properties of CrI3 monolayer and find it can be doped n-type under the Cr-rich growth condition but difficult to be doped p-type. The SDCC method proposed here is generally suitable for all FMSs, which will be useful for the studies of defect properties of magnetic semiconductors.
larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including ...macrophages, around the lesion that produces an "immunosuppressive" microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against
infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of
, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68
macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9
proinflammatory (M1 phenotype) and CD163
anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore,
-infected mice exhibited a massive increase in macrophage (F4/80
) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11b
F4/80
MoMFs) that preferentially differentiated into the M1 phenotype (iNOS
) at the early stage of
infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206
) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before
infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of
metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.
In the current study, the effects of extrusion temperatures on the extrudability, microstructure, recrystallization behavior and mechanical properties of the Mg–3.0Zn–0.2Ca–0.5Y alloy have been ...systematically investigated. The results show that the magnesium alloy bars with excellent mechanical properties are obtained at the extrusion temperature above 523K. Both the dynamic recrystallized grain size and fraction increase with an increase in the deformation temperature. The MgY phase particles (>1μm) contribute to increasing DRX fraction, while the finer I-phase precipitates exert a pinning effect on the movement of grain boundaries and thus suppress the grain growth. The competitive mechanism between the particle-stimulated nucleation and grain boundary pinning determines the final microstructure that strongly affects the mechanical properties of the extruded alloys. The yield strength is improved with the decrease of the DRX grain size by grain boundary strengthening, and the ductility is increased by the enhanced work hardening ability with the increase of the DRX fraction.
A facile method, post-synthetic exchange of modulators (PSEm), has been demonstrated here to prepare chiral metal-organic frameworks for enantioseparation. Based on this method, three chiral porous ...Zr-based metal-organic frameworks have been prepared through exchanging the coordinated modulators on metal clusters of MOFs with commercially available chiral carboxylic acid molecules. In addition, the obtained materials show enantioselectivity toward three different enantiomers, which presents a proof of concept for the design of MOF materials for enantioseparation by an easy and low-cost method.
A facile post-synthetic modification method has been demonstrated here to prepare chiral metal-organic frameworks for enantioseparation.
Combinations of multiple drugs are an important approach to maximize the chance for therapeutic success by inhibiting multiple pathways/targets. Analytic methods for studying drug combinations have ...received increasing attention because major advances in biomédical research have made available large number of potential agents for testing. The preclinical experiment on multi-drug combinations plays a key role in (especially cancer) drug development because of the complex nature of the disease, the need to reduce development time and costs. Despite recent progresses in statistical methods for assessing drug interaction, there is an acute lack of methods for designing experiments on multi-drug combinations. The number of combinations grows exponentially with the number of drugs and dose-levels and it quickly precludes laboratory testing. Utilizing experimental dose-response data of single drugs and a few combinations along with pathway/network information to obtain an estimate of the functional structure of the dose-response relationship in silico, we propose an optimal design that allows exploration of the dose-effect surface with the smallest possible sample size in this article. The simulation studies show our proposed methods perform well.
Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic ...stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown.
This study explores the potential mechanisms of Xingxiong injection in vivo or in vitro.
Sprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection.
Xingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1β (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression.
Xingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an ...unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs.
Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production.
In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism.
Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.
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