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1.
Mol Neurobiol ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984583

RESUMO

Parkinson's disease (PD) is an incurable neurodegenerative disease characterized by aggregation of pathological alpha-synuclein (α-syn) and loss of dopaminergic neuron in the substantia nigra. Inhibition of phosphorylation of the α-syn has been shown to mediate alleviation of PD-related pathology. Protein phosphatase 2A (PP2A), an important serine/threonine phosphatase, plays an essential role in catalyzing dephosphorylation of the α-syn. Here, we identified and validated cancerous inhibitor of PP2A (CIP2A), as a potential diagnostic biomarker for PD. Our data showed that plasma CIP2A concentrations in PD patients were significantly lower compared to age- and sex-matched controls, 1.721 (1.435-2.428) ng/ml vs 3.051(2.36-5.475) ng/ml, p < 0.0001. The area under the curve of the plasma CIP2A in distinguishing PD from the age- and sex-matched controls was 0.776. In addition, we evaluated the role of CIP2A in PD-related pathogenesis in PD cellular and MPTP-induced mouse model. The results demonstrated that CIP2A is upregulated in PD cellular and MPTP-induced mouse models. Besides, suppression of the CIP2A expression alleviates rotenone induced aggregation of the α-syn as well as phosphorylation of the α-syn in SH-SY5Y cells, which is associated with increased PP2A activity. Taken together, our data demonstrated that CIP2A plays an essential role in the mechanisms related to PD development and might be a novel PD biomarker.

2.
Brain Imaging Behav ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34988779

RESUMO

To advance the understanding of the dynamic relationship between brain activities and emotional experiences, we examined the neural patterns of tension, a unique emotion that highly depends on how an event unfolds. Specifically, the present study explored the temporal relationship between functional connectivity patterns within and between different brain functional modules and the fluctuation in tension during film watching. Due to the highly contextualized and time-varying nature of tension, we expected that multiple neural networks would be involved in the dynamic tension experience. Using the neuroimaging data of 546 participants, we conducted a dynamic brain analysis to identify the intra- and inter-module functional connectivity patterns that are significantly correlated with the fluctuation of tension over time. The results showed that the inter-module connectivity of cingulo-opercular network, fronto-parietal network, and default mode network is involved in the dynamic experience of tension. These findings demonstrate a close relationship between brain functional connectivity patterns and emotional dynamics, which supports the importance of functional connectivity dynamics in understanding our cognitive and emotional processes.

3.
Immunol Invest ; : 1-13, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023444

RESUMO

The microRNA miR-30a has been reported to mitigate podocyte damage and resist injurious factors in lupus nephritis (LN), but the precise molecular mechanisms underlying these effects remain elusive. We hypothesized that miR-30a can ameliorate podocyte injury by downregulating the Notch1 signaling pathway and investigated the role of miR-30a in the pathogenesis of podocyte-treated with Immunoglobulin G from patients with LN (IgG-LN). The study enrolled 30 patients from new-onset systemic lupus erythematosus and 28 healthy individuals, then evaluated the levels of their serum miR-30a using RT-qPCR. Additionally, MPC5 cells were transfected with NICD-vector to overexpress Notch1, then with miR-30a mimics or inhibitors to determine miR-30a effects on Notch1. Analysis of function and regulatory mechanisms were performed with RT-qPCR, Western blotting, and CCK8 assays. Furthermore, we verified the candidate sequence targeted by miR-30a using a luciferase reporter gene assay. We observed a significant decrease in the serum miR-30a levels in patients with LN. Also, in IgG-LN-treated podocytes, miR-30a decreased and Notch1 expression was elevated. Bioinformatic analysis and transfection experiments revealed that Notch1 is a direct target of miR-30a. Further supporting this finding, miR-30a upregulation appeared to alleviate IgG-LN-treated podocyte injury, and Notch1 overexpression reversed this effect. To conclude, miR-30a can ameliorate podocyte injury via suppression of the Notch1 signaling pathway.

4.
Front Psychol ; 12: 746871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594287

RESUMO

The emergent respect for the prominence of engagement in the present education has made it one of the most widespread inquiry issues that it has been regarded as the ultimate target of learning. In the language teaching field, the idea of student activities for learning is intensely rooted in the prevailing standards of effective language learning, which considers language communication and interaction as analytical for language improvement. Moreover, teachers as center of learning process is the most prominent research attention, and teachers play a key role in regulating the education process as well as students' learning achievement. However, there is an absence of research which have considered teachers' care and praise among all positive interpersonal behavior and its significant effect on students' engagement. So, the present review attempts to focus on teacher care and praise, and their effects on student engagement in EFL classrooms. Subsequently, some implications are presented to clarify the practice of teachers, students, teacher educators, and materials developers.

5.
Front Immunol ; 12: 719807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691027

RESUMO

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson's disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.

6.
Front Aging Neurosci ; 13: 657095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393753

RESUMO

The pathogenesis of Parkinson's disease (PD) is currently unclear. Recent studies have suggested a correlation between vitamin D and PD. Vitamin D and its analogs have protective effects in animal models of PD, but these studies have not clarified the mechanism. Parthanatos is a distinct type of cell death caused by excessive activation of poly (ADP-ribose) polymerase-1 (PARP1), and the activation of PARP1 in PD models suggests that parthanatos may exist in PD pathophysiology. 1,25-Dihydroxyvitamin D3 (calcitriol) is a potential inhibitor of PARP1 in macrophages. This study aimed to investigate whether calcitriol treatment improves PD models and its effects on the parthanatos pathway. A 1-methyl-4-phenylpyridinium (MPP+)-induced cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute animal model were selected as the in vitro and in vivo PD models, and calcitriol was applied in these models. Results showed that parthanatos existed in the MPP+-induced cell model and pretreatment with calcitriol improved cell viability, reduced the excessive activation of PARP1, and relieved parthanatos. The application of calcitriol in the MPTP subacute animal model also improved behavioral tests, restored the damage to dopamine neurons, and reduced the activation of PARP1-related signaling pathways. To verify whether calcitriol interacts with PARP1 through its vitamin D receptor (VDR), siRNA, and overexpression plasmids were used to downregulate or overexpress VDR. Following the downregulation of VDR, the expression and activation of PARP1 increased and PARP1 was inhibited when VDR was overexpressed. Coimmunoprecipitation verified the combination of VDR and PARP1. In short, calcitriol can substantially improve parthanatos in the MPP+-induced cell model and MPTP model, and the protective effect might be partly through the VDR/PARP1 pathway, which provides a new possibility for the treatment of PD.

7.
Brain ; 144(7): 2024-2037, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-33792662

RESUMO

Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson's disease. Cell-to-cell propagation of α-synuclein pathology is a highlighted feature of Parkinson's disease, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-synuclein pathology. Recent data revealed that plasma exosomes derived from Parkinson's disease patients (PD-EXO) carry pathological α-synuclein and target microglia preferentially. Hence, PD-EXO are likely a key tool for investigating the role of microglia in α-synuclein transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-synuclein from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-synuclein and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-synuclein in the substantia nigra. Furthermore, exosomal α-synuclein internalization was initiated by binding to TLR2 of microglia. Excessive α-synuclein phagocytosis may induce the inflammatory responses of microglia and provide the seed for microglia-to-neuron transmission. Consistently, TLR2 silencing in microglia mitigated α-synuclein pathology in vivo. Overall, the present data support the idea that the interaction of exosomal α-synuclein and microglial TLR2 contribute to excessive α-synuclein phagocytosis and microglial activation, which lead to the further propagation and spread of α-synuclein pathology, thereby highlighting the pivotal roles of reactive microglia in α-synuclein transmission.


Assuntos
Exossomos/metabolismo , Microglia/metabolismo , Doença de Parkinson/metabolismo , Receptor 2 Toll-Like/metabolismo , alfa-Sinucleína/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley
8.
Sleep Med ; 75: 428-433, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32980664

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD). METHODS: We conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients. RESULTS: Compared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003). CONCLUSION: The findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.


Assuntos
Ansiedade/epidemiologia , COVID-19/psicologia , Depressão/epidemiologia , Pandemias , Doença de Parkinson/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Idoso , Estudos de Casos e Controles , China , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Pesquisa Qualitativa , Inquéritos e Questionários
9.
Front Neurol ; 10: 812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447756

RESUMO

A 47-year-old HIV-seronegative woman with autoimmune hemolytic anemia (AIHA) was treated with corticosteroids for 8 months. She developed central nervous system dysfunction and was diagnosed with cryptococcal meningitis (CM) after detecting cryptococcus neoformans in the cerebrospinal fluid. The patient's clinical symptoms were worsened and unusual MRI findings of white matter lesions were noticed even after adequate treatment, which were quite unusual compared with typical characteristics of CM. This led us to carry out further investigations. Similar cases have been reported previously in published literature. Combined with clinical symptoms and MRI findings, the most likely diagnosis was Cryptococcal Meningitis-Immune Reconstitution Inflammatory Syndrome. Unfortunately, the patient deteriorated and died of respiratory failure. Cryptococcal Meningitis-Immune Reconstitution Inflammatory Syndrome may have MRI changes during the early onset of the disease (bilateral basal ganglia). We propose that close monitoring of the condition, meticulous MRI follow-up and brain biopsies should be indicated in such cases for treating them actively, so as to avoid worsening of the patients' condition.

10.
Front Neurol ; 10: 271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949126

RESUMO

Although the pathogenic mechanisms of Parkinson's disease (PD) remain unclear, ample empirical evidence suggests that oxidative stress is involved in the pathogenesis of this disease. The nuclear factor E2-related factor 2 (Nrf2) is known to activate several antioxidant response element (ARE)-driven antioxidative genes that prevents oxidative stress in vitro and in vivo. Moreover, it was documented that hydralazine is a potent Nrf2 activator. In this study, we tested whether hydralazine can attenuate 1-Methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced neurotoxicity in vitro and in vivo by activating Nrf2 and its downstream network of antioxidative genes. We found that treatment with hydralazine attenuated MPP+ or H2O2-induced loss of cell viability in human neuroblastoma cell line (SH-SY5Y). In addition, hydralazine significantly promoted the nuclear translocation of Nrf2, and upregulated the expression of its downstream antioxidative genes. Further, knockout of Nrf2 abolished the protection conferred by hydralazine on MPP+ -induced cell death. Similar findings were observed in vivo. Before, during, and after MPTP 30 mg/kg (i.p.) administration for 7 days, the mice were given hydralazine (Hyd) 51.7 mg/kg per day by oral gavage for 3 weeks. Oral administration of hydralazine ameliorated oxidative stress, MPTP-induced behavioral disorder, and loss of neurons of dopaminergic system in the substantia nigra (SN) and striatum, all of which were attributed to its ability to activate the Nrf2-ARE pathway. Hydralazine increased the migration of Nrf2 to the nucleus in dopaminergic neurons, enhanced the expression of its downstream antioxidative genes. Together, these datasets show that the Nrf2-ARE pathway mediates the protective effects of hydralazine on Parkinson's disease.

11.
Front Neurol ; 10: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740086

RESUMO

Cluster headache is generally considered to be a primary headache; secondary cluster-like headache is quite rare, while cluster-like headache secondary to meningioma is even rarer. Here, we describe an unusual case with cluster-like headache 2.5 years after sphenoid ridge meningioma surgery. The cluster-like headache and meningioma were on the same side, and even at the same position. Furthermore, the cluster-like headache lasted for 6 months. In addition, the patient did not respond well to conventional treatments for cluster headache, such as oxygen inhalation, carbamazepine, and tramadol. Brain magnetic resonance imaging demonstrated a softening lesion, glial hyperplasia, and localized thickening and enhancement of the dura in the left frontal-temporal lobe. However, positron-emission computed tomography showed reduced metabolism in the left frontal-temporal lobe. Although the possibility of a primary headache cannot be completely eliminated, the association between cluster-like headache and probable tumor recurrence or postoperative changes should be considered.

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