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1.
Nat Immunol ; 16(11): 1142-52, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26414765

RESUMEN

Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.


Asunto(s)
Fagocitos/inmunología , Fagocitos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Infecciones Bacterianas/etiología , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/metabolismo , Actividad Bactericida de la Sangre/inmunología , Línea Celular , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Antígenos de Histocompatibilidad Menor , Mitocondrias/inmunología , Mitocondrias/metabolismo , Mitocondrias/microbiología , Fagocitos/microbiología , Fagosomas/inmunología , Fagosomas/metabolismo , Fagosomas/microbiología , Proteína Quinasa C-alfa/metabolismo , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Sepsis/etiología , Sepsis/inmunología , Sepsis/metabolismo , Serina-Treonina Quinasa 3 , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Receptores Toll-Like/metabolismo , Ubiquitinación , Proteínas de Unión al GTP rac/genética , Proteínas de Unión al GTP rac/metabolismo , Inhibidor beta de Disociación del Nucleótido Guanina rho/metabolismo
2.
J Immunol ; 212(3): 397-409, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38088801

RESUMEN

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.


Asunto(s)
Coriomeningitis Linfocítica , Virus de la Coriomeningitis Linfocítica , Animales , Ratones , Linfocitos T CD8-positivos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Muerte Celular Programada 1/metabolismo , Agotamiento de Células T
3.
Pharmacol Res ; 207: 107301, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39009291

RESUMEN

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

4.
J Biol Chem ; 298(11): 102599, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36244448

RESUMEN

Mutations in the hyperpolarization-activated nucleotide-gated channel 4 (HCN4) are known to be associated with arrhythmias in which QT prolongation (delayed ventricular repolarization) is rare. Here, we identified a HCN4 mutation, HCN4-R666Q, in two sporadic arrhythmia patients with sinus bradycardia, QT prolongation, and short bursts of ventricular tachycardia. To determine the functional effect of the mutation, we conducted clinical, genetic, and functional analyses using whole-cell voltage-clamp, qPCR, Western blot, confocal microscopy, and co-immunoprecipitation. The mean current density of HEK293T cells transfected with HCN4-R666Q was lower in 24 to 36 h after transfection and was much lower in 36 to 48 h after transfection relative to cells transfected with wildtype HCN4. Additionally, we determined that the HCN4-R666Q mutant was more susceptible to ubiquitin-proteasome system-mediated protein degradation than wildtype HCN4. This decreased current density for HCN4-R666Q could be partly rescued by treatment with a proteasome inhibitor. Therefore, we conclude that HCN4-R666Q had an effect on HCN4 function in two aspects, including decreasing the current density of the channel as a biophysical effect and weakening its protein stability. Our findings provide new insights into the pathogenesis of the HCN4-R666Q mutation.


Asunto(s)
Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Síndrome de QT Prolongado , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Canales de Potasio/metabolismo , Proteolisis , Nucleótidos/metabolismo , Células HEK293 , Proteínas Musculares/metabolismo , Arritmias Cardíacas/genética , Mutación , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética
5.
Photosynth Res ; 158(2): 81-90, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36847892

RESUMEN

Gloeobacter violaceus is an ancient cyanobacterium as it branches out from the basal position in the phylogenic tree of cyanobacteria. It lacks thylakoid membranes and its unique bundle-shaped type of phycobilisomes (PBS) for light harvesting in photosynthesis are located on the interior side of cytoplasmic membranes. The PBS from G. violaceus have two large linker proteins that are not present in any other PBS, Glr2806, and Glr1262, which are encoded by the genes glr2806 and glr1262, respectively. The location and functions of the linkers Glr2806 and Glr1262 are currently unclear. Here, we report the studies of mutagenetic analysis of glr2806 and the genes of cpeBA, encoding the ß and α subunits of phycoerythrin (PE), respectively. In the mutant lacking glr2806, the length of the PBS rods remains unchanged, but the bundles are less tightly packed as examined by electron microscopy with negative staining. It is also shown that two hexamers are missing in the peripheral area of the PBS core, strongly suggesting that the linker Glr2806 is located in the core area instead of the rods. In the mutant lacking the cpeBA genes, PE is no longer present and the PBS rods have only three layers of phycocyanin hexamers. The construction of deletional mutants in G. violaceus, achieved for the first time, provides critical information for our understanding of its unique PBS and should be useful in studies of other aspects of this interesting organism as well.


Asunto(s)
Cianobacterias , Ficobilisomas , Ficobilisomas/metabolismo , Mutágenos/metabolismo , Proteínas/metabolismo , Cianobacterias/genética , Cianobacterias/metabolismo , Ficocianina/metabolismo , Ficoeritrina/metabolismo
6.
Chemistry ; 29(48): e202301121, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37300353

RESUMEN

Lithium-sulfur (Li-S) batteries are a promising energy storage technology due to their tempting high theoretical capacity and energy density. Nevertheless, the wastage of active materials that originates from the shuttling effect of polysulfides still hinders advancement of Li-S batteries. The effective design of cathode materials is extremely pivotal to solve this thorny problem. Herein, surface engineering in covalent organic polymers (COPs) has been performed to investigate the influence of pore wall polarity on the performance of COP-based cathodes used for Li-S batteries. With the assistance of experimental investigation and theoretical calculations, performance improvement by increasing pore surface polarity and a synergy effect of the polarized functionalities, along with nano-confinement effect of the COPs, are disclosed, to which the improved performance of Li-S batteries including outstanding Coulombic efficiency (99.0 %) and extremely low capacity decay (0.08 % over 425 cycles at 1.0 C) is attributed. This work not only enlightens the designable synthesis and applications of covalent polymers as polar sulfur hosts with high utilization of active materials, but also provides a feasible guide for the design of effective cathode materials for future advanced Li-S batteries.

8.
Appl Microbiol Biotechnol ; 107(7-8): 2639-2651, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36810625

RESUMEN

Protein purification is a basic technology in both biological research and industrial production, and efficient, convenient, economical, and environmentally friendly purification methods have always been pursued. In this study, it was found that alkaline earth metal cations (Mg2+, Ca2+) and alkali metal cations (Li+, Na+, K+) and even nonmetal cations (e.g., NH4+, imidazole, guanidine, arginine, lysine) can precipitate multi-histidine-tagged proteins (at least two tags in a whole protein) at low salts concentrations that are 1-3 orders of magnitude lower than salting-out, and precipitated proteins could be dissolved at moderate concentration of corresponding cation. Based on this finding, a novel cation affinity purification method was developed, which requires only three centrifugal separations to obtain highly purified protein with purification fold similar to that of immobilized metal affinity chromatography. The study also provides a possible explanation for unexpected protein precipitation and reminds researchers to consider the influence of cations on the experimental results. The interaction between histidine-tagged proteins and cations may also have broad application prospects. KEY POINTS: • Histidine-tagged proteins can be precipitated by low-concentrations common cations • A novel nonchromatographic protein purification method was developed • Purified protein can be obtained in pellet form by only three centrifugations.


Asunto(s)
Histidina , Histidina/química , Histidina/metabolismo , Indicadores y Reactivos , Cationes , Cromatografía de Afinidad/métodos , Proteínas Recombinantes
9.
Phytother Res ; 37(4): 1422-1434, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36737044

RESUMEN

The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%-21.89% and 16.29%-22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.


Asunto(s)
Lignanos , Vitex , Ratas , Animales , Osteoclastos , Vitex/metabolismo , Actinas/metabolismo , Linfocitos T , Lignanos/farmacología , Diferenciación Celular
10.
Nano Lett ; 22(23): 9685-9692, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36441867

RESUMEN

The practical application of Na-superionic conductor structured materials is hindered by limited energy density and structure damage upon activating the third Na+. We propose a bimetal substitution strategy with cheaper Fe and Ni elements for costive vanadium in the polyanion to improve both ionic and electronic conductivities, and a single two-phase reaction during Na+ intercalation/deintercalation and much reduced Na+ diffusion barrier are uncovered by ex-situ X-ray diffraction and density functional theory calculations. Thus, the obtained cathode, Na3Fe0.8VNi0.2(PO4)3, shows excellent electrochemical performances including high specific capacity (102.2 mAh g-1 at 0.1C), excellent rate capability (79.3 mAh g-1 at 20C), cycling stability (84.6% of capacity retention over 1400 cycles at 20C), low-temperature performance (89.7 mAh g-1 at 2C and -10 °C), and structure stability in an extended voltage window for the third Na+ utilization. A competitive energy density of ≈287 Wh kg-1 for full batteries based on cathode and anode materials is also confirmed.

11.
J Proteome Res ; 21(2): 507-518, 2022 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-34969243

RESUMEN

Targeted analysis of data-independent acquisition (DIA) data needs a spectral library, which is generated by data-dependent acquisition (DDA) experiments or directly from DIA data. A comparison of the DDA library and DIA library in analyzing DIA data has been reported. However, the effects of different spectral libraries on the analysis of diaPASEF data have not been investigated. Here, we generate different spectral libraries with varying proteome coverage to analyze parallel accumulation-serial fragmentation (diaPASEF) data. Besides, we also employ the library-free strategy. The library, constructed by extensive fractionation DDA experiments, produces the highest numbers of precursors and proteins but with a high percentage of missing values. The library-free strategy identifies 10-20% fewer proteins than the library-based method but with a high degree of data completeness. A further study shows that the library-free strategy, although it identifies fewer proteins than the library-based method, leads to similar biological conclusions as the library-based method.


Asunto(s)
Proteoma , Proteómica , Biblioteca de Péptidos , Proteómica/métodos
12.
Ecotoxicol Environ Saf ; 237: 113557, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35483149

RESUMEN

Mounting evidence has confirmed the existence of plant-soil feedback, a reflection of plant-soil interaction. However, analysis of ecological feedback pathways remains a challenge. In this study, single and mixed plant communities in different soil ecosystems were screened using strict control systems in global ecosystems to identify the positive or negative feedback effects in indicator plants. Furthermore, the plant components and biomass were identified in each pathway. The significantly changed components indicated pathway factors. As negative feedback increased, the InRR (Response Ratio) of soil organic matter, soil total N, microbial alpha diversity and the symbiotic fungi proportion were significantly up-regulated (P < 0.05). In contrast, the stoichiometric ratio (C: N), water content, and the pathogenic bacteria proportion were downregulated (P < 0.05). However, the positive feedback showed the opposite trend. Importantly, N limit as a transform node between positive and negative plant-soil feedback predicted by Akaike information criterion (AIC > 0.8). Therefore, it has become an important evaluation standard for the inter-species relationship and ecological environment changes under the background of global N deposition. Finally, the feedback values of each sampling site were recalculated over the next 20 years, 50 years, and 100 years based on the global temperature rise and changing rainfall patterns. We also found that global warming and extreme rainfall may change the distribution of interspecies relationships on a global scale, with global warming having the greatest recognisable effect and decreasing the negative feedback layout by 21.7% (P < 0.05). Therefore, this work promotes the cognition of relationship of soil environment, microbial abundance and function, plant diversity and plant- soil feedback model. Meanwhile, it is of great significance to protect species diversity and restore environmental degradation.


Asunto(s)
Micorrizas , Suelo , Biodiversidad , Ecosistema , Retroalimentación , Micorrizas/metabolismo , Nitrógeno/análisis , Plantas/metabolismo , Microbiología del Suelo , Temperatura
13.
Entropy (Basel) ; 25(1)2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36673158

RESUMEN

Large-scale industrial processes usually adopt centralized control and optimization methods. However, with the growth of the scale of industrial processes leading to increasing computational complexity, the online optimization capability of the double-layer model predictive control algorithm is challenged, exacerbating the difficulty of the widespread implementation of this algorithm in the industry. This paper proposes a distributed double-layer model predictive control algorithm based on dual decomposition for multivariate constrained systems to reduce the computational complexity of process control. Firstly, to solve the problem that the original dual decomposition method does not apply to constrained systems, two improved dual decomposition model prediction control methods are proposed: the dual decomposition method based on the quadratic programming in the subsystem and the dual decomposition method based on constraint zones, respectively. It is proved that the latter will certainly converge to the constraint boundaries with appropriate convergence factors for the controlled variables. The online optimization ability of the proposed two methods is compared in discussion and simulation, concluding that the dual decomposition method based on the constraint zones exhibits superior online optimization ability. Further, a distributed double-layer model predictive control algorithm with dual decomposition based on constraint zones is proposed. Different from the objective function of the original dual decomposition model predictive control, the proposed algorithm's dynamic control-layer objective function simultaneously tracks the steady-state optimization values of the controlled and manipulated variables, giving the optimal solution formulation of the optimization problem consisting of this objective function and the constraints. The algorithm proposed in this paper achieves the control goals while significantly reducing the computational complexity and has research significance for promoting the industrial implementation of double-layer model predictive control.

14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(4): 721-729, 2022 Aug 25.
Artículo en Zh | MEDLINE | ID: mdl-36008336

RESUMEN

[Abstract]Automatic and accurate segmentation of lung parenchyma is essential for assisted diagnosis of lung cancer. In recent years, researchers in the field of deep learning have proposed a number of improved lung parenchyma segmentation methods based on U-Net. However, the existing segmentation methods ignore the complementary fusion of semantic information in the feature map between different layers and fail to distinguish the importance of different spaces and channels in the feature map. To solve this problem, this paper proposes the double scale parallel attention (DSPA) network (DSPA-Net) architecture, and introduces the DSPA module and the atrous spatial pyramid pooling (ASPP) module in the "encoder-decoder" structure. Among them, the DSPA module aggregates the semantic information of feature maps of different levels while obtaining accurate space and channel information of feature map with the help of cooperative attention (CA). The ASPP module uses multiple parallel convolution kernels with different void rates to obtain feature maps containing multi-scale information under different receptive fields. The two modules address multi-scale information processing in feature maps of different levels and in feature maps of the same level, respectively. We conducted experimental verification on the Kaggle competition dataset. The experimental results prove that the network architecture has obvious advantages compared with the current mainstream segmentation network. The values of dice similarity coefficient (DSC) and intersection on union (IoU) reached 0.972 ± 0.002 and 0.945 ± 0.004, respectively. This paper achieves automatic and accurate segmentation of lung parenchyma and provides a reference for the application of attentional mechanisms and multi-scale information in the field of lung parenchyma segmentation.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(6): 1189-1198, 2022 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-36575089

RESUMEN

Gesture imitation is a common rehabilitation strategy in limb rehabilitation training. In traditional rehabilitation training, patients need to complete training actions under the guidance of rehabilitation physicians. However, due to the limited resources of the hospital, it cannot meet the training and guidance needs of all patients. In this paper, we proposed a following control method based on Kinect and NAO robot for the gesture imitation task in rehabilitation training. The method realized the joint angles mapping from Kinect coordination to NAO robot coordination through inverse kinematics algorithm. Aiming at the deflection angle estimation problem of the elbow joint, a virtual space plane was constructed and realized the accurate estimation of deflection angle. Finally, a comparative experiment for deflection angle of the elbow joint angle was conducted. The experimental results showed that the root mean square error of the angle estimation value of this method in right elbow transverse deflection and vertical deflection directions was 2.734° and 2.159°, respectively. It demonstrates that the method can follow the human movement in real time and stably using the NAO robot to show the rehabilitation training program for patients.


Asunto(s)
Articulación del Codo , Robótica , Rehabilitación de Accidente Cerebrovascular , Humanos , Extremidad Superior , Robótica/métodos , Rehabilitación de Accidente Cerebrovascular/métodos , Modalidades de Fisioterapia , Fenómenos Biomecánicos
16.
FASEB J ; 34(6): 7631-7643, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32301540

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders which are characterized by the accumulation of excessive lipid in hepatocytes. The precise pathogenesis of NAFLD is very complicated and remains largely unknown. Smad ubiquitination regulatory factor 1 (Smurf1) is crucial for numerous processes including bone homeostasis, embryogenesis, and pathogenic autophagy. In this study, we found that liver steatosis was alleviated in Smurf1-deficient mice fed with high-fat diet (HFD) for 19 weeks. The deletion of Smurf1 reduced the accumulation of lipid droplets and triglycerides in hepatocytes. The stability of sterol regulatory element-binding protein-1c (SREBP-1c), a key transcription factor that mediates de novo lipogenesis, was markedly reduced in Smurf1-deficient mice. The mechanistic study showed that Smurf1 interacts with SREBP-1c and protects SREBP-1c from ubiquitination and degradation by preventing the binding of SREBP-1c to its ubiquitin E3 ligase Fbw7a. Thus, our study presented an E3 ligase catalytic activity-independent function of Smurf1 in the fatty liver development.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Células HEK293 , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Lípidos/fisiología , Lipogénesis/fisiología , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transcripción Genética/fisiología , Triglicéridos/metabolismo
17.
Neurochem Res ; 46(2): 349-357, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33211272

RESUMEN

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(-/-) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(-/-) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.


Asunto(s)
MicroARNs/uso terapéutico , Neuralgia/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Regulación hacia Abajo , Técnicas de Inactivación de Genes , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Locomoción/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/metabolismo , Mitocondrias/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Neuralgia/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismo
18.
J Neuroeng Rehabil ; 18(1): 74, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947410

RESUMEN

BACKGROUND: The key challenge to constructing functional corticomuscular coupling (FCMC) is to accurately identify the direction and strength of the information flow between scalp electroencephalography (EEG) and surface electromyography (SEMG). Traditional TE and TDMI methods have difficulty in identifying the information interaction for short time series as they tend to rely on long and stable data, so we propose a time-delayed maximal information coefficient (TDMIC) method. With this method, we aim to investigate the directional specificity of bidirectional total and nonlinear information flow on FCMC, and to explore the neural mechanisms underlying motor dysfunction in stroke patients. METHODS: We introduced a time-delayed parameter in the maximal information coefficient to capture the direction of information interaction between two time series. We employed the linear and non-linear system model based on short data to verify the validity of our algorithm. We then used the TDMIC method to study the characteristics of total and nonlinear information flow in FCMC during a dorsiflexion task for healthy controls and stroke patients. RESULTS: The simulation results showed that the TDMIC method can better detect the direction of information interaction compared with TE and TDMI methods. For healthy controls, the beta band (14-30 Hz) had higher information flow in FCMC than the gamma band (31-45 Hz). Furthermore, the beta-band total and nonlinear information flow in the descending direction (EEG to EMG) was significantly higher than that in the ascending direction (EMG to EEG), whereas in the gamma band the ascending direction had significantly higher information flow than the descending direction. Additionally, we found that the strong bidirectional information flow mainly acted on Cz, C3, CP3, P3 and CPz. Compared to controls, both the beta-and gamma-band bidirectional total and nonlinear information flows of the stroke group were significantly weaker. There is no significant difference in the direction of beta- and gamma-band information flow in stroke group. CONCLUSIONS: The proposed method could effectively identify the information interaction between short time series. According to our experiment, the beta band mainly passes downward motor control information while the gamma band features upward sensory feedback information delivery. Our observation demonstrate that the center and contralateral sensorimotor cortex play a major role in lower limb motor control. The study further demonstrates that brain damage caused by stroke disrupts the bidirectional information interaction between cortex and effector muscles in the sensorimotor system, leading to motor dysfunction.


Asunto(s)
Algoritmos , Electroencefalografía/métodos , Electromiografía/métodos , Accidente Cerebrovascular/fisiopatología , Interfaz Usuario-Computador , Anciano , Simulación por Computador , Retroalimentación Sensorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiología , Músculo Esquelético/fisiología , Proyectos Piloto
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1154-1162, 2021 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-34970899

RESUMEN

The functional coupling between motor cortex and effector muscles during autonomic movement can be quantified by calculating the coupling between electroencephalogram (EEG) signal and surface electromyography (sEMG) signal. The maximal information coefficient (MIC) algorithm has been proved to be effective in quantifying the coupling relationship between neural signals, but it also has the problem of time-consuming calculations in actual use. To solve this problem, an improved MIC algorithm was proposed based on the efficient clustering characteristics of K-means ++ algorithm to accurately detect the coupling strength between nonlinear time series. Simulation results showed that the improved MIC algorithm proposed in this paper can capture the coupling relationship between nonlinear time series quickly and accurately under different noise levels. The results of right dorsiflexion experiments in stroke patients showed that the improved method could accurately capture the coupling strength of EEG signal and sEMG signal in the specific frequency band. Compared with the healthy controls, the functional corticomuscular coupling (FCMC) in beta (14~30 Hz) and gamma band (31~45 Hz) were significantly weaker in stroke patients, and the beta-band MIC values were positively correlated with the Fugl-Meyers assessment (FMA) scale scores. The method proposed in this study is hopeful to be a new method for quantitative assessment of motor function for stroke patients.


Asunto(s)
Corteza Motora , Accidente Cerebrovascular , Algoritmos , Electroencefalografía , Electromiografía , Humanos , Músculo Esquelético
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 65-71, 2021 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-33899429

RESUMEN

Early accurate detection of inferior myocardial infarction is an important way to reduce the mortality from inferior myocardial infarction. Regrading the existing problems in the detection of inferior myocardial infarction, complex model structures and redundant features, this paper proposed a novel inferior myocardial infarction detection algorithm. Firstly, based on the clinic pathological information, the peak and area features of QRS and ST-T wavebands as well as the slope feature of ST waveband were extracted from electrocardiogram (ECG) signals leads Ⅱ, Ⅲ and aVF. In addition, according to individual features and the dispersion between them, we applied genetic algorithm to make judgement and then input the feature with larger degree into support vector machine (SVM) to realize the accurate detection of inferior myocardial infarction. The proposed method in this paper was verified by Physikalisch-Technische Bundesanstalt (PTB) diagnostic electrocardio signal database and the accuracy rate was up to 98.33%. Conforming to the clinical diagnosis and the characteristics of specific changes in inferior myocardial infarction ECG signal, the proposed method can effectively make precise detection of inferior myocardial infarction by morphological features, and therefore is suitable to be applied in portable devices development for clinical promotion.


Asunto(s)
Infarto de la Pared Inferior del Miocardio , Algoritmos , Bases de Datos Factuales , Electrocardiografía , Humanos , Máquina de Vectores de Soporte
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