Πέμπτη 7 Απριλίου 2022

Gait Phase Subdivision and Leg Stiffness Estimation During Stair Climbing

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Leg stiffness is considered a prevalent parameter used in data analysis of leg locomotion during different gaits, such as walking, running, and hopping. Quantification of the change in support leg stiffness during stair ascent and descent will enhance our understanding of complex stair climbing gait dynamics. The purpose of this study is to investigate a methodology to estimate leg stiffness during stair climbing and subdivide the stair climbing gait cycle. Leg stiffness was determined as the ratio of changes in ground reac tion force in the direction of the support leg ${F}_{l}$ (leg force) to the respective changes in length ${L}_{l}$ during the entire stance phase. Eight subjects ascended and descended an instrumented staircase at different cadences. In this study, the changes of leg force and length (force–length curve) are described as the leg stiffness curve, the slope of which represents the normalized stiffness during stair climbing. The stair ascent and descent gait cycles were subdivided based on the negative and positive work fluctuations of the center-of-mass (CoM) work rate curve and the characteristics of leg stiffness. We found that the leg stiffness curve consists of several segments in which the force–length relationship was similarly linear and the stiffness value was relatively constant; the phase divided by the leg stiffness curve corresponds to the phase divided by the CoM work rate curve. The results of this study may guide biomimetic control strategies for a wearable lowe r-extremity robot for the entire stance phase during stair climbing.
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Study on the Effects of Different Seat and Leg Support Conditions of a Trunk Rehabilitation Robot

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Performance of trunk rehabilitation exercises while sitting on movable surfaces with feet on the ground can increase trunk and leg muscle activations, and constraining the feet to move with the seat isolates control of the trunk. However, there are no detailed studies on the effects of these different leg supports on the trunk and leg muscle activations under unstable and forcefully perturbed seating conditions. We have recently devised a trunk rehabilitation robot that can generate unstable and forcefully perturbed sitting surfaces, and can be used with ground-mounted or seat-connected footrests. In this study, we have evaluated the differences in balance performance, trunk movement and muscle activation (trunk and legs) of fourteen healthy adults caused by the use of these different footrest configurations under the different seating scenarios. The center of pressure and trunk movement results show that the seat-connected footrest may be a more suitable choice for use in a balance recovery focused rehabilitation protocol, while the ground-mounted footrest may be a more suitable choice for a trunk movement focused rehabilitation protocol. Although it is difficult to make a clear selection between footrests due to the mixed trends observed in the muscle activation results, it appears that the seat-connected footrest may be preferable for use with the unstable seat as it causes greater muscle activations. Furthermore, the results provide limited evidence that targeting of a particular muscle group may be possible through careful selection of the seat and footrest conditions. Therefore, it may be possible to utilize the trunk rehabilitation robot to maximize the training outcomes for a wide range of patients through careful selection of training protocols.
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Outcomes of Cervical Disc Replacement in Patients With Neck Pain Greater Than Arm Pain

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Although anterior cervical discectomy and fusion (ACDF) is believed to positively impact a patient's radicular symptoms as well as axial neck pain, the outcomes of cervical disc replacement (CDR) with regards to neck pain specifically have not been established.
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miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot

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Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.
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Glycyrrhizin Attenuates Hypoxic-Ischemic Brain Damage by Inhibiting Ferroptosis and Neuroinflammation in Neonatal Rats via the HMGB1/GPX4 Pathway

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With unknown etiology and limited treatment options, neonatal hypoxic-ischemic brain damage (HIBD) remains a major cause of mortality in newborns. Ferroptosis, a recently discovered type of cell death triggered by lipid peroxidation, is closely associated with HIBD. High-mobility group box 1 (HMGB1), a molecule associated with inflammation damage, can induce neuronal death in HIBD. However, it remains unknown whether HMGB1 contributes to neuronal ferroptosis in patients with HIBD. Herein, glycyrrhizin (GL), an HMGB1 inhibitor, was used to investigate the relationship between ferroptosis and HMGB1. RAS-selective lethal 3(RSL3), a ferroptosis agonist, was administered to further confirm the changes in the signaling pathway between HMGB1 and ferroptosis. Western blot analysis revealed that GL mar kedly suppressed the expression of HMGB1 and increased the level of GPX4 in the context of HIBD. We observed changes in neuronal ultrastructure via transmission electron microscopy to further confirm the occurrence of ferroptosis. Real-time PCR indicated that GL inhibited the expression of ferroptosis-related genes and inflammatory factors. Immunofluorescence and immunohistochemistry staining confirmed GL inhibition of neuronal damage and ferroptosis in HIBD associated with GPX4 and ROS. GL not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by HIBD in vivo. More importantly, GL may improve oxidative stress imbalance and mitochondrial damage, alleviate the downstream production of inflammatory factors, and ultimately reduce ferroptosis and damage to cortical neurons following HIBD via the HMGB1/GPX4 pathway. In conclusion, we showed for the first time that GL could suppress the occurrence of neuronal ferroptos is and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. These findings highlight the potential of HMGB1 signaling antagonists to treat neuronal damage by suppressing ferroptosis, provide new and unique insights into GL as a neuroprotective agent, and suggest new prevention and treatment strategies for HIBD.
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Integrated Network Pharmacology and Gut Microbiota Study on the Mechanism of Huangqin Decoction in Treatment Diabetic Enteritis

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Objective. Using network pharmacology and gut microbiota sequencing to investigate the probable mechanism of Huangqin decoction in the treatment of Diabetic enteritis (DE). Methods. The mechanism of Huangqin decoction on DE was studied by combining network pharmacology and gut microbiota sequencing analysis. The core components and possible targets of Huangqin decoction were analyzed by network pharmacology. The effect of Huangqin decoction on microorganisms was investigated by gut microbiota sequencing. Results. The results of gut microbiota sequencing analysis showed the abundance of TM7, Tenericutes, Chloroflexi, Cyanobacteria, Acidobacteria, WS6, [Prevotella], Helicobacter, Prevotella, Lactococcus, and Anaeroplasma in the Huangqin decoction group had a significant downward. Using a network ph armacology-related database, 141 main active components of Huangqin decoction were identified, as well as 256 corresponding component targets and 1777 corresponding disease targets; the disease targets and component targets were mapped, and topological analysis was used to determine the potential of Huangqin decoction in the treatment of DE. There were 156 targets, of which the top 20 genes were selected for GO and KEGG. The KEGG results showed that 134 pathways were enriched, which was partially consistent with the metabolic pathways of gut microbiota sequencing analysis. Conclusion. The results show that Huangqin decoction can inhibit the expression of inflammatory factors and related inflammatory pathways in intestinal epithelial cells, thereby regulating the structure of intestinal flora. Using picurst2 for functional prediction and metabolic pathway statistics, seven metabolic pathways were obtained consistent with gut microbiota sequencing, and the NOD-like receptor signaling pathway may be its potential molecular mechanism. These results help to understand the mechanism of Huangqin decoction on DE and provide the theoretical basis for further study of Huangqin decoction.
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Optimized Protocol for the Isolation of Extracellular Vesicles from the Parasitic Worm Schistosoma mansoni with Improved Purity, Concentration, and Yield

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In the past decade, the interest in helminth-derived extracellular vesicles (EVs) increased owing to their role in pathogen-host communication. However, the availability of EVs from these parasitic worms is often limited due to the restricted occurrence and culturing possibilities of these organisms. Schistosoma mansoni is one of several helminths that have been shown to release EVs affecting the immune response of their host. Further investigation of mechanisms underlying these EV-induced effects warrants separation of EVs from other components of the helminth excretory/secretory products. However, isolation of high-purity EVs often come to the expense of reduced EV yield. We therefore aimed to develop an optimized protocol for isolation of EVs from S. mansoni schistosomula and adult worms with respect to purity, concentration, and yield. We tested the use of small (1.7 ml) iodixanol density gradients and demonstrated that this enabled western blot-based analysis of the EV marker protein tetraspanin-2 (TSP-2) in gradient fractions without additional concentration steps. Moreover, the concentration and yield of EVs obtained with small iodixanol gradients were higher compared to medium-sized (4.3 ml) or conventional large-sized (12 ml) gradients. Additionally, we provide evidence that iodixanol is preferred over sucrose as medium for the small density gradients, because EVs in iodixanol gradients reached equilibrium much faster (2 hours) and iodixanol but not sucrose was suitable for purification of schistosomula EVs. Finally, we demonstrate that the small iodixanol gradients were able to separate adult worm EVs from non-EV contaminants such as the blood digestion product hemozoin. Our optimized small iodixanol density gradient allows to simultaneously separate and con centrate EVs while reducing handling time and EV loss and can be applied for EVs from helminths and other limited EV sources.
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