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Oxidized low-density lipoprotein (ox-LDL) causes dysfunction of endothelial progenitor cells (EPCs), and we recently reported that 14-3-3-η can attenuate the damage triggered by ox-LDL in EPCs. However, the molecular mechanisms by which 14-3-3-η protects EPCs from the damage caused by ox-LDL are not fully understood. In this study, we observed that the expression of 14-3-3-η and BCL-2 were downregulated in ox-LDL-treated EPCs. Overexpression of 14-3-3-η in ox-LDL-treated EPC significantly increased BCL-2 level, while knockdown of BCL-2 reduced 14-3-3-η expression and mitigated the protective effect of 14-3-3-η on EPCs. In addition, we discovered that 14-3-3-η colocalizes and interacts with BCL-2 in EPCs. Taken together, these data suggest that 14-3-3-η protects EPCs from ox-LDL-induced damage by its interaction with BCL-2.
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Células Progenitoras Endoteliales , Humanos , Apoptosis , Células Cultivadas , Células Progenitoras Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacología , Lipoproteínas LDL/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
BACKGROUND: Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients' intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients. METHODS: Twenty-six patients with PD and 25 healthy controls (HC) performed a fully-verified event-block design emotional regulation task aimed at investigating responses of implicit cognitive reappraisal during an fMRI scan. Participants passively viewed negatively valanced pictures that were beforehand neutrally, positively, or adversely portrayed in the task. RESULTS: Whole-brain analysis of fMRI data showed that PD patients exhibited less activation in the right dorsolateral prefrontal cortex (dlPFC) and right dorsomedial prefrontal cortex (dmPFC) compared to HC, but presented greater activation in parietal cortex when negative pictures were preceded by positive/neutral vs negative descriptions. Simultaneously, interactive effects of Group × Condition were observed in the right amygdala across both groups. Furthermore, activation in dlPFC and dmPFC was is negatively correlated to severity of anxiety and panic in PD when negative images were preceded by non-negative vs negative descriptions. CONCLUSIONS: Emotional dysregulation in PD is likely the result of deficient activation in dlPFC and dmPFC during implicit cognitive reappraisal, in line with impaired automatic top-down regulation. Correlations between severity of anxiety and panic attack and activation of right dlPFC and dmPFC suggest that the failure to engage prefrontal region during implicit cognitive reappraisal might be associated wtih the severity of anxiety and panic; such functional patterns might be the target of possible treatments.
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Trastorno de Pánico , Mapeo Encefálico , Cognición , Emociones , Humanos , Imagen por Resonancia Magnética , Trastorno de Pánico/complicaciones , Trastorno de Pánico/diagnóstico por imagenRESUMEN
We predict and experimentally observe three-dimensional microscale nonparaxial optical bottle beams based on the generation of a caustic surface under revolution. Such bottle beams exhibit high contrast between the surrounding surface and the effectively void interior. Via caustic engineering, we can precisely control the functional form of the high-intensity surface to achieve microscale bottle beams with longitudinal and transverse dimensions of the same order of magnitude. Although, in general, the phase profile at the input plane can be computed numerically, we find closed-form expressions for bottle beams with various types of surfaces both in the real and in the Fourier space.
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BACKGROUND: Nonketotic hyperglycemia is a rare cause of hemichorea. Patients with hemichorea associated with nonketotic hyperglycemia (HCNH) always have a favorable prognosis when given prompt treatment. METHODS: We reviewed the medical records of 12 patients with HCNH in our hospital between January 2005 and January 2013. The clinical data, laboratory findings, and imaging features of the patients were collected. RESULTS: All 12 patients were admitted to the hospital with a complaint of involuntary movements. Ten patients had a history of diabetes, while the other 2 patients had not been diagnosed. The mean level of blood glucose on admission was 330.7 ± 107.8 mg/dl, and the ketones were negative. A cranial computed tomography scan showed hyperdensity in the striatum, which quickly resolved. Magnetic resonance imaging showed hyperintensity on T1-weighted images without change over several months. Nearly all of the patients experienced relief from the hemichorea symptoms after correcting hyperglycemia with a combination of dopamine receptor inhibitors and the sedative lorazepam, if necessary. CONCLUSION: HCNH is a benign disorder, the pathogenesis of which remains unclear. Radiologic changes can provide guidance for early treatment and generally give an estimation of the degree of injury.
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Corea/patología , Corea/fisiopatología , Hiperglucemia/patología , Hiperglucemia/fisiopatología , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Encéfalo/patología , Corea/complicaciones , Corea/tratamiento farmacológico , Antagonistas de Dopamina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipnóticos y Sedantes/uso terapéutico , Cetonas/sangre , Lorazepam/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Epidural electrical stimulation is a new treatment method for spinal cord injury (SCI). Its efficacy and safety have previously been reported. Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI. Considering that electromyography (EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI, we designed a study protocol for a prospective, randomized controlled trial. In this trial, on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle, patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment. Recovery of muscle strength of key muscles, quality of life, safety and therapeutic effects will be monitored. Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group. The control group will receive conventional rehabilitation treatment. The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment. After rehabilitation treatment, follow up for all patients will occur at 2 weeks and 1, 3 and 6 months. The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale. Secondary outcome measures will include modified Barthel Index scores, integrated EMG values, the visual analogue scale, Spinal Cord Independence Measure scores, and modified Ashworth scale scores. The safety indicator will be the incidence of adverse events. This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment. Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation. This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital (Approval No. RKIRB2022-12) on February 15, 2022 and was registered with Chinese Clinical Trial Registry (registration number: ChiCTR2200061674; date: June 30, 2022). Study protocol version: 1.0.
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BACKGROUND: This paper describes the design and test of an automated functional electrical stimulation (FES) system for poststroke rehabilitation training. The aim of automated FES is to synchronize electrically induced movements to assist residual movements of patients. METHODS: In the design of the FES system, an accelerometry module detected movement initiation and movement performed by post-stroke patients. The desired movement was displayed in visual game module. Synergy-based FES patterns were formulated using a normal pattern of muscle synergies from a healthy subject. Experiment 1 evaluated how different levels of trigger threshold or timing affected the variability of compound movements for forward reaching (FR) and lateral reaching (LR). Experiment 2 explored the effect of FES duration on compound movements. RESULTS: Synchronizing FES-assisted movements with residual voluntary movements produced more consistent compound movements. Matching the duration of synergy-based FES to that of patients could assist slower movements of patients with reduced RMS errors. CONCLUSIONS: Evidence indicated that synchronization and matching duration with residual voluntary movements of patients could improve the consistency of FES assisted movements. Automated FES training can reduce the burden of therapists to monitor the training process, which may encourage patients to complete the training.
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Terapia por Estimulación Eléctrica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Eléctrica , Humanos , Recuperación de la Función , Accidente Cerebrovascular/complicaciones , Extremidad SuperiorRESUMEN
Previous studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury reains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by pIL-35 pretreatment. Moreover, pIL-35 pretreatment significantly decreased the levels of cardiac proinflammatory cytokines including TNF-α, IL-6, and IL-1ß, and the NLRP3 inflammasome. Furthermore, decreased number of apoptotic myocardial cells, increased BCL-2 levels and decreased BAX levels inhibited apoptosis, and LPS-induced upregulation of the expression of cardiac pro-fibrotic genes (MMP2 and MMP9) and fibrotic factor (Collagen type I) was inhibited. Further investigation indicated that pIL-35 pretreatment might suppressed the activation of the cardiac NF-κBp65 and TGF-ß1/Smad2/3 signaling pathways in LPS-treated mice. Similar cardioprotective effects of IL-35 pretreatment were observed in mouse myocardial fibroblasts challenged with LPS in vitro. In summary, IL-35 pretreatment can attenuate cardiac inflammation, apoptosis, and fibrotic reactions induced by LPS, implicating IL-35 as a promising therapeutic target in sepsis-related cardiac injury.
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Lesiones Cardíacas/tratamiento farmacológico , Interleucinas/metabolismo , Interleucinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Lesiones Cardíacas/inducido químicamente , Lesiones Cardíacas/patología , Inflamasomas/metabolismo , Inflamación/tratamiento farmacológico , Interleucinas/uso terapéutico , Lipopolisacáridos/toxicidad , Masculino , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocardio/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico , Sepsis/patología , Transducción de Señal , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Transcripción ReIA/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Objective: To investigate the effects of low frequency transcranial magnetic stimulation (LF-rTMS) combined with motor imagery (MI) on upper limb motor function during stroke rehabilitation. Background: Hemiplegic upper extremity activity obstacle is a common movement disorder after stroke. Compared with a single intervention, sequential protocol or combination of several techniques has been proven to be better for alleviating motor function disorder. Non-invasive neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) have been verified to augment the efficacy of rehabilitation. Methods:Participants were randomly assigned to 2 intervention cohorts: (1) experimental group (rTMS+MI group) was applied at 1 Hz rTMS over the primary motor cortex of the contralesional hemisphere combined with audio-based MI; (2) control group (rTMS group) received the same therapeutic parameters of rTMS combined with audiotape-led relaxation. LF-rTMS protocol was conducted in 10 sessions over 2 weeks for 30 min. Functional measurements include Wolf Motor Function Test (WMFT), the Fugl-Meyer Assessment Upper Extremity (UE-FMA) subscore, the Box and Block Test (BBT), and the Modified Barthel index (MBI) were conducted at baseline, the second week (week 2) and the fourth week (week 4). Results: All assessments of upper limb function improved in both groups at weeks 2 and 4. In particular, significant differences were observed between two groups at end-intervention and after intervention (p < 0.05). In these findings, we saw greater changes of WMFT (p < 0.01), UE-FMA (p < 0.01), BBT (p < 0.01), and MBI (p < 0.001) scores in the experimental group. Conclusions: LF-rTMS combined with MI had a positive effect on motor function of upper limb and can be used for the rehabilitation of upper extremity motor recovery in stroke patients.
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The importance of reappraising negative events to reduce negative emotional responses has been widely acknowledged. However, most neuroimaging studies have explored the neural mechanisms of deliberate and intentional reappraisal, while little is known about the neural correlates of reappraisal that occurs outside of one's awareness. Electrophysiological studies suggest that precedent neutral descriptions could implicitly reduce neural responses to unpleasant images. To investigate the neural mechanism underlying implicit reappraisal, functional magnetic resonance imaging was conducted on 25 participants while they passively viewed unpleasant images that were previously neutrally/positively or negatively described. Increased activity in prefrontal areas including the dorsolateral and dorsomedial prefrontal cortices, lateral orbitofrontal cortex, and temporal cortex, and decreased activation in the amygdala was observed-similar to the pattern reported in deliberate emotion regulation-when unpleasant images were preceded by neutral/positive versus negative descriptions. Functional connectivity analysis revealed significant negative couplings between prefrontal regions and the amygdala. These findings suggest that implicit reappraisal recruits prefrontal regions to change semantic representations in the temporal cortex, in turn modulating the emotional response of the amygdala.