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Different movement paradigms have varying effects on stroke rehabilitation, and their mechanisms of action on the brain are not fully understood. This study aims to investigate disparities in brain network and functional connectivity of three movement paradigms (active, motor imagery, passive) on stroke recovery. EEG signals were recorded from 11 S patients (SP) and 13 healthy controls (HC) during fist clenching and opening tasks under the three paradigms. Brain networks were constructed to analyze alterations in brain network connectivity, node strength (NS), clustering coefficients (CC), characteristic path length (CPL), and small-world index(S). Our findings revealed increased activity in the contralateral motor area in SP and higher activity in the ipsilateral motor area in HC. In the beta band, SP exhibited significantly higher CC in motor imagery (MI) than in active and passive tasks. Furthermore, the small world index of SP during MI tasks in the beta band was significantly smaller than in the active and passive tasks. NS in the gamma band for SP during the MI paradigm was significantly higher than in the active and passive paradigms. These findings suggest reorganization within both ipsilateral and contralateral motor areas of stroke patients during MI tasks, providing evidence for neural restructuring. Collectively, these findings contribute to a deeper understanding of task-state brain network changes and the rehabilitative mechanism of MI on motor function.
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The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.
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Proliferação de Células , Camundongos Knockout , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Masculino , Camundongos , Ratos , Linhagem Celular , Coração/crescimento & desenvolvimento , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , MicropeptídeosRESUMO
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD.
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Doença de Alzheimer , Biomarcadores , Perfilação da Expressão Gênica , Rabfilina-3A , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Camundongos , Humanos , Biomarcadores/metabolismo , Rabfilina-3A/metabolismo , Rabfilina-3A/genética , Sinapses/metabolismo , Transcriptoma , Modelos Animais de Doenças , Camundongos Transgênicos , Neurônios/metabolismo , Análise de Célula Única/métodosRESUMO
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two common diseases that affect the elderly population worldwide. The identification of common genes associated with AD and T2DM holds promise for potential biomarkers and intriguing pathogenesis of these two complicated diseases. This study utilized a comprehensive approach by integrating transcriptome data from multiple cohorts, encompassing both AD and T2DM. The analysis incorporated various data types, including blood and tissue samples as well as single-cell datasets, allowing for a detailed assessment of gene expression patterns. From the brain region-specific single-cell analysis, PIP4K2A, which encodes phosphatidylinositol-5-phosphate 4-kinase type 2 alpha, was found to be expressed mainly in oligodendrocytes compared to other cell types. Elevated levels of PIP4K2A in AD and T2DM patients' blood were found to be associated with key cellular processes such as vesicle-mediated transport, negative regulation of autophagosome assembly, and cytosolic transport. The identification of PIP4K2A's potential roles in the cellular processes of AD and T2DM offers valuable insights into the development of biomarkers for diagnosis and therapy, especially in the complication of these two diseases.
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Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Oligodendroglia , Fosfotransferases (Aceptor do Grupo Álcool) , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Biomarcadores , Transcriptoma , Análise de Célula Única , Perfilação da Expressão Gênica , MultiômicaRESUMO
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and behavioral decline. Acrolein, an environmental pollutant and endogenous compound, is implicated in AD development. This research employs bibliometric analysis to assess current trends and key areas concerning acrolein-AD interaction. Methods: The Web of Science was used to extensively review literature on acrolein and AD. Relevant data were systematically gathered and analyzed using VOSviewer, CiteSpace, and an online bibliometric tool. Results: We identified 120 English publications in this specialized field across 19 journals. The Journal of Alzheimer's Disease was the most prominent. The primary contributors, both in terms of scientific output and influence, were the USA, the University of Kentucky, and Ramassamy C, representing countries/regions, institutions, and authors, respectively. In this field, the primary focus was on thoroughly studying acrolein, its roles, and its mechanisms in AD utilizing both in vivo and in vitro approaches. A significant portion of the research was based on proteomics, revealing complex molecular processes. The main focuses in the field were "oxidative stress," "lipid peroxidation," "amyloid-beta," and "cognitive impairment." Anticipated future research trajectories focus on the involvement of the internalization pathway, covering key areas such as synaptic dysfunction, metabolism, mechanisms, associations, neuroinflammation, inhibitors, tau phosphorylation, acrolein toxicity, brain infarction, antioxidants, chemistry, drug delivery, and dementia. Our analysis also supported our previous hypothesis that acrolein can interact with amyloid-beta to form a protein adduct leading to AD-like pathology and altering natural immune responses. Conclusion: This study provides a broad and all-encompassing view of the topic, offering valuable insights and guidance to fellow researchers. These emerging directions underscore the continuous exploration of the complexities associated with AD. The analyses and findings aim to enhance our understanding of the intricate relationship between acrolein and AD for future research.
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BACKGROUND: Electroacupuncture (EA) is a promising rehabilitation treatment for upper-limb motor recovery in stroke patients. However, the neurophysiological mechanisms underlying its clinical efficacy remain unclear. This study aimed to explore the immediate modulatory effects of EA on brain network functional connectivity and topological properties. METHODS: The randomized, single-blinded, self-controlled two-period crossover trial was conducted among 52 patients with subacute subcortical stroke. These patients were randomly allocated to receive either EA as the initial intervention or sham electroacupuncture (SEA) as the initial intervention. After a washout period of 24 hours, participants underwent the alternate intervention (SEA or EA). Resting state electroencephalography signals were recorded synchronously throughout both phases of the intervention. The functional connectivity (FC) of the parietofrontal network and small-world (SW) property indices of the whole-brain network were compared across the entire course of the two interventions. RESULTS: The results demonstrated that EA significantly altered ipsilesional parietofrontal network connectivity in the alpha and beta bands (alpha: Fâ =â 5.05, Pâ =â .011; beta: Fâ =â 3.295, Pâ =â .047), whereas no significant changes were observed in the SEA group. When comparing between groups, EA significantly downregulated ipsilesional parietofrontal network connectivity in both the alpha and beta bands during stimulation (alpha: tâ =â -1.998, Pâ =â .049; beta: tâ =â -2.342, Pâ =â .022). Significant differences were also observed in the main effects of time and the groupâ ×â time interaction for the SW index (time: Fâ =â 5.516, Pâ =â .026; groupâ ×â time: Fâ =â 6.892, Pâ =â .01). In terms of between-group comparisons, the EA group exhibited a significantly higher SW index than the SEA group at the post-stimulation stage (tâ =â 2.379, Pâ =â .018). CONCLUSION: These findings suggest that EA downregulates ipsilesional parietofrontal network connectivity and enhances SW properties, providing a potential neurophysiological mechanism for facilitating motor performance in stroke patients.
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Eletroacupuntura , Acidente Vascular Cerebral , Humanos , Eletroacupuntura/métodos , Estudos Cross-Over , Acidente Vascular Cerebral/terapia , Encéfalo , EletroencefalografiaRESUMO
BACKGROUND: Dual transcranial direct current stimulation (tDCS) over the bilateral primary somatosensory cortex (PSC) has potential benefits in stroke. In addition, compared with traditional rehabilitation training, sensorimotor training can significantly improve the sensorimotor function of patients. However, the efficacy of dual-tDCS combined with sensorimotor training in patients with subacute stroke is unknown. OBJECTIVE: To assess whether dual-tDCS may enhance the efficacy of sensorimotor training on the upper limb functions in patients with subacute stroke. In addition, this study aims to explore the potential clinical mechanism of this combination therapy. METHODS: We randomized 52 individuals with first-ever, unilateral subcortical stroke into the experimental group (n = 26) and the control group (n = 26). Patients in the experimental group received 20 min of dual-tDCS over the PSC and 40 min of sensorimotor training each session, while patients in the control group received sham dual-tDCS. The treatment cycle was a 1-h session of therapy each day, 5 days per week for 4 weeks. The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) subscale, Action Research Arm Test (ARAT), Box and Block test (BBT), Erasmus MC revised Nottingham sensory assessment scale (Em-NSA), Neurometer sensory nerve quantitative detector (CPT), the Barthel index (BI), and Hospital Anxiety and Depression Scale (HADS) were used to assess upper limb function, activities of daily living (ADL), and mental health before and after the 4-week treatment period. In addition, functional near-infrared spectroscopy (fNIRS) was used to explore potential clinical brain mechanisms. RESULTS: Both groups showed significant improvement in all clinical scales (All p < 0.05) after treatment. Compared with sham-tDCS plus sensorimotor training, active dual-tDCS coupled with sensorimotor training can significantly improve the FMA-UE, ARAT, Em-NSA-Stereognosis, and CPT-2K Hz. In addition, dual-tDCS combined with sensorimotor training can significantly activate the left pre-Motor and supplementary motor cortex (PM-SMC) and enhance the functional connection between the left somatosensory association cortex (SAC) and RPM-SMC. Furthermore, the difference of FMA-UE in the experimental group was positively correlated with the functional connectivity of RPM-SMC-LSAC (r = 0.815, p < 0.001). CONCLUSION: Dual-tDCS over the PSC combined with sensorimotor training can improve upper limb sensory and motor dysfunction, enhance ADL, and alleviate depression and anxiety for subacute stroke patients. Our results indicated that RPM-SMC-LSAC may be potential therapeutic targets for dual-tDCS in upper limb rehabilitation on stroke.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Atividades Cotidianas , Reabilitação do Acidente Vascular Cerebral/métodos , Recuperação de Função Fisiológica/fisiologia , Extremidade Superior , Resultado do TratamentoRESUMO
Primary health care (PHC) is the most effective way to improve people's health and well-being, and primary care services should act as the cornerstone of a resilient health system and the foundation of universal health coverage. To promote high quality development of PHC, an International Symposium on Quality Primary Health Care Development was held on December 4-5, 2023 in Beijing, China, and the participants have proposed and advocated the Beijing Initiative on Quality Primary Health Care Development. The Beijing Initiative calls on all countries to carry out and strengthen 11 actions: fulfill political commitment and accountability; achieve "health in all policies" through multisectoral coordination; establish sustainable financing; empower communities and individuals; provide community-based integrated care; promote the connection and integration of health services and social services through good governance; enhance training, allocation and motivation of health workforce, and medical education; expand application of traditional and alternative medicine for disease prevention and illness healing; empower PHC with digital technology; ensure access to medicinal products and appropriate technologies; and last, strengthen global partnership and international health cooperation. The Initiative will enrich the content of quality development of PHC, build consensus, and put forward policies for quality development of PHC in China in the new era, which are expected to make contributions in accelerating global actions.
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Atenção Primária à Saúde , Cobertura Universal do Seguro de Saúde , Humanos , Pequim , Atenção à Saúde , Qualidade da Assistência à SaúdeRESUMO
Background: The activation patterns and functional network characteristics between stroke survivors and healthy individuals based on resting-or task-state neuroimaging and neurophysiological techniques have been extensively explored. However, the discrepancy between stroke patients at different recovery stages remains unclear. Objective: To investigate the changes in brain connectivity and network topology between subacute and chronic patients, and hope to provide a basis for rehabilitation strategies at different stages after stroke. Methods: Fifteen stroke survivors were assigned to the subacute group (SG, N = 9) and chronic group (CG, N = 6). They were asked to perform hand grasping under active, passive, and MI conditions when recording EEG. The Fugl-Meyer Assessment Upper Extremity subscale (FMA_UE), modified Ashworth Scale (MAS), Manual Muscle Test (MMT), grip and pinch strength, modified Barthel Index (MBI), and Berg Balance Scale (BBS) were measured. Results: Functional connectivity analyses showed significant interactions on frontal, parietal and occipital lobes connections in each frequency band, particularly in the delta band. The coupling strength of premotor cortex, M1, S1 and several connections linked to frontal, parietal, and occipital lobes in subacute subjects were lower than in chronic subjects in low alpha, high alpha, low beta, and high beta bands. Nodal clustering coefficient (CC) analyses revealed that the CC in chronic subjects was higher than in subacute subjects in the ipsilesional S1 and occipital area, contralesional dorsolateral prefrontal cortex and parietal area. Characteristic path length (CPL) analyses showed that CPL in subacute subjects was lower than in chronic subjects in low beta, high beta, and gamma bands. There were no significant differences between subacute and chronic subjects for small-world property. Conclusion: Subacute stroke survivors were characterized by higher transfer efficiency of the entire brain network and weak local nodal effects. Transfer efficiency was reduced, the local nodal role was strengthened, and more neural resources needed to be mobilized to perform motor tasks for chronic survivors. Overall, these results may help to understand the remodeling pattern of the brain network for different post-stroke stages on task conditions and the mechanism of spontaneous recovery.
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Background: Brain-computer interfaces (BCIs) have been proven to be effective for hand motor recovery after stroke. Facing kinds of dysfunction of the paretic hand, the motor task of BCIs for hand rehabilitation is relatively single, and the operation of many BCI devices is complex for clinical use. Therefore, we proposed a functional-oriented, portable BCI equipment and explored the efficiency of hand motor recovery after a stroke. Materials and methods: Stroke patients were randomly assigned to the BCI group and the control group. The BCI group received BCI-based grasp/open motor training, while the control group received task-oriented guidance training. Both groups received 20 sessions of motor training in 4 weeks, and each session lasted for 30 min. The Fugl-Meyer assessment of the upper limb (FMA-UE) was applied for the assessment of rehabilitation outcomes, and the EEG signals were obtained for processing. Results: The progress of FMA-UE between the BCI group [10.50 (5.75, 16.50)] and the control group [5.00 (4.00, 8.00)] was significantly different (Z = -2.834, P = 0.005). Meanwhile, the FMA-UE of both groups improved significantly (P < 0.001). A total of 24 patients in the BCI group achieved the minimal clinically important difference (MCID) of FMA-UE with an effective rate of 80%, and 16 in the control group achieved the MCID, with an effective rate of 51.6%. The lateral index of the open task in the BCI group was significantly decreased (Z = -2.704, P = 0.007). The average BCI accuracy for 24 stroke patients in 20 sessions was 70.7%, which was improved by 5.0% in the final session compared with the first session. Conclusion: Targeted hand movement and two motor task modes, namely grasp and open, to be applied in a BCI design may be suitable in stroke patients with hand dysfunction. The functional-oriented, portable BCI training can promote hand recovery after a stroke, and it is expected to be widely used in clinical practice. The lateral index change of inter-hemispheric balance may be the mechanism of motor recovery. Trial registration number: ChiCTR2100044492.
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BACKGROUND: Sjogren's syndrome (SS) is a systemic autoimmune disease featured with a dry mouth and dry eyes. Several autoantibodies, including anti-SSA, anti-SSB, antinuclear antibodies can be detected in patients with SS. Oxidation-specific epitopes (OSEs) can be formed from malondialdehyde (MDA)-modified protein adducts and trigger chronic inflammation. In this study, our purposes were used serum levels of anti-MDA-modified peptide adducts autoantibodies to evaluate predictive performance by machine learning algorithms in primary Sjögren's syndrome (pSS) and assess the association between pSS and healthy controls. METHODS: Three novel MDA-modified peptide adducts, including immunoglobulin (Ig) gamma heavy chain 1 (IGHG1)102-131, complement factor H (CFAH)1045-1062, and Ig heavy constant alpha 1 (IGHA1)307-327 were identified and validated. Serum levels of protein, MDA-modified protein adducts, MDA, and autoantibodies recognizing unmodified peptides and MDA-modified peptide adducts were measured. Statistically significance in correlations and odds ratios (ORs) were estimated. RESULTS: The random forest classifier utilized autoantibodies combination composed of IgM anti-IGHG1102-131, IgM anti-IGHG1102-131 MDA and IgM anti-IGHA1307-327 achieved predictive performance as an accuracy of 88.0%, a sensitivity of 93.7%, and a specificity of 84.4% which may be as potential diagnostic biomarkers to differentiate patients with pSS from rheumatoid arthritis (RA), and secondary SS in RA and HCs. CONCLUSIONS: Our findings imply that low levels of IgA anti-IGHG1102-131 MDA (OR = 2.646), IgA anti-IGHG1102-131 (OR = 2.408), IgA anti-CFAH1045-1062 (OR = 2.571), and IgA anti-IGHA1307-327 (OR = 2.905) may denote developing risks of pSS, respectively.
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Artrite Reumatoide , Síndrome de Sjogren , Anticorpos Antinucleares , Autoanticorpos , Biomarcadores , Fator H do Complemento , Epitopos , Feminino , Humanos , Imunoglobulina A , Imunoglobulina M , Malondialdeído , Peptídeos , Síndrome de Sjogren/diagnósticoRESUMO
Goal. Stroke patients are usually accompanied by motor dysfunction, which greatly affects daily life. Electroacupuncture is a kind of nondrug therapy that can effectively improve motor function. However, the effect of electroacupuncture is hard to be measured immediately in clinic. This paper is aimed to reveal the instant changes in brain activity of three groups of stroke patients before, during, and after the electroacupuncture treatment by the EEG analysis in the alpha band and beta band. Methods. Seven different functional connectivity indicators including Pearson correlation coefficient, spectral coherence, mutual information, phase locking value, phase lag index, partial directed coherence, and directed transfer function were used to build the BCI-based brain network in stroke patients. Results and Conclusion. The results showed that the brain activity based on the alpha band of EEG decreased after the electroacupuncture treatment, while in the beta band of EEG, the brain activity decreased only in the first two groups. Significance. This method could be used to evaluate the effect of electroacupuncture instantly and quantitatively. The study will hopefully provide some neurophysiological evidence of the relationship between changes in brain activity and the effects of electroacupuncture. The study of BCI-based brain network changes in the alpha and beta bands before, during, and after electroacupuncture in stroke patients of different periods is helpful in adjusting and selecting the electroacupuncture regimens for different patients. The trial was registered on the Chinese clinical trial registry (ChiCTR2000036959).
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Interfaces Cérebro-Computador , Eletroacupuntura , Acidente Vascular Cerebral , Encéfalo , Eletroencefalografia/métodos , Humanos , Acidente Vascular Cerebral/terapiaRESUMO
Proprioceptive deficit is one of the common sensory impairments following stroke and has a negative impact on motor performance. However, evidence-based training procedures and cost-efficient training setups for patients with poststroke are still limited. We compared the effects of proprioceptive training versus nonspecific sensory stimulation on upper limb proprioception and motor function rehabilitation. In this multicenter, single-blind, randomized controlled trial, 40 participants with poststroke hemiparesis were enrolled from 3 hospitals in China. Participants were assigned randomly to receive proprioceptive training involving passive and active movements with visual feedback (proprioceptive training group [PG]; n = 20) or nonspecific sensory stimulation (control group [CG]; n = 20) 20 times in four weeks. Each session lasted 30 minutes. A clinical assessor blinded to group assignment evaluated patients before and after the intervention. The primary outcome was the change in the motor subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-M). Secondary outcomes were changes in box and block test (BBT), thumb localization test (TLT), the sensory subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-S), and Barthel Index (BI). The results showed that the mean change scores of FMA-UE were significantly greater in the PG than in the CG (p = 0.010 for FMA-UE-M, p = 0.033 for FMA-UE-S). The PG group was improved significantly in TLT (p = 0.010) and BBT (p = 0.027), while there was no significant improvement in TLT (p = 0.083) and BBT (p = 0.107) for the CG group. The results showed that proprioceptive training was effective in improving proprioception and motor function of the upper extremity in patients with poststroke. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000037808).
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Retroalimentação Sensorial/fisiologia , Paresia/reabilitação , Propriocepção/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/etiologia , Paresia/fisiopatologia , Projetos Piloto , Recuperação de Função Fisiológica/fisiologia , Método Simples-Cego , Acidente Vascular Cerebral/complicações , Resultado do TratamentoRESUMO
We and others have shown that MPM (micropeptide in mitochondria) regulates myogenic differentiation and muscle development. However, the roles of MPM in cancer development remain unknown. Here we revealed that MPM was downregulated significantly in human hepatocellular carcinoma (HCC) tissues and its decrease was associated with increased metastasis potential and HCC recurrence. Gain- and loss-of-function investigations disclosed that in vitro migration/invasion and in vivo liver/lung metastasis of hepatoma cells were repressed by restoring MPM expression and increased by silencing MPM. Mechanism investigations revealed that MPM interacted with NDUFA7. Mitochondrial complex I activity was inhibited by overexpressing MPM and enhanced by siMPM, and this effect of siMPM was attenuated by knocking down NDUFA7. The NAD+/NADH ratio, which was regulated by complex I, was reduced by MPM but increased by siMPM. Treatment with the NAD+ precursor nicotinamide abrogated the inhibitory effect of MPM on hepatoma cell migration. Further investigations showed that miR-17-5p bound to MPM and inhibited MPM expression. miR-17-5p upregulation was associated with MPM downregulation in HCC tissues. These findings indicate that a decrease in MPM expression may promote hepatoma metastasis by increasing mitochondrial complex I activity and the NAD+/NADH ratio.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Metástase NeoplásicaRESUMO
Objective: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, leading to disability and decreased quality of life. In past research and clinical studies, the lower limb function of DPN patients was often the principal subject of research, with little attention given to the upper limb and hand. Our goal was to assess and compare hand function between elderly diabetic patients with DPN and without DPN. Methods: A total of 52 diabetic patients were registered and underwent hand function assessments and electrodiagnostic tests. Dynamometer, pinch meter, Semmes Weinstein monofilaments, and the Purdue Pegboard Test (PPT) were used to assess the patients' grip strength, pinch strength, tactile sensory threshold, and hand dexterity. Results: Compared with the non-DPN group, the elderly DPN group showed worse thumb-middle fingertip pinch strength and thumb-little fingertip pinch strength in the dominant hand (3.50 (2.50, 4.25) vs. 4.50 (3.00, 5.00), p = 0.019; 1.50 (1.00, 2.00) vs. 2.50 (2.00, 3.00), p < 0.001); the elderly DPN group displayed worse thumb-middle fingertip pinch strength, thumb-ring fingertip pinch strength, and thumb-little fingertip pinch strength in the nondominant hand (3.50 (2.00, 4.50) vs. 4.00 (3.00, 5.00), p = 0.013; 2.50 (1.25, 3.00) vs. 3.00 (2.50, 3.50), p = 0.033; 1.00 (0.75, 2.25) vs. 2.50 (2.00, 2.50), p < 0.001). The elderly DPN group scored lower than the non-DPN group on the PPT test of assembly (13.96 ± 5.18 vs. 16.96 ± 4.61, t = 2.212, p = 0.032). Conclusion: Motor function limitation is the principal hand dysfunction in elderly patients with DPN, which is mainly manifested as a decline in fingertip pinch strength and a decrease in hand dexterity. This trial is registered with Clinical Trial Registry no. ChiCTR1900025358.
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Neuropatias Diabéticas/fisiopatologia , Mãos/fisiopatologia , Força Muscular/fisiologia , Força de Pinça/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Dinamômetro de Força Muscular , Condução Nervosa/fisiologiaRESUMO
Passive movement is an important mean of rehabilitation for stroke survivors in the early stage or with greater paralysis. The upper extremity robot is required to assist therapists with passive movement during clinical rehabilitation, while customizing is one of the crucial issues for robot-assisted upper extremity training, which fits the patient-centeredness. Robot-assisted teaching training could address the need well. However, the existing control strategies of teaching training are usually commanded by position merely, having trouble to achieve the efficacy of treatment by therapists. And deficiency of flexibility and compliance comes to the training trajectory. This research presents a novel motion control strategy for customized robot-assisted passive neurorehabilitation. The teaching training mechanism is developed to coordinate the movement of the shoulder and elbow, ensuring the training trajectory correspondence with human kinematics. Furthermore, the motion trajectory is adjusted by arm strength to realize dexterity and flexibility. Meanwhile, the torque sensor employed in the human-robot interactive system identifies movement intention of human. The goal-directed games and feedbacks promote the motor positivity of stroke survivors. In addition, functional experiments and clinical experiments are investigated with a healthy adult and five recruited stroke survivors, respectively. The experimental results present that the suggested control strategy not only serves with safety training but also presents rehabilitation efficacy.
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Terapia por Exercício , Reabilitação Neurológica/métodos , Robótica/métodos , Adulto , Idoso , Algoritmos , Braço/fisiopatologia , Fenômenos Biomecânicos , Desenho de Equipamento , Feminino , Fricção , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Modalidades de Fisioterapia , Amplitude de Movimento Articular , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Torque , Extremidade Superior/fisiopatologiaRESUMO
AIMS/INTRODUCTION: Carpal tunnel syndrome (CTS) and diabetic polyneuropathy (DPN) can occur together, and this concomitance is thought to be higher in diabetes patients. We aimed to examine and compare hand function in type 2 diabetes mellitus patients without CTS and DPN (CTS-DPN-), patients with CTS without DPN (CTS+DPN-), patients with DPN without CTS (CTS-DPN+), and patients with CTS and DPN (CTS+DPN+). MATERIALS AND METHODS: A total of 161 type 2 diabetes mellitus patients underwent physical examination and electrodiagnostic tests. Grip and pinch strengths, tactile sensory thresholds were measured for each participant. Purdue pegboard test was used in evaluating the hand dexterity of the participants. RESULTS: Of the 161 type 2 diabetes mellitus participants, 36 (22.4%) had both CTS and DPN. CTS participants had lower grip (26.6 ± 10.6 vs 35.2 ± 14.3, P < 0.001) and pinch (6.3 ± 2.6 vs 7.5 ± 2.9, P = 0.026) strengths compared with non-CTS participants, whereas DPN participants had elevated tactile sensory thresholds of both the second (2.8 [2.8-3.6] vs 2.4 [2.4-2.8], P < 0.001) and the fifth (2.8 [2.8-3.6] vs 2.4 [2.4-2.8], P < 0.001) fingers compared with non-DPN participants. The CTS+DPN+ group had lower Purdue pegboard test scores than other groups. Grip (r = 0.482, 0.530, 0.467, 0.498, all P < 0.001) and pinch (r = 0.246, P = 0.003; r = 0.265, P = 0.001; r = 0.264, P = 0.001; r = 0.235, P = 0.005) strengths were positively correlated with Purdue pegboard test scores, whereas tactile sensory thresholds were negatively correlated with Purdue pegboard test scores (r = -0.447 to -0.359, all P < 0.001). CONCLUSION: Type 2 diabetes mellitus patients with both DPN and CTS had lower grip and pinch strengths and decreased tactile sensation, both of which were correlated with poorer hand dexterity.
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Síndrome do Túnel Carpal/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Força da Mão , Tato , Idoso , Síndrome do Túnel Carpal/etiologia , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Feminino , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Flaccid paralysis in the upper extremity is a severe motor impairment after stroke, which exists for weeks, months, or even years. Electroacupuncture treatment is one of the most widely used TCM therapeutic interventions for poststroke flaccid paralysis. However, the response to electroacupuncture in different durations of flaccid stage poststroke as well as in the topological configuration of the cortical network remains unclear. The objectives of this study are to explore the disruption of the cortical network in patients in different durations of flaccid stage and observe dynamic network reorganization during and after electroacupuncture. Resting-state networks were constructed from 18 subjects with flaccid upper extremity by partial directed coherence (PDC) analysis of multichannel EEG. They were allocated to three groups according to time after flaccid paralysis: the short-duration group (those with flaccidity for less than two months), the medium-duration group (those with flaccidity between two months and six months), and the long-duration group (those with flaccidity over six months). Compared with short-duration flaccid subjects, weakened effective connectivity was presented in medium-duration and long-duration groups before electroacupuncture. The long-duration group has no response in the cortical network during electroacupuncture. The global network measures of EEG data (sPDC, mPDC, and N) indicated that there was no significant difference among the three groups. These results suggested that the network connectivity reduced and weakly responded to electroacupuncture in patients with flaccid paralysis for over six months. These findings may help us to modulate the formulation of electroacupuncture treatment according to different durations of the flaccid upper extremity.
Assuntos
Eletroacupuntura/métodos , Eletroencefalografia/métodos , Paralisia/fisiopatologia , Paralisia/terapia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Ritmo beta/fisiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paralisia/etiologia , Projetos Piloto , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients. METHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated. RESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA. CONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.
Assuntos
Artrite Reumatoide , Autoanticorpos , Aldeídos , Artrite Reumatoide/diagnóstico , Feminino , Humanos , Peptídeos , Espectrometria de Massas em TandemRESUMO
AIM: This study aimed to explore the association between socioeconomic status and urinary incontinence (UI). METHODS: We used data from the three waves of the Taiwan Longitudinal Study on Aging. This study included 2458 women and 2866 men aged ≥50 years. We used logistic random effects models to examine the associations of interest, adjusting for demographics, health-related behaviors, disability, number of health conditions and prostate problems for men and numbers of children for women. RESULTS: In adjusted analysis, women with secondary education least frequently reported UI compared with women with no formal education (adjusted odds ratio [AOR] 0.41, 95% confidence interval [95% CI] 0.22-0.79). Those with severe economic hardships (vs those with no economic hardships) had an increased risk of UI among men and women (AOR 2.71, 95% CI 1.72-4.25 and AOR 1.94, 95% CI 1.31-2.88, respectively). Compared with men doing mentally demanding jobs, service workers/salesperson and retired men were more prone to UI (AOR 2.67, 95% CI 1.14-6.36 and AOR 2.41, 95% CI 1.19-4.87, respectively). Further analysis showed that the associations of economic hardship with UI were attenuated when adjusting for access to healthcare. CONCLUSION: No formal education in women and severe economic hardship in both the sexes were associated with an increased risk of UI among middle-aged and older persons. The disparities should be taken into account in interventions for prevention, treatment and management of UI. Geriatr Gerontol Int 2021; 21: 245-253.