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Cryo-electron microscopy (cryo-EM) has emerged as a potent technique for determining the structure and functionality of biological macromolecules. However, limited by the physical imaging conditions, such as low electron beam dose, micrographs in cryo-EM typically contend with an extremely low signal-to-noise ratio (SNR), impeding the efficiency and efficacy of subsequent analyses. Therefore, there is a growing demand for an efficient denoising algorithm designed for cryo-EM micrographs, aiming to enhance the quality of macromolecular analysis. However, owing to the absence of a comprehensive and well-defined dataset with ground truth images, supervised image denoising methods exhibit limited generalization when applied to experimental micrographs. To tackle this challenge, we introduce a simulation-aware image denoising (SaID) pretrained model designed to enhance the SNR of cryo-EM micrographs where the training is solely based on an accurately simulated dataset. First, we propose a parameter calibration algorithm for simulated dataset generation, aiming to align simulation parameters with those of experimental micrographs. Second, leveraging the accurately simulated dataset, we propose to train a deep general denoising model that can well generalize to real experimental cryo-EM micrographs. Comprehensive experimental results demonstrate that our pretrained denoising model achieves excellent denoising performance on experimental cryo-EM micrographs, significantly streamlining downstream analysis.
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Algoritmos , Microscopía por Crioelectrón , Procesamiento de Imagen Asistido por Computador , Relación Señal-Ruido , Microscopía por Crioelectrón/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Simulación por ComputadorRESUMEN
BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).
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Interfaces Cerebro-Computador , Accidente Cerebrovascular Isquémico , Rehabilitación de Accidente Cerebrovascular , Extremidad Superior , Humanos , Masculino , Rehabilitación de Accidente Cerebrovascular/métodos , Femenino , Persona de Mediana Edad , Extremidad Superior/fisiopatología , Accidente Cerebrovascular Isquémico/rehabilitación , Accidente Cerebrovascular Isquémico/fisiopatología , Anciano , China , Recuperación de la Función/fisiología , Resultado del Tratamiento , AdultoRESUMEN
Fiducial marker detection in electron micrographs becomes an important and challenging task with the development of large-field electron microscopy. The fiducial marker detection plays an important role in several steps during the process of electron micrographs, such as the alignment and parameter calibrations. However, limited by the conditions of low signal-to-noise ratio (SNR) in the electron micrographs, the performance of fiducial marker detection is severely affected. In this work, we propose the MarkerDetector, a novel algorithm for detecting fiducial markers in electron micrographs. The proposed MarkerDetector is built upon the following contributions: Firstly, a wavelet-based template generation algorithm is devised in MarkerDetector. By adopting a shape-based criterion, a high-quality template can be obtained. Secondly, a robust marker determination strategy is devised by utilizing statistic-based filtering, which can guarantee the correctness of the detected fiducial markers. The average running time of our algorithm is 1.67 seconds with promising accuracy, indicating its practical feasibility for applications in electron micrographs.
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Electrones , Marcadores Fiduciales , Algoritmos , MicroscopíaRESUMEN
A high power and high quality picosecond laser is crucial in MEMS fabrication regarding micromachines. Optimal seed beam coupling is an important precondition to enhance laser efficiency. However, empirical coupling limits its development. In this paper, the physical parameters related to coupling are determined. The relationships among them are established under optical mode matching constraints to satisfy optimal seed beam coupling. According to a theoretical analysis, the focal length cut-off and the optimal coupling position of the coupling lens are acquired. A maximum transmittance of 87.2% is acquired with a 6 W input seed power in the validation experiment. In further power amplification experiments, a diffraction-limited beam quality is achieved, with M2X = 1.111, M2Y = 1.017, an optical efficiency of 60.5% and a slope efficiency of 66%, benefiting from the previous theoretical guidance.
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Objectives: To observe the efficacy of botulinum toxin type A (BoNT-A) for the spasticity of the lower-limb post-stroke on gait and posture control. Methods: A total of 46 patients with hemiplegia gait were randomly divided into the experimental group (23 patients) and the control group (23 patients). In patients in the experimental group received injections of BoNT-A by electrical stimulation-guided. At the same time, patients of the two groups received routine physical therapy. Gait analysis, plantar pressure analysis, lower-limb Fugl-Meyer assessment (L-FMA), 10 meter walking test (10MWT), timed "Up and Go" test (TUGT), and modified Ashworth Scale assess (MAS) of the lower limbs were performed at 0, 1, 4, and 12 weeks after treatment. Results: At 1, 4, and 12 weeks after treatment, the L-FMA, stride length, speed, and TUGT significantly improved than 0 week in both groups. The L-FMA and peak of forefoot pressure, and MAS results in the experimental group were better than those in the control group at 4 and 12 weeks. The TUGT, speed, and stride length in experimental group was significantly shortened than that in control group at 1, 4, and 12 weeks. Conclusion: Botulinum toxin type A injection can improve motor functions of the lower limb, gait, spasticity, forefoot pressure, and posture control of patients after stroke.
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Apocynin (4-hydroxy-3-methoxyacetophenone) is a natural polyphenolic compound with multiple biological activities. In the present study, a series of apocynin derivatives were designed and synthesized. The in silico ADMET prediction, blood-brain barrier (BBB) penetration assay, anti-NADPH oxidase activity, reactive oxygen species (ROS) levels, and anti-glioma effects of these apocynin derivatives were evaluated. The anti-glioma mechanisms of candidate compounds were studied by ï¬ow cytometer and Western blot. The results showed that D31 exhibited higher BBB penetration, increased ROS generations and significant anti-glioma effects both in vitro and in vivo. Further studies showed that D31 inhibited the activations of NF-κB pathway. Overall, our data demonstrated that D31 inhibited growth and induced apoptosis of glioma, which might be caused by ROS-related NF-κB activation. The current study suggested that D31 could be further explored for its potential use in anti-glioma therapy.
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[This corrects the article DOI: 10.3389/fnagi.2018.00227.].
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Objective: Recent studies have suggested that metformin can penetrate the blood-brain barrier, protecting neurons via anti-inflammatory action and improvement of brain energy metabolism. In this study, we aim to investigate the effect of metformin on cognitive function in patients with abnormal glucose metabolism and non-dementia vascular cognitive impairment (NDVCI). Methods: One hundred patients with NDVCI and abnormal glucose metabolism were randomly allocated into two groups: metformin and donepezil (n = 50) or acarbose and donepezil (n = 50). The neuropsychological status, glucose metabolism, and common carotid arteries intima-media thickness (CCA-IMT) before and after a year of treatment, were measured and compared between the groups. Results: Ninety four patients completed all the assessment and follow-up. After a year of treatment, there was a decrease in Alzheimer's disease Assessment Scale-Cognitive Subscale scores and the duration of the Trail Making Test in the metformin-donepezil group. Furthermore, these patients showed a significant increase in World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test scores after treatment (all P < 0.05). However, there was no obvious improvement in cognitive function in the acarbose-donepezil group. We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P < 0.05). Conclusion: We conclude that metformin can improve cognitive function in patients with NDVCI and abnormal glucose metabolism, especially in terms of performance function. Improved cognitive function may be related to improvement of IR and the attenuated progression of IMT. Trial Registration: ChiCTR-IPR-17011855.
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The four kinds of adenosine receptor subtypes (ARs), named as ARA1, ARA2A, ARA2B and ARA3, have multiple biological functions. ARs are differently distributed across the body and have distinguished ability of binding adenosine. We try to figure out how these ARs were expressed in astrocytes and which one has the first priority of utilizing adenosine. Firstly, mRNA expressions and membrane localization of all ARs were evaluated by qPCR and western blot. After the membrane localization of all ARs in astrocytes was being confirmed their individual adenosine binding ability was determined by radio-active ligand binding assay respectively. It was revealed that ARA1 had much superior adenosine binding ability than other AR subtypes. Functional study demonstrated that ARA1 potentially mediated an immune suppressive effect in astrocytes. The activation of ARA1 signaling lead to decreased IL-12 and IL-23 production, and decreased chemokine production, including CCL2, CXCL8 and IP-10. When interacted with CD4 cells ARA1 agonist pre-treated astrocytes showed hindered ability of stimulating CD4 cells to secret IL-17 and IFN-γ and inducing CD4 cells' chemo taxi. Finally, in vivo experiment confirmed that local administration of ARA1agonist ameliorated EAE in wild type B6 recipients, but not Ara1-/- recipients. As a conclusion, this paper suggested that adenosine receptor A1 subtype predominantly binds adenosine in astrocytes and mediates an immunosuppressive effect.
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Adenosina/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/inmunología , Receptor de Adenosina A1/metabolismo , Adenosina/farmacología , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , Técnicas de Cocultivo , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Inmunosupresores/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Purinérgicos/farmacología , ARN Mensajero/metabolismo , Receptor de Adenosina A1/genéticaRESUMEN
BACKGROUND: There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). OBJECTIVES: The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. METHOD: CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists. All samples were measured using a commercial enzyme-linked immunosorbent assay. Statistical analyses were performed using Prism software. RESULTS: Compared to the controls, the ALS patients displayed significantly increased levels of NF-L; these values were negatively correlated with the ALSFRS-r score and positively correlated with the decrease in ALSFRS-r score, DPR, and UMN score. There was no correlation between levels of NF-L and duration. In addition, the cumulative survival rate in ALS patients with a low level of NF-L was higher than in patients with a high level of NF-L. CONCLUSIONS: NF-L levels increased in CSF and serum of patients with ALS. NF-L may thus be a neurodegenerative biomarker for predicting ALS severity and progression, and the survival of patients with this disease.
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Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Biomarcadores , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Adulto , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Filamentos Intermedios/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
The dysfunction of spatial cognition is a character to various neurological disorders and therapeutic strategy. However, it is limited to known risk factors clinically so far. Gastrin releasing peptide (GRP) signaling is a neuropeptide system mediating emotional memory events. However, the effects of GRP agonist on spatial cognition and hippocampal synaptic plasticity are rarely investigated, especially in pathologic condition. This study was designed to investigate the long-term effects of GRPR agonist, bombesin, against cognitive impairment induced by chronic cerebral ischemia in rats and its possible mechanisms. Our results revealed that bombesin administration (30⯵g/kg/day, for 14 continuous days) significantly protected the cognitive and synaptic plasticity impairments as assessed by the Morris water maze and long-term potentiation tests. The mechanism studies demonstrated that bombesin significantly alleviated the decreased activity of total superoxide dismutase (T-SOD), catalase (CAT) and altered the increased the content of malondialdehyde (MDA). Besides, the decreased expression of synapse plasticity-related proteins, calcium- calmodulin- dependent protein kinase II (CaMKII) and synaptophysin (SYP) in the hippocampus were increased with drug treatment. In conclusion, bombesin could protect the oxidative stress and expression of proteins, which were important for synaptic plasticity and cognitive function impairment induced by chronic cerebral ischemia. Our study is presented to provide novel insights into the effects of bombesin on spatial learning and memory, which should be further explored as a potential drug in disorders involving deficits in cognitive function.
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Bombesina/uso terapéutico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Plasticidad Neuronal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Bombesina/farmacología , Isquemia Encefálica/patología , Catalasa/metabolismo , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Immunity and inflammation play critical roles in the pathogenesis of acute ischemic stroke. Therefore, immune intervention, as a new therapeutic strategy, is worthy of exploration. Here, we tested the inflammation modulator, vinpocetine, for its effect on the outcomes of stroke. For this multi-center study, we recruited 60 patients with anterior cerebral circulation occlusion and onset of stroke that had exceeded 4.5 h but lasted less than 48 h. These patients, after random division into two groups, received either standard management alone (controls) or standard management plus vinpocetine (30 mg per day intravenously for 14 consecutive days, Gedeon Richter Plc., Hungary). Vinpocetine treatment did not change the lymphocyte count; however, nuclear factor kappa-light-chain-enhancer of activated B cell activation was inhibited as seen not only by the increased transcription of IκBα mRNA but also by the impeded phosphorylation and degradation of IκBα and subsequent induction of pro-inflammatory mediators. These effects led to significantly reduced secondary lesion enlargement and an attenuated inflammation reaction. Compared to controls, patients treated with vinpocetine had a better recovery of neurological function and improved clinical outcomes during the acute phase and at 3-month follow-up. These findings identify vinpocetine as an inflammation modulator that could improve clinical outcomes after acute ischemic stroke. This study also indicated the important role of immunity and inflammation in the pathogenesis of acute ischemic stroke and the significance of immunomodulatory treatment. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov . Identifier: NCT02878772.
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Inflamación , FN-kappa B/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/complicaciones , Alcaloides de la Vinca/uso terapéutico , Adulto , Anciano , Isquemia Encefálica/complicaciones , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Estudios de Seguimiento , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , FN-kappa B/genética , ARN Mensajero/metabolismo , Estadísticas no Paramétricas , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
Introduction: To analyze the risk factors of carotid plaque (CP) and carotid common artery intima-media thickening (CCAIMT) and the association between the risk factors and CP numbers and the side of the CCAIMT in a high-stroke-risk population. Methods: Carotid ultrasonography was conducted in 2025 participants with high stroke risk. Participants were divided into different groups according to the results of the ultrasound. The risk factors and blood biochemical indices were recorded. Results: The presence of CP and CCAIMT were 38.9% and 24.8% respectively. Multivariate logistic regression indicated that the risk factors of CP were age, high LDL-C and FBG levels, male gender, stroke, diabetes, hypertension, and tobacco use. Compared with participants without CPs, the participants who were male, and older in age, with risk factors of tobacco use, diabetes, high LDL-C levels, and a family history of hypertension were likely to have a single CP, whereas the participants with risk factors of tobacco use, diabetes, hypertension, male gender, older age, high LDL-C levels, stroke and AF or valvulopathy were prone to have multiple CPs. The risk factors of CCAIMT were male gender, stroke, hypertension, diabetes, AF or valvulopathy, tobacco use and age. Compared with the N-CCAIMT subgroup, the risk factors of left CCAIMT were tobacco use, diabetes, male gender, and age. The risk factors of right CCAIMT were male gender, high FBG levels, age, AF or valvulopathy. The risk factors of dual CCAIMT were high frequency of drinking milk, tobacco use, male gender, age, stroke, and hypertension. Conclusion: These findings revealed the risk factors of CP and CCAIMT, and an association between the risk factors and the CP numbers and the side of the CCAIMT.
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Arteria Carótida Común/diagnóstico por imagen , Placa Aterosclerótica , Accidente Cerebrovascular , Túnica Íntima , Túnica Media , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Túnica Íntima/diagnóstico por imagen , Túnica Íntima/patología , Túnica Media/diagnóstico por imagen , Túnica Media/patología , Ultrasonografía/métodosRESUMEN
OBJECTIVES: The aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis. METHODS: Serum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS-r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model. RESULTS: A total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP-1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP-1 levels were associated with worse disease severity and faster progression, and the IFN-γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN-γ in the CSF had shorter overall survival. CONCLUSIONS: We demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.
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Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/fisiopatología , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To examine the neuroprotective effects of FGF-2 and explore the underlying mechanisms involved in its effects on neural precursor cells (NPCs) and S-IR boutons. METHODS: The mice models were established, and the animals were randomly divided into 3 groups: non-transgenic wild type group (WT), superoxide dismutase (SOD)1 G93A G1H transgenic group (SOD1), and fibroblast growth factor (FGF)-2-treated group (FGF-2), each group 40 mice. Mice of FGF-2 group were treated with FGF-2 at postnatal day 60 (P60). These three groups were examined at postnatal day 90 (P90) and 120 (P120). The changes of NPCs and S-IR boutons were checked by means of immunohistochemical detection. RESULTS: When mice were examined at P90 and P120, the number of Nestin(+) NPCs was (47±24) and (147±45) in the SOD1 group, (77±27) and (285±103) in the FGF-2 group. A marked increase was detected in the FGF-2 mice compared to the SOD1 mice at P120 (P<0.01). At P120 there was a clear decrease in the density of S-IR boutons in the SOD1 (0.5±0.1) and FGF-2 (0.8±0.1) mice compared to the WT (0.9±0.1) mice, but a more significant decrease in the density of S-IR boutons was detected in the SOD1 mice compared to the FGF-2 mice (P<0.05). CONCLUSION: FGF-2 may be a useful treatment to provide neuroprotection against neurodegeneration in amyotrophic lateral sclerosis (ALS) by encouraging the proliferation of NPCs and delaying the decrease in the density of S-IR boutons.
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Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Factor 2 de Crecimiento de Fibroblastos/farmacología , Células-Madre Neurales/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Superóxido Dismutasa/genéticaRESUMEN
OBJECTIVES: To explore whether the levels of IFN-γ in cerebral spinal fluid (CSF) and serum are elevated in ALS patients and to analyze the correlations between the IFN-γ levels and disease progression. METHODS: CSF and serum samples were obtained from 52 ALS patients and 31 non-ALS patients. The levels of IFN-γ in CSF and serum were assessed, and disease progression parameters, including the disease interval (months from onset, MFO), the revised ALS Functional Rating Scale (ALSFRS-r) score and the disease progression rate (DPR) were analyzed by registered neurologists. All samples were measured using a commercial enzyme-linked immunosorbent assay. Statistical analyses were performed using Prism software. RESULTS: Compared to the non-ALS patients, the ALS patients displayed significantly increased levels of IFN-γ in both CSF and serum, and these values consistently correlated with disease progression. CONCLUSIONS: These results demonstrated that IFN-γ in CSF may serve as a biomarker of ALS differentiation and progression. CSF IFN-γ was a more reliable biomarker of disease diagnosis and progression than serum IFN-γ.
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Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/patología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Humanos , Interferón gamma/sangre , Interferón gamma/líquido cefalorraquídeo , Masculino , Persona de Mediana EdadRESUMEN
In clinical settings, cerebral infarct is a common disease of older adults, which usually increases the risk of cognitive impairment. This study aims to assess the quantitative electroencephalography (qEEG) as a predictive biomarker for the development of cognitive impairment, post-cerebral infarcts, in subjects from the Department of Neurology. They underwent biennial EEG recording. Cerebral infarct subjects, with follow-up cognitive evaluation, were analyzed for qEEG measures of background rhythm frequency (BRF) and relative δ, θ, α, and ß band power. The relationship between cognitive impairment and qEEG, and other possible predictors, was assessed by Cox regression. The results showed that the risk hazard of developing cognitive impairment was 14 times higher for those with low BRF than for those with high BRF (P < .001). Hazard ratio (HR) was also significant for more than median θ band power (HR = 5, P = .002) compared with less than median θ band power. The HRs for δ, α, and ß bands were equal to the baseline demographic, and clinical characteristics were not significantly different. In conclusion, qEEG measures of BRF, and relative power in θ band, are potential predictive biomarkers for cognitive impairment in patients with cerebral infarcts. These biomarkers might be valuable in early prediction of cognitive impairment in patients with cerebral infarcts.
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Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Electroencefalografía/estadística & datos numéricos , Ritmo Teta , Anciano , Biomarcadores , Causalidad , Infarto Cerebral/fisiopatología , China/epidemiología , Trastornos del Conocimiento/fisiopatología , Diagnóstico por Computador/métodos , Femenino , Humanos , Incidencia , Masculino , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: To explore whether LIF could promote the proliferation of neural precursor cells (NPCs) and to analyze the correlation between increased NPCs and FluoroGold (FG) labeled neurons in mice after spinal cord injury (SCI). METHODS: Motor behavior was assessed using Rotarod and Platform Hang tests; neurons in the corticospinal and rubrospinal systems were labeled with FG, NPCs were immustained with nestin-FITC conjugate. The numbers of FG-labeled neurons and NPCs were estimated, and the correlation between FG-labeled neurons and NPCs was assessed. RESULTS: Mice in the SCI group showed negligible recovery of locomotor behavior; in contrast, mice in the LIF group showed a statically significant improvement. Both FG-labeled neurons and NPCs were significantly increased in the LIF group compared to the SCI group, and this increase in FG-labeled neurons and NPCs showed a clear association above the lesion level. CONCLUSIONS: LIF could promote locomotive behaviors in mice post-SCI by encouraging the proliferation of NPCs; LIF may in fact be a potential cytokine for the induction of NPCs post-SCI.
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Factor Inhibidor de Leucemia/uso terapéutico , Células-Madre Neurales/citología , Neuronas/citología , Traumatismos de la Médula Espinal/terapia , Animales , Proliferación Celular , Femenino , Factor Inhibidor de Leucemia/administración & dosificación , Locomoción , Masculino , Ratones , Ratones Endogámicos C57BL , Células-Madre Neurales/patología , Neurogénesis , Neuronas/patología , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder involving both upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Vascular endothelial growth factor (VEGF) was originally described as a factor with a regulatory role in vascular growth and development, and now it also functions as a neurotrophic factor protecting motoneurons from insults such as oxidative stress, hypoxia and glutamate-excitotoxicity, but the role of VEGF in ALS is still unclear. The aim of this study is to measure cerebrospinal fluid (CSF) and serum VEGF levels in patients with ALS, and to investigate whether there are correlations between CSF and serum VEGF levels and clinical parameters of the disease and whether VEGF has a prognostic and evaluating potential for ALS. Results showed that VEGF levels were found to increase significantly in CSF and serum in ALS patients studied; they were positively and significantly correlated with the disease duration in ALS patients and inversely and significantly correlated with disease progression rate (DPR) of ALS patients. Moreover, CSF and serum from ALS patients with long duration and slow disease progression rate revealed higher VEGF levels as compared to ALS patients with short duration and rapid disease progression rate. In conclusion, VEGF upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased duration and slow disease progression rate. We propose that VEGF may be a useful biomarker having the prognostic and evaluating potential for ALS.