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1.
RSC Med Chem ; 15(7): 2226-2253, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39026645

RESUMEN

With the development of society and the improvement of people's living standards, there is an increasing demand for melanin-inhibiting products that prioritize health, safety, and efficacy. Therefore, the development of natural products that can safely and efficiently inhibit melanin synthesis is of great social significance and has significant market potential. In this paper, by reviewing the literature reported in recent years, we summarized the natural products with inhibition of melanin synthesis effects that have been put into or not yet put into the market, and classified them according to the chemical groups of their compounds or the extraction methods of the natural products. Through the summary analysis, we found that these compounds mainly include terpenoids, phenylpropanoids, flavonoids and so on, while the natural product extracts mainly include methanol extracts, ethanol extracts, and aqueous extracts. Their main inhibition of melanin synthesis mechanisms include: (1) direct inhibition of tyrosinase activity; (2) down-regulation of the α-MSH-MC1R, Wnt, NO, PI3K/Akt and MAPK pathways through the expression of MITF and its downstream genes TYR, TRP-1, and TRP-2; (3) antioxidant; (4) inhibition of melanocyte growth through cytotoxicity; (5) inhibition of melanosome production and transport. This paper provides an in-depth discussion on the research progress of whitening natural products and their market value. The aim is to offer guidance for future research and development of natural skin whitening products.

2.
Environ Toxicol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041630

RESUMEN

Asparagus officinalis (ASP) has antioxidation, anti-inflammatory, antiaging, and immune system-enhancing effects. We explored the preventive and therapeutic consequences of ASP on the brain damage elicited by fluorosis through network pharmacology and in vivo experimental validation. We ascertained the pharmaceutically active ingredients and drug targets of ASP from the Traditional Chinese Medicine Systems Pharmacology database, predicted the disease targets of fluorosis-induced brain injury using GeneCards and Online Mendelian Inheritance in Man databases, obtained target protein-protein interaction networks in the Search Tool for the Retrieval of Interacting Genes/Proteins database, used Cytoscape to obtain key targets and active ingredients, and conducted enrichment analyses of key targets in the Database for Annotation, Visualization and Integrated Discovery. Enrichment analyses showed that "mitogen-activated protein kinase" (MAPK), "phosphoinositide 3-kinase/protein kinase B" (PI3K-Akt), "nuclear factor-kappa B" (NF-κB), and the "neurotrophin signaling pathway" were the most enriched biological processes and signaling pathways. ASP could alleviate fluorosis-based injury, improve brain-tissue damage, increase urinary fluoride content, and improve oxidation levels and inflammatory-factor levels in the body. ASP could also reduce dental fluorosis, bone damage, fluoride concentrations in blood and bone, and accumulation of lipid peroxide. Upon ASP treatment, expression of silent information regulator (SIRT)1, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), MAPK, NF-κB, PI3K, Akt, and B-cell lymphoma-2 in rat brain tissue increased gradually, whereas that of Bax, caspase-3, and p53 decreased gradually. We demonstrated that ASP could regulate the brain damage caused by fluorosis through the SIRT1/BDNF/TrkB signaling pathway, and reported the possible part played by ASP in preventing and treating fluorosis.

3.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(3): 612-619, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38932549

RESUMEN

Joint attention deficit is one of the core disorders in children with autism, which seriously affects the development of multiple basic skills such as language and communication. Virtual reality scene intervention has great potential in improving joint attention skills in children with autism due to its good interactivity and immersion. This article reviewed the application of virtual reality based social and nonsocial scenarios in training joint attention skills for children with autism in recent years, summarized the problems and challenges of this intervention method, and proposed a new joint paradigm for social scenario assessment and nonsocial scenario training. Finally, it looked forward to the future development and application prospects of virtual reality technology in joint attention skill training for children with autism.


Asunto(s)
Atención , Trastorno Autístico , Realidad Virtual , Humanos , Trastorno Autístico/terapia , Niño
4.
Org Lett ; 26(22): 4690-4694, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38804574

RESUMEN

Zn-mediated generation of alkoxyl radicals from N-alkoxyphthalimides emerged as an efficient approach for forming diverse and valuable alkyl radicals through ß-scission or a hydrogen atom transfer process. The alkyl radical species can be further trapped by α-trifluoromethyl alkenes to construct a series of gem-difluoroalkenes.

5.
J Colloid Interface Sci ; 669: 886-895, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38749227

RESUMEN

Zinc metal anodes in aqueous electrolytes commonly face challenges such as dendrite growth and undesirable side reactions, limiting their application in the field of aqueous zinc-ion batteries (AZIBs) for energy storage. Drawing inspiration from industrial practices involving molybdenum salt solutions for metal modification, a polyoxometalate solution was formulated as a passivation solution for zinc anodes (referred to as MO solution). The formed passivation layer, referred to as the MO layer, exhibited a uniform and protective nature with a thickness of approximately 10 µm. The experimental results demonstrated that this passivation layer effectively suppressed side reactions at the zinc anode interface, as evidenced by lower corrosion current density for MO-Zn anodes. Additionally, the newly plated Zn was uniformly deposited atop the MO layer, ensuring coating integrity and inhibiting dendrite growth. As a result, under more demanding conditions such as a larger current of 8 mA cm-2, the MO-Zn anode displayed an extended cycle life exceeding 420 h in a symmetric battery, with an overpotential as low as 98 mV. This performance significantly outperformed that of commercially available pure Zn foils (with a cycle life of 60 h and an overpotential of 192 mV). Notably, a self-made Na-doped V2O5 served as the cathode (referred to as NaVO), forming the MO-Zn//NaVO full battery. Even under high current test conditions of 2 A/g, the specific capacity of the MO-Zn//NaVO full battery remained substantial at 152.83 mAh/g after 1000 cycles. Furthermore, pouch batteries assembled with NaVO//MO-Zn successfully illuminated small bulbs. This study offers a viable optimization strategy for AZIB anodes and demonstrates the potential of using polyoxometalate solution for etching zinc anodes to inhibit dendrite growth and interfacial corrosion of zinc metal anodes.

6.
J Neural Eng ; 21(3)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38812288

RESUMEN

Objective. Magnetoencephalography (MEG) shares a comparable time resolution with electroencephalography. However, MEG excels in spatial resolution, enabling it to capture even the subtlest and weakest brain signals for brain-computer interfaces (BCIs). Leveraging MEG's capabilities, specifically with optically pumped magnetometers (OPM-MEG), proves to be a promising avenue for advancing MEG-BCIs, owing to its exceptional sensitivity and portability. This study harnesses the power of high-frequency steady-state visual evoked fields (SSVEFs) to build an MEG-BCI system that is flickering-imperceptible, user-friendly, and highly accurate.Approach.We have constructed a nine-command BCI that operates on high-frequency SSVEF (58-62 Hz with a 0.5 Hz interval) stimulation. We achieved this by placing the light source inside and outside the magnetic shielding room, ensuring compliance with non-magnetic and visual stimulus presentation requirements. Five participants took part in offline experiments, during which we collected six-channel multi-dimensional MEG signals along both the vertical (Z-axis) and tangential (Y-axis) components. Our approach leveraged the ensemble task-related component analysis algorithm for SSVEF identification and system performance evaluation.Main Results.The offline average accuracy of our proposed system reached an impressive 92.98% when considering multi-dimensional conjoint analysis using data from both theZandYaxes. Our method achieved a theoretical average information transfer rate (ITR) of 58.36 bits min-1with a data length of 0.7 s, and the highest individual ITR reached an impressive 63.75 bits min-1.Significance.This study marks the first exploration of high-frequency SSVEF-BCI based on OPM-MEG. These results underscore the potential and feasibility of MEG in detecting subtle brain signals, offering both theoretical insights and practical value in advancing the development and application of MEG in BCI systems.


Asunto(s)
Interfaces Cerebro-Computador , Potenciales Evocados Visuales , Magnetoencefalografía , Estimulación Luminosa , Humanos , Magnetoencefalografía/métodos , Potenciales Evocados Visuales/fisiología , Adulto , Masculino , Femenino , Estimulación Luminosa/métodos , Adulto Joven , Corteza Visual/fisiología
7.
Case Rep Infect Dis ; 2024: 7219952, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737750

RESUMEN

Over 200 different serogroups of Vibrio cholerae based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139. Non-O1/non-O139 V. cholerae serogroups generally do not produce the cholera-causing toxin but do sporadically cause gastroenteritis and extra-intestinal infections. Recently, however, bloodstream infections caused by non-O1/non-O139 V. cholerae are being increasingly reported, and these infections are associated with high mortality in immunocompromised hosts. We describe a case of non-O1/non-O139 V. cholerae bacteremia in a patient with autoimmune pancreatitis and stenosis of the intra- and extrahepatic bile ducts. The clinical manifestations of bacteremia were fever and mild digestive symptoms. The blood cultures showed V. cholerae, which was identified as a non-O1, non-O139 serogroup by slide agglutination tests and PCR. The bloodstream infection of the patient was likely caused by the consumption of contaminated seafood at a banquet. The patient recovered after the administration of a third-generation cephalosporin. Non-O1/non-O139 V. cholerae infection presents with or without gastrointestinal manifestations; close attention should be paid to the possibility of disseminated non-O1/non-O139 V. cholerae infection in high-risk patients.

8.
Brain ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739753

RESUMEN

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

9.
J Affect Disord ; 356: 105-114, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38580036

RESUMEN

BACKGROUND: Seeking objective quantitative indicators is important for accurately recognizing major depressive disorder (MDD). Lempel-Ziv complexity (LZC), employed to characterize neurological disorders, faces limitations in tracking dynamic changes in EEG signals due to defects in the coarse-graining process, hindering its precision for MDD objective quantitative indicators. METHODS: This work proposed Adaptive Permutation Lempel-Ziv Complexity (APLZC) and Adaptive Weighted Permutation Lempel-Ziv Complexity (AWPLZC) algorithms by refining the coarse-graining process and introducing weight factors to effectively improve the precision of LZC in characterizing EEGs and further distinguish MDD patients better. APLZC incorporated the ordinal pattern, while False Nearest Neighbor and Mutual Information algorithms were introduced to determine and adjust key parameters adaptively. Furthermore, we proposed AWPLZC by assigning different weights to each pattern based on APLZC. Thirty MDD patients and 30 healthy controls (HCs) were recruited and their 64-channel resting EEG signals were collected. The complexities of gamma oscillations were then separately computed using LZC, APLZC, and AWPLZC algorithms. Subsequently, a multi-channel adaptive K-nearest neighbor model was constructed for identifying MDD patients and HCs. RESULTS: LZC, APLZC, and AWPLZC algorithms achieved accuracy rates of 78.29 %, 90.32 %, and 95.13 %, respectively. Sensitivities reached 67.96 %, 85.04 %, and 98.86 %, while specificities were 88.62 %, 95.35 %, and 89.92 %, respectively. Notably, AWPLZC achieved the best performance in accuracy and sensitivity, with a specificity limitation. LIMITATION: The sample size is relatively small. CONCLUSION: APLZC and AWPLZC algorithms, particularly AWPLZC, demonstrate superior effectiveness in differentiating MDD patients from HCs compared with LZC. These findings hold significant clinical implications for MDD diagnosis.


Asunto(s)
Algoritmos , Trastorno Depresivo Mayor , Electroencefalografía , Humanos , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico , Adulto , Femenino , Masculino , Procesamiento de Señales Asistido por Computador , Persona de Mediana Edad , Estudios de Casos y Controles , Sensibilidad y Especificidad
10.
Curr Biol ; 34(9): 1866-1879.e6, 2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38608677

RESUMEN

Prefrontal (PFC) and hippocampal (HPC) sequences of neuronal firing modulated by theta rhythms could represent upcoming choices during spatial memory-guided decision-making. How the PFC-HPC network dynamically coordinates theta sequences to predict specific goal locations and how it is interrupted in memory impairments induced by amyloid beta (Aß) remain unclear. Here, we detected theta sequences of firing activities of PFC neurons and HPC place cells during goal-directed spatial memory tasks. We found that PFC ensembles exhibited predictive representation of the specific goal location since the starting phase of memory retrieval, earlier than the hippocampus. High predictive accuracy of PFC theta sequences existed during successful memory retrieval and positively correlated with memory performance. Coordinated PFC-HPC sequences showed PFC-dominant prediction of goal locations during successful memory retrieval. Furthermore, we found that theta sequences of both regions still existed under Aß accumulation, whereas their predictive representation of goal locations was weakened with disrupted spatial representation of HPC place cells and PFC neurons. These findings highlight the essential role of coordinated PFC-HPC sequences in successful memory retrieval of a precise goal location.


Asunto(s)
Objetivos , Hipocampo , Corteza Prefrontal , Memoria Espacial , Ritmo Teta , Corteza Prefrontal/fisiología , Ritmo Teta/fisiología , Animales , Hipocampo/fisiología , Masculino , Memoria Espacial/fisiología , Neuronas/fisiología , Ratones
11.
Int J Surg ; 110(6): 3166-3177, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38445521

RESUMEN

BACKGROUND: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, the authors propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS). METHODS: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or MRI scans within 24 h of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), the authors evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis. RESULTS: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3-5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and three control subjects developed incident CI. The CT interobserver reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBE-HCNNSS scale (OR 3.322, 95% CI: 2.312-7.237, P =0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort. CONCLUSION: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment.


Asunto(s)
Edema Encefálico , Disfunción Cognitiva , Hematoma , Hemorragia Subaracnoidea , Humanos , Masculino , Femenino , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Persona de Mediana Edad , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Estudios de Casos y Controles , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Hematoma/etiología , Anciano , Tomografía Computarizada por Rayos X , Adulto , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/diagnóstico por imagen , Imagen por Resonancia Magnética
12.
Artículo en Inglés | MEDLINE | ID: mdl-38517720

RESUMEN

Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) have emerged as a prominent technology due to their high information transfer rate, rapid calibration time, and robust signal-to-noise ratio. However, a critical challenge for practical applications is performance degradation caused by user fatigue during prolonged use. This work proposes novel methods to address this challenge by dynamically adjusting data acquisition length and updating detection models based on a fatigue-aware stopping strategy. Two 16-target SSVEP-BCIs were employed, one using low-frequency and the other using high-frequency stimulation. A self-recorded fatigue dataset from 24 subjects was utilized for extensive evaluation. A simulated online experiment demonstrated that the proposed methods outperform the conventional fixed stopping strategy in terms of classification accuracy, information transfer rate, and selection time, irrespective of stimulation frequency. These findings suggest that the proposed approach can significantly improve SSVEP-BCI performance under fatigue conditions, leading to superior performance during extended use.


Asunto(s)
Interfaces Cerebro-Computador , Humanos , Electroencefalografía/métodos , Potenciales Evocados Visuales , Estimulación Luminosa/métodos , Fatiga , Algoritmos
14.
Artículo en Inglés | MEDLINE | ID: mdl-38498742

RESUMEN

Depression is one of the most serious mental disorders affecting modern human life and is often caused by chronic stress. Dopamine system dysfunction is proposed to contribute to the pathophysiology of chronic stress, especially the ventral tegmental area (VTA) which mainly consists of dopaminergic neurons. Focused ultrasound stimulation (FUS) is a promising neuromodulation modality and multiple studies have demonstrated effective ultrasonic activation of cortical, subcortical, and related networks. However, the effects of FUS on the dopamine system and the potential link to chronic stress-induced depressive behaviors are relatively unknown. Here, we measured the effects of FUS targeting VTA on the improvement of depression-like behavior and evaluated the dopamine concentration in the downstream region - medial prefrontal cortex (mPFC). We found that targeting VTA FUS treatment alleviated chronic restraint stress (CRS) -induced anhedonia and despair behavior. Using an in vivo photometry approach, we analyzed the dopamine signal of mPFC and revealed a significant increase following the FUS, positively associated with the improvement of anhedonia behavior. FUS also protected the dopaminergic neurons in VTA from the damage caused by CRS exposure. Thus, these results demonstrated that targeting VTA FUS treatment significantly rescued the depressive-like behavior and declined dopamine level of mPFC induced by CRS. These beneficial effects of FUS might be due to protection in the DA neuron of VTA. Our findings suggest that FUS treatment could serve as a new therapeutic strategy for the treatment of stress-related disorders.


Asunto(s)
Anhedonia , Dopamina , Humanos , Corteza Prefrontal/fisiología , Área Tegmental Ventral/fisiología , Neuronas/fisiología , Neuronas Dopaminérgicas/fisiología
15.
Nat Commun ; 15(1): 898, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38320986

RESUMEN

Previous work identified nociceptive Schwann cells that can initiate pain. Consistent with the existence of inherently mechanosensitive sensory Schwann cells, we found that in mice, the mechanosensory function of almost all nociceptors, including those signaling fast pain, were dependent on sensory Schwann cells. In polymodal nociceptors, sensory Schwann cells signal mechanical, but not cold or heat pain. Terminal Schwann cells also surround mechanoreceptor nerve-endings within the Meissner's corpuscle and in hair follicle lanceolate endings that both signal vibrotactile touch. Within Meissner´s corpuscles, two molecularly and functionally distinct sensory Schwann cells positive for Sox10 and Sox2 differentially modulate rapidly adapting mechanoreceptor function. Using optogenetics we show that Meissner's corpuscle Schwann cells are necessary for the perception of low threshold vibrotactile stimuli. These results show that sensory Schwann cells within diverse glio-neural mechanosensory end-organs are sensors for mechanical pain as well as necessary for touch perception.


Asunto(s)
Percepción del Tacto , Tacto , Ratones , Animales , Tacto/fisiología , Nocicepción , Percepción del Tacto/fisiología , Mecanorreceptores/fisiología , Células de Schwann , Dolor , Umbral Sensorial
16.
J Integr Neurosci ; 23(2): 33, 2024 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-38419437

RESUMEN

BACKGROUND: Emotions are thought to be related to distinct patterns of neural oscillations, but the interactions among multi-frequency neural oscillations during different emotional states lack full exploration. Phase-amplitude coupling is a promising tool for understanding the complexity of the neurophysiological system, thereby playing a crucial role in revealing the physiological mechanisms underlying emotional electroencephalogram (EEG). However, the non-sinusoidal characteristics of EEG lead to the non-uniform distribution of phase angles, which could potentially affect the analysis of phase-amplitude coupling. Removing phase clustering bias (PCB) can uniform the distribution of phase angles, but the effect of this approach is unknown on emotional EEG phase-amplitude coupling. This study aims to explore the effect of PCB on cross-frequency phase-amplitude coupling for emotional EEG. METHODS: The technique of removing PCB was implemented on a publicly accessible emotional EEG dataset to calculate debiased phase-amplitude coupling. Statistical analysis and classification were conducted to compare the difference in emotional EEG phase-amplitude coupling prior to and post the removal of PCB. RESULTS: Emotional EEG phase-amplitude coupling values are overestimated due to PCB. Removing PCB enhances the difference in coupling strength between fear and happy emotions in the frontal lobe. Comparable emotion recognition performance was achieved with fewer features after removing PCB. CONCLUSIONS: These findings suggest that removing PCB enhances the difference in emotional EEG phase-amplitude coupling patterns and generates features that contain more emotional information. Removing PCB may be advantageous for analyzing emotional EEG phase-amplitude coupling and recognizing human emotions.


Asunto(s)
Electroencefalografía , Emociones , Humanos , Electroencefalografía/métodos , Emociones/fisiología , Miedo , Análisis por Conglomerados , Lóbulo Frontal
17.
Cogn Neurodyn ; 18(1): 173-184, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38406194

RESUMEN

It is emphasized in the Self-regulated learning (SRL) framework that self-monitoring of learning state is vital for students to keep effective in studying. However, it's still challenging to get an accurate and timely understanding of their learning states during classes. In this study, we propose to use electrodermal activity (EDA) signals which are deemed to be associated with physiological arousal state to predict the college student's classroom performance. Twenty college students were recruited to attend eight lectures in the classroom, during which their EDA signals were recorded simultaneously. For each lecture, the students should complete pre- and after-class tests, and a self-reported scale (SRS) on their learning experience. EDA indices were extracted from both time and frequency domains, and they were furtherly mapped to the student's learning efficiency. As a result, the indices relevant to the dynamic changes of EDA had significant positive correlations with the learning efficiency. Furthermore, compared with only using SRS, a combination with EDA indices had significantly higher accuracy in predicting the learning efficiency. In conclusion, our findings demonstrate that the EDA dynamics are sensitive to the changes in learning efficiency, suggesting a promising approach to predicting the classroom performance of college students.

18.
Phytomedicine ; 124: 155288, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38183698

RESUMEN

BACKGROUND: The scarcity of drugs targeting AML cells poses a significant challenge in AML management. Z-Ligustilide (Z-LIG), a phthalide compound, shows promising pharmacological potential as a candidate for AML therapy. However, its precise selective mechanism remains unclear. PURPOSE: In order to assess the selective inducement effects of Z-LIG on ferroptosis in AML cells and explore the possible involvement of the Nrf2/HO-1 pathway in the regulation of ferroptosis. METHODS: Through in vitro cell proliferation and in vivo tumor growth tests, the evaluation of Z-LIG's anticancer activity was conducted. Ferroptosis was determined by the measurement of ROS and lipid peroxide levels using flow cytometry, as well as the observation of mitochondrial morphology. To analyze the iron-related factors, western blot analysis was employed. The up-regulation of the Nrf2/HO-1 axis was confirmed through various experimental techniques, including CRISPR/Cas9 gene knockout, fluorescent probe staining, and flow cytometry. The efficacy of Z-LIG in inducing ferroptosis was further validated in a xenograft nude mouse model. RESULTS: Our study revealed that Z-LIG specifically triggered lipid peroxidation-driven cell death in AML cells. Z-LIG downregulated the total protein and nuclear entrance levels of IRP2, resulting in upregulation of FTH1 and downregulation of TFR1. Z-LIG significantly increased the susceptibility to ferroptosis by upregulating ACSL4 levels and simultaneously suppressing the activity of GPX4. Notably, the Nrf2/HO-1 pathway displayed a twofold impact in the ferroptosis induced by Z-LIG. Mild activation suppressed ferroptosis, while excessive activation promoted it, mainly driven by ROS-induced labile iron pool (LIP) accumulation in AML cells, which was not observed in normal human cells. Additionally, Nrf2 knockout and HO-1 knockdown reversed iron imbalance and mitochondrial damage induced by Z-LIG in HL-60 cells. Z-LIG effectively inhibited the growth of AML xenografts in mice, and Nrf2 knockout partially weakened its antitumor effect by inhibiting ferroptosis. CONCLUSION: Our study presents biological proof indicating that the selective initiation of ferroptosis in leukemia cells is credited to the excessive activation of the Nrf2/HO-1 pathway triggered by Z-LIG.


Asunto(s)
4-Butirolactona/análogos & derivados , Ferroptosis , Leucemia Mieloide Aguda , Humanos , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Leucemia Mieloide Aguda/metabolismo , Hierro/metabolismo
19.
Artículo en Inglés | MEDLINE | ID: mdl-38241112

RESUMEN

Deep brain stimulation (DBS) is an effective treatment for neurologic disease and its clinical effect is highly dependent on the DBS leads localization and current stimulating state. However, standard human brain imaging modalities could not provide direct feedback on DBS currents spatial distribution and dynamic changes. Acoustoelectric brain imaging (AEBI) is an emerging neuroimaging method that can directly map current density distribution. Here, we investigate in vivo AEBI of different DBS currents to explore the potential of DBS visualization using AEBI. According to the typical DBS stimulus parameters, four types of DBS currents, including time pattern, waveform, frequency, and amplitude are designed to implement AEBI experiments in living rat brains. Based on acoustoelectric (AE) signals, the AEBI images of each type DBS current are explored and the resolution is quantitatively analyzed for performance evaluation. Furtherly, the AE signals are decoded to characterize DBS currents from multiple perspectives, including time-frequency domain, spatial distribution, and amplitude comparation. The results show that in vivo transcranial AEBI can accurately locate the DBS contact position with a millimeter spatial resolution (< 2 mm) and millisecond temporal resolution (< 10 ms). Besides, the decoded AE signal at DBS contact position is capable of describing the corresponding DBS current characteristics and identifying current pattern changes. This study first validates that AEBI can localize in vivo DBS contact and characterize different DBS currents. AEBI is expected to develop into a noninvasive DBS real-time monitoring technology with high spatiotemporal resolution.


Asunto(s)
Estimulación Encefálica Profunda , Animales , Ratas , Humanos , Estimulación Encefálica Profunda/métodos , Encéfalo/fisiología , Cabeza , Neuroimagen
20.
J Integr Neurosci ; 23(1): 18, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38287841

RESUMEN

BACKGROUND: Affective computing has gained increasing attention in the area of the human-computer interface where electroencephalography (EEG)-based emotion recognition occupies an important position. Nevertheless, the diversity of emotions and the complexity of EEG signals result in unexplored relationships between emotion and multichannel EEG signal frequency, as well as spatial and temporal information. METHODS: Audio-video stimulus materials were used that elicited four types of emotions (sad, fearful, happy, neutral) in 32 male and female subjects (age 21-42 years) while collecting EEG signals. We developed a multidimensional analysis framework using a fusion of phase-locking value (PLV), microstates, and power spectral densities (PSDs) of EEG features to improve emotion recognition. RESULTS: An increasing trend of PSDs was observed as emotional valence increased, and connections in the prefrontal, temporal, and occipital lobes in high-frequency bands showed more differentiation between emotions. Transition probability between microstates was likely related to emotional valence. The average cross-subject classification accuracy of features fused by Discriminant Correlation Analysis achieved 64.69%, higher than that of single mode and direct-concatenated features, with an increase of more than 7%. CONCLUSIONS: Different types of EEG features have complementary properties in emotion recognition, and combining EEG data from three types of features in a correlated way, improves the performance of emotion classification.


Asunto(s)
Emociones , Miedo , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Reconocimiento en Psicología , Electroencefalografía/métodos , Análisis Discriminante
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