Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Neurol Sci ; 45(6): 2661-2670, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38183553

RESUMO

INTRODUCTION: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. METHODS: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. RESULTS: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. CONCLUSION: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.


Assuntos
Antiparkinsonianos , Estudos de Viabilidade , Levodopa , Transtornos Parkinsonianos , Humanos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Levodopa/farmacologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Fenômenos Biomecânicos/fisiologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/diagnóstico , Índice de Gravidade de Doença
2.
Opt Express ; 31(2): 2467-2479, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785260

RESUMO

A weakly-coupled few mode fiber (FMF) with a simple double-layer core is designed and fabricated that support five (seven) weakly coupled mode groups with average attenuation of 0.21 dB/km (0.39 dB/km) at the C + L (O) optical wavelength bands. Two data transmission experiments are demonstrated utilizing the fiber. A 2-km orbital angular momentum (OAM) mode-group multiplexing (MGM) experiment in the O band achieves error-free transmission for all five multiplexed mode groups without multiple multiple-input multiple-output (MIMO) processing. A 40-km OAM mode division multiplexing (MDM) experiment supporting 14 mode channels in the C + L bands achieves bit error rates (BER) of below 2.4 × 10-2 (20% soft-decision forward-error-correction threshold) for all channels, based on low-complexity 4 × 4 or 2 × 2 MIMO equalization. These demonstrations prove the capability of the fiber to support weakly coupled MDM/MGM transmission across O + C + L optical wavelength bands.

3.
Aging Clin Exp Res ; 35(11): 2507-2516, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37639172

RESUMO

BACKGROUND: Frailty is common in Parkinson's disease (PD) and increases vulnerability to adverse outcomes. Early detection of this syndrome aids in early intervention. AIMS: To objectively identify frailty at an early stage during routine motor tasks in PD patients using a Kinect-based system. METHODS: PD patients were recruited and assessed with the Fried criteria to determine their frailty status. Each participant was recorded performing the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) extremity tasks with a Kinect-based system. Statistically significant kinematic parameters were selected to discriminate the pre-frail from the non-frail group. RESULTS: Of the fifty-two participants, twenty were non-frail and thirty-two were pre-frail. Decreased frequency in finger tapping (P = 0.005), hand grasping (P = 0.002), toe tapping (P = 0.002), and leg agility (P = 0.019) alongside reduced hand grasping speed (P = 0.030), lifting (P < 0.001) and falling speed (P < 0.001) in leg agility were observed in the pre-frail group. Amplitude in leg agility (P = 0.048) and amplitude decrement rate (P = 0.046) in hand grasping showed marginally significant differences between two groups. Moderate discriminative values were found in frequency and speed of the extremity tasks to identify pre-frailty with sensitivity, specificity, and area under the curve (AUC) in the range of 45.00-85.00%, 68.75-100%, and 0.701-0.836, respectively. The combination of frequency and speed in extremity tasks showed moderate to high discriminatory ability, with AUC of 0.775 (95% CI 0.637-0.913, P < 0.001) for upper limb tasks and 0.909 (95% CI 0.832-0.987, P < 0.001) for lower limb tasks. When combining these features in both upper and lower limb tasks, the AUC increased to 0.942 (95% CI 0.886-0.999, P < 0.001). CONCLUSIONS: Our findings demonstrated the promise of utilizing Kinect-based kinematic data from MDS-UPDRS III tasks as early indicators of frailty in PD patients.


Assuntos
Fragilidade , Doença de Parkinson , Humanos , Extremidade Inferior , Mãos , Extremidade Superior
4.
Opt Express ; 30(11): 18199-18207, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36221626

RESUMO

A successful transmission of 14 multiplexed orbital angular momentum (OAM) channels each carrying 80 wavelengths over a 100-km single-span ring-core fiber (RCF) is experimentally demonstrated. Each transmission channel is modulated by a 20-GBaud quadrature phase-shift keying (QPSK) signal, achieving a record spectral-efficiency-distance product of 1870 (bit/s/Hz)·km for the single-core RCF based mode division multiplexing (MDM) transmissions. In addition, only low-complexity 2×2 or 4×4 multiple-input multiple-output (MIMO) equalization with time-domain equalization tap number no more than 25 is required to deal with the crosstalk among the highly degenerate intra-MG modes at the receiving end of the demonstrated OAM-MDM-WDM system, showing great potential in large-capacity and relatively long-distance MDM transmission with low digital signal processing (DSP) complexity.

5.
Ecotoxicol Environ Saf ; 192: 110246, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32028153

RESUMO

The thermal processes of cement kilns are sources of polybrominated dibenzofurans and dioxins (PBDD/Fs); however, when co-processing decabromodiphenyl ether (BDE-209) soil in cement kilns, very few reports have investigated the mechanism of PBDD/Fs formation from BDE-209. Therefore, the pathways and factors that influence the formation of PBDD/Fs were investigated using Box-Behnken design (BBD) of the response surface methodology (RSM) at lab-scale. The PBDEs, HBr/Br2 and PBDD/Fs emissions in flue gas from the simulated thermal process were analyzed using gas chromatography/mass spectroscopy (GC/MS), high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS), and ion chromatography (IC). Density functional theory (DFT) was also used to further discuss the formation of PBDD/Fs. The major products of BDE-209 thermal decomposition in flue gas were 97.1% HBr/Br2 (a.v. 26.6%/70.6%) > 2.7% PBDEs >0.2% PBDD/Fs. Formation of precursors were the main pathways for PBDD/Fs, and those precursors were dominated by higher-brominated PBDEs (heptã deca-BDEs); debromination of BDE-209 was also a crucial pathway for the formation of PBDD/Fs throughout the thermal process. Interestingly, it was easier to form HpBDD/Fs from OBDD/Fs than from PBDEs. The O2 percentage and interaction factors of O2 percentage, temperature, and CaCO3 percentage have the largest influence on PBDD/Fs emissions and formation.


Assuntos
Dibenzofuranos/metabolismo , Dioxinas/metabolismo , Éteres Difenil Halogenados/metabolismo , Hidrocarbonetos Bromados/metabolismo , Poluentes do Solo/metabolismo , Materiais de Construção , Monitoramento Ambiental
6.
Environ Sci Technol ; 53(11): 6529-6538, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31099564

RESUMO

Information on placental transfer and adverse outcomes of short-chain per- and polyfluoroalkyl substance (PFASs) is limited, and factors responsible for PFAS placental transfer are still unclear. In the present study, concentrations of 21 PFASs were analyzed in 132 paired maternal and cord serum samples collected from residents in Beijing, China, and the placental transfer efficiency (PTE) of each PFAS was calculated. PTEs of short-chain perfluoroalkyl acids (PFAAs), including PFBA (146%), PFBS (97%), PFPeA (118%), and PFHxA (110%), were first reported, and a complete U-shaped trend of PTEs from C4 to C13 of perfluoroalkyl carboxylic acids (PFCAs) was obtained. Positive association between maternal weight and PTE of perfluorooctanesulfonate (PFOS) ( p < 0.05) and negative association between maternal PFBA concentration and birth length ( p < 0.01) were observed. Using in vitro experiments, we further determined equilibrium dissociation constants ( Kds) of human serum albumin (HSA)-PFAS complexes ( Kd-HP), serum proteins-PFAS complexes ( Kd-SP), and liver-fatty acid binding protein (L-FABP)-PFAS complexes ( Kd-LP) and found that they were all significantly correlated with PTEs of PFASs. The correlation coefficient was 0.92, 0.89, and 0.86, respectively ( p < 0.01 in all three tests), suggesting that Kds of protein (serum)-PFAS complexes can play an important role in trans-placental transfer of PFASs in human and Kd-HP plays a pivotal role.


Assuntos
Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Pequim , Proteínas Sanguíneas , China , Feminino , Humanos , Gravidez
7.
Brain Behav Immun ; 45: 157-70, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25476600

RESUMO

Classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) macrophages populate the local microenvironment after spinal cord injury (SCI). The former type is neurotoxic while the latter has positive effects on neuroregeneration and is less toxic. In addition, while the M1 macrophage response is rapidly induced and sustained, M2 induction is transient. A promising strategy for the repair of SCI is to increase the fraction of M2 cells and prolong their residence time. This study investigated the effect of M2 macrophages induced from bone marrow-derived macrophages on the local microenvironment and their possible role in neuroprotection after SCI. M2 macrophages produced anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor ß and infiltrated into the injured spinal cord, stimulated M2 and helper T (Th)2 cells, and produced high levels of IL-10 and -13 at the site of injury. M2 cell transfer decreased spinal cord lesion volume and resulted in increased myelination of axons and preservation of neurons. This was accompanied by significant locomotor improvement as revealed by Basso, Beattie and Bresnahan locomotor rating scale, grid walk and footprint analyses. These results indicate that M2 adoptive transfer has beneficial effects for the injured spinal cord, in which the increased number of M2 macrophages causes a shift in the immunological response from Th1- to Th2-dominated through the production of anti-inflammatory cytokines, which in turn induces the polarization of local microglia and/or macrophages to the M2 subtype, and creates a local microenvironment that is conducive to the rescue of residual myelin and neurons and preservation of neuronal function.


Assuntos
Transferência Adotiva , Locomoção , Macrófagos/imunologia , Recuperação de Função Fisiológica/imunologia , Traumatismos da Medula Espinal/imunologia , Animais , Axônios/metabolismo , Axônios/patologia , Feminino , Inflamação , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/transplante , Microglia/imunologia , Microglia/metabolismo , Bainha de Mielina/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Células Th2/imunologia , Fator de Crescimento Transformador beta/imunologia , Fator de Necrose Tumoral alfa
8.
Exp Gerontol ; 171: 112037, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36436758

RESUMO

BACKGROUND: The excessive activation of the microglia leads to the release of inflammatory factors that contribute to neuronal cell loss and neurodegeneration in Parkinson's Disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) that belongs to a newly found neurotrophic factors (NTFs) family has been reported to promote neuronal survival in the PD models. However, the effects of the MANF on neuroinflammation in PD remain unclear. METHODS: AAV8-MANF virus was constructed to determine whether the high expression of MANF can protect the neuroinflammation-induced dopaminergic neurodegeneration in rats with 6-OHDA-induced PD. Rotarod performance test, immunofluorescent staining and western bolt were employed to evaluate the behavioral dysfunction, dopaminergic neurodegeneration, microglia activation, and signal activation. 6-OHDA treated SH-SY5Y cells and LPS treated BV-2 cells were used as the in vitro model for MANF neuroprotective and neuroinflammation mechanisms. Cell vitality and apoptosis were evaluated with MTT, CCK-8 and flow cytometric analysis. The AKT/GSK3ß-Nrf2 signaling and the TNF-α/IL6 expression were measured by Western Blot. RESULTS: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3ß, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK3ß, and p-NF-κß level. CONCLUSIONS: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK3ß-Nrf-2 signaling axis.


Assuntos
Neuroblastoma , Doença de Parkinson , Humanos , Ratos , Animais , Fator de Necrose Tumoral alfa , Fatores de Crescimento Neural/farmacologia , Oxidopamina , Dopamina/metabolismo , Neurônios Dopaminérgicos
9.
Digit Health ; 9: 20552076231176653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223774

RESUMO

Objective: To quantify bradykinesia in Parkinson's disease (PD) with a Kinect depth camera-based motion analysis system and to compare PD and healthy control (HC) subjects. Methods: Fifty PD patients and twenty-five HCs were recruited. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was used to evaluate the motor symptoms of PD. Kinematic features of five bradykinesia-related motor tasks were collected using Kinect depth camera. Then, kinematic features were correlated with the clinical scales and compared between groups. Results: Significant correlations were found between kinematic features and clinical scales (P < 0.05). Compared with HCs, PD patients exhibited a significant decrease in the frequency of finger tapping (P < 0.001), hand movement (P < 0.001), hand pronation-supination movements (P = 0.005), and leg agility (P = 0.003). Meanwhile, PD patients had a significant decrease in the speed of hand movements (P = 0.003) and toe tapping (P < 0.001) compared with HCs. Several kinematic features exhibited potential diagnostic value in distinguishing PD from HCs with area under the curve (AUC) ranging from 0.684-0.894 (P < 0.05). Furthermore, the combination of motor tasks exhibited the best diagnostic value with the highest AUC of 0.955 (95% CI = 0.913-0.997, P < 0.001). Conclusion: The Kinect-based motion analysis system can be applied to evaluate bradykinesia in PD. Kinematic features can be used to differentiate PD patients from HCs and combining kinematic features from different motor tasks can significantly improve the diagnostic value.

10.
Front Aging Neurosci ; 14: 891644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813950

RESUMO

Background: Exercise plays an essential role in improving motor symptoms in Parkinson's disease (PD), but the underlying mechanism in the central nervous system remains unclear. Methods: Motor ability was observed after 12-week treadmill exercise on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. RNA-sequencing on four brain regions (cerebellum, cortex, substantia nigra (SN), and striatum) from control animals, MPTP-induced PD, and MPTP-induced PD model treated with exercise for 12 weeks were performed. Transcriptional networks on the four regions were further identified by an integrative network biology approach. Results: The 12-week treadmill exercise significantly improved the motor ability of an MPTP-induced mouse model of PD. RNA-seq analysis showed SN and striatum were remarkably different among individual region's response to exercise in the PD model. Especially, synaptic regulation pathways about axon guidance, synapse assembly, neurogenesis, synaptogenesis, transmitter transport-related pathway, and synaptic regulation genes, including Neurod2, Rtn4rl2, and Cd5, were upregulated in SN and striatum. Lastly, immunofluorescence staining revealed that exercise rescued the loss of TH+ synapses in the striatal region in PD mice, which validates the key role of synaptic regulation pathways in exercise-induced protective effects in vivo. Conclusion: SN and striatum are important brain regions in which critical transcriptional changes, such as in synaptic regulation pathways, occur after the exercise intervention on the PD model.

11.
Plant Sci ; 316: 111167, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35151451

RESUMO

Development after endo-dormancy release ensures perennial plants, such as forest trees, proper response to environmental changes and enhances their adaptability. In northern hemisphere, megasporophore and microsporophore of conifers undergo dormancy to complete their development. Here combined with transcriptome data, we used high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (ESI-HPLC-MS/MS) to quantitatively analyse the various hormones (Abscisic Acid (ABA), 3-Indoleacetic acid (IAA), Gibberellins (GAs), Cytokinin (CTK), Jasmonic acid (JA) and Salicylic acid (SA)) of Chinese pine (Pinus tabuliformis Carr.) male strobili after endo-dormancy release. More specifically, we analysed endogenous hormones and their related-genes and verified the important role of ABA in plants growth and development. We observed rapid decrease in ABA content after dormancy release, resulting in reducing the inhibitory effect on male strobili growth. Similarly, rapid drop in ABA/GA ratio was observed and was associated with the start of male strobili growth and development. Combined with transcriptome data, we found that HAB2-SnRK2.10 played a central role in the ABA pathway in the entire network of hormones regulating male strobili development. Due to external environment warming, the differentially expressed HAB2-SnRK gene led to ABA content rapid decline, thus initiating male strobili growth. We constructed a network of hormone-regulated development to understand the interactions between hormones after male strobili dormancy release of male strobili. This study provided essential foundations for studying megasporophore and microsporophore growth mechanism after endo-dormancy and offered new ideas for flower development in gymnosperms and angiosperms.


Assuntos
Pinus , Reguladores de Crescimento de Plantas , Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Giberelinas , Pinus/metabolismo , Cone de Plantas , Dormência de Plantas , Proteínas de Plantas/metabolismo , Espectrometria de Massas em Tandem , Transcriptoma
12.
Plant Sci ; 323: 111383, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35850285

RESUMO

It is well documented that the CO/NF-YB/NF-YC trimer (NF-Y-CO) binds and regulates the FT promoter. However, the FT/TFL1-like (FLOWERING LOCUS T/TERMINALFLOWER1-like) genes in gymnosperms are all flowering suppressors, and the regulation model of NF-Y in gymnosperms is different from that in angiosperms. Here, using Chinese pine (Pinus tabuliformis), we identified a CONSTANS-LIKE gene, PtCOL5, the expression of which was strongly induced during cones development and it functioned as a repressor of flowering. PtNF-YC4, which interacted with PtCOL5, was highly correlated with PtCOL5 during growth and development, has been demonstrated. Moreover, PtNF-YC4 and PtCOL5 can bind to PtTFL2 promoter, and their interaction can enhance PtTFL2 expression. Interestingly, we found PtNF-YC4 and PtCOL5 were involved in gibberellin signaling and their interaction was inhibited by PtDELLA protein, thus affecting PtTFL2 expression. Collectively, PtCOL5-PtNF-YC4 was involved in reproductive cone development and gibberellin signaling in Chinese pine. Our findings uncovered reproductive cone development and signal transduction mechanism of COL-NF-Y in gymnosperms.


Assuntos
Regulação da Expressão Gênica de Plantas , Pinus , China , Flores/genética , Giberelinas , Pinus/genética , Pinus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transdução de Sinais
13.
Light Sci Appl ; 11(1): 202, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35790720

RESUMO

Space-division multiplexing (SDM), as a main candidate for future ultra-high capacity fibre-optic communications, needs to address limitations to its scalability imposed by computation-intensive multi-input multi-output (MIMO) digital signal processing (DSP) required to eliminate the crosstalk caused by optical coupling between multiplexed spatial channels. By exploiting the unique propagation characteristics of orbital angular momentum (OAM) modes in ring core fibres (RCFs), a system that combines SDM and C + L band dense wavelength-division multiplexing (DWDM) in a 34 km 7-core RCF is demonstrated to transport a total of 24960 channels with a raw (net) capacity of 1.223 (1.02) Peta-bit s-1 (Pbps) and a spectral efficiency of 156.8 (130.7) bit s-1 Hz-1. Remarkably for such a high channel count, the system only uses fixed-size 4 × 4 MIMO DSP modules with no more than 25 time-domain taps. Such ultra-low MIMO complexity is enabled by the simultaneous weak coupling among fibre cores and amongst non-degenerate OAM mode groups within each core that have a fixed number of 4 modes. These results take the capacity of OAM-based fibre-optic communications links over the 1 Pbps milestone for the first time. They also simultaneously represent the lowest MIMO complexity and the 2nd smallest fibre cladding diameter amongst reported few-mode multicore-fibre (FM-MCF) SDM systems of >1 Pbps capacity. We believe these results represent a major step forward in SDM transmission, as they manifest the significant potentials for further up-scaling the capacity per optical fibre whilst keeping MIMO processing to an ultra-low complexity level and in a modularly expandable fashion.

14.
Oxid Med Cell Longev ; 2022: 7925686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847585

RESUMO

Progressive accumulation of misfolded SNCA/α-synuclein is key to the pathology of Parkinson's disease (PD). Drugs aiming at degrading SNCA may be an efficient therapeutic strategy for PD. Our previous study showed that mesencephalic astrocyte-derived neurotrophic factor (MANF) facilitated the removal of misfolded SNCA and rescued dopaminergic (DA) neurons, but the underlying mechanisms remain unknown. In this study, we showed that AAV8-MANF relieved Parkinsonian behavior in rotenone-induced PD model and reduced SNCA accumulation in the substantia nigra. By establishing wildtype (WT) SNCA overexpression cellular model, we found that chaperone-mediated-autophagy (CMA) and macroautophagy were both participated in MANF-mediated degradation of SNCAWT. Nuclear factor erythroid 2-related factor (Nrf2) was activated to stimulating macroautophagy activity when CMA pathway was impaired. Using A53T mutant SNCA overexpression cellular model to mimic CMA dysfunction situation, we concluded that macroautophagy rather than CMA was responsible to the degradation of SNCAA53T, and this degradation was mediated by Nrf2 activation. Hence, our findings suggested that MANF has potential therapeutic value for PD. Nrf2 and its role in MANF-mediated degradation may provide new sights that target degradation pathways to counteract SNCA pathology in PD.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Autofagia/fisiologia , Neurônios Dopaminérgicos/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fatores de Crescimento Neural/metabolismo , Doença de Parkinson/tratamento farmacológico , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
15.
Front Aging Neurosci ; 14: 1066331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36711204

RESUMO

Background: Decreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson's disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well. Purpose: To evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD). Methods: Thirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios. Results: The combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively. Conclusion: 131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

16.
Se Pu ; 39(5): 541-551, 2021 May.
Artigo em Zh | MEDLINE | ID: mdl-34227339

RESUMO

A method for the determination of 25 organochlorine pesticides (OCPs) in the atmosphere using isotope dilution high-resolution gas chromatography/high-resolution mass spectrometry (ID-HRGC/HRMS) was developed. Sample extraction was performed using an accelerated solvent extractor (ASE). The extraction parameters were as follows: the extraction solvent was 50% (v/v) hexane in dichloromethane, the extraction temperature was 100 ℃, the static time was 8 min, the cell was rinsed with 60% cell volume using the aforementioned extraction solvent, the purging time was 180 s with N2 gas, and the extraction proceeded through three cycles. The eluting solutions of common cartridges such as florisil, graphitized carbon black, alumina, and silica were determined via cartridge elution tests. Use of the aforementioned cartridges alone cannot remove the pigments in the air sample solution. Subsequently, all possible pairwise combinations of the four cartridges were used for sample cleaning, and only the combination of florisil and graphitized carbon black was found to completely remove the pigments. Thus, the combination of florisil and graphitized carbon black cartridges using 10 mL toluene for elution was determined as the final cleaning method in this study. A high-resolution mass spectrometer equipped with a gas chromatograph was used for quantification. A fused-silica capillary column (Rtx-CL Pesticides2, 30 m×0.25 mm×0.2 µm) was used to separate the target compounds. Injection was performed in the splitless mode at 250 ℃. The flow rate of nitrogen gas was maintained constant at 1 mL/min. The oven temperature was 110 ℃ (1 min), 20 ℃/min up to 210 ℃, 1.5 ℃/min up to 218 ℃ (1 min), and 2 ℃/min up to 260 ℃ (1 min). HRMS was conducted at >8000 resolution, the source temperature was 280 ℃ in the electron impact mode using ionization energy of 35 eV, and measurements were performed in the selective ion monitoring (SIM) mode. Twenty-five OCPs were identified by comparing their GC retention times with those of the corresponding labeled compounds, and the actual ion abundance ratios of two exact m/z values with the corresponding theoretical values. The 25 OCPs were quantified by average relative response factors (RRFs), and the relative standard deviations (RSDs) of the RRFs with six calibration solutions were no more than 20%. The linear range of this method was 0.4 to 800 µg/L, and the correlation coefficients (R2) were higher than 0.992. To validate the method, clean materials (one quartz fiber filter (QFF) and two polyurethane foam (PUF) plugs) were spiked with 100 pg, 400 pg, and 15 ng native OCP standards, respectively; the RSDs of the 25 OCPs for each spiked level ranged from 0.64% to 16%. The spiking recoveries of the native OCPs ranged from 67.2% to 135%. Penetration experiments were conducted by sampling various volumes of air (15-1000 m3) using a filter-PUF/PUF high-volume active sampler. The breakthrough volume was sampled when the amount of OCPs collected in the PUF of the non-sampling end reached 5% of the total amount collected by both PUFs. When a high-volume active sampler with filter-PUF/PUF was used as an adsorbent for sampling atmospheric OCPs, a serious breakthrough of pentachlorobenzene (PeCB) occurred. The effective sampling volume of hexachlorobenzene (HCB) was very low, and was no more than 30 m3 under the standard conditions (101.325 kPa, 273 K). The effective sampling volumes of other OCP compounds should be no more than 1200 m3. This will necessitate the use of high-adsorption-capacity adsorbents such as the PUF-XAD (a styrene-divinylbenzene copolymer) sandwich used for sampling air PeCB and HCB. Calculation with the effective sampling volumes from the penetration experiment revealed that the limits of detection of the 25 OCPs were in the range of 0.002 to 0.7 pg/m3. Thus, the detection levels of OCPs in this study were reduced to at least 2% of the current monitoring standards. Analysis of air samples in Beijing showed that all the target compounds except for trans-heptachlor epoxide, endrin, cis-nonachlor and 4,4'-DDD were 100% detected in the air samples. The concentrations of HCB (in volumes of 15-30 m3) ranged from 514 to 563 pg/m3, while those of the other OCPs (in a volume of 600 m3) ranged from 0.01 to 18.9 pg/m3. The recoveries of surrogate standards in this sample analysis were in the range of 33.9% to 155%, which satisfied the requirements of EPA Method 1699. Because of the very high detection limits, the current related monitoring standards cannot meet the requirements of atmospheric OCP analysis, especially at the ultra-trace level. In addition, highly sensitive monitoring standard methods are urgently needed. This method is suitable for analyzing most atmospheric OCPs, even at the ultra-trace level. It also lays the foundation for a new standard method formulation and provides strong support for the implementation of relevant international conventions.

17.
Oxid Med Cell Longev ; 2020: 8951907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566108

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the formation of intracellular Lewy bodies (LB) in the brain, which aggregates α-synuclein (α-Syn) as the main component. The interest of flavonoids as potential neuroprotective agents is increasing due to its high efficiency and low side effects. Baicalin is one of the flavonoid compounds, which is a predominant flavonoid isolated from Scutellaria baicalensis Georgi. However, the key molecular mechanism by which Baicalin can prevent the PD pathogenesis remains unclear. In this study, we used bioinformatic assessment including Gene Ontology (GO) to elucidate the correlation between oxidative stress and PD pathogenesis. RNA-Seq methods were used to examine the global expression profiles of noncoding RNAs and found that C/EBPß expression was upregulated in PD patients compared with healthy controls. Interestingly, Baicalin could protect DA neurons against reactive oxygen species (ROS) and decreased C/EBPß and α-synuclein expression in pLVX-Tet3G-α-synuclein SH-SY5Y cells. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model, the results revealed that treatment with Baicalin improved the PD model's behavioral performance and reduced dopaminergic neuron loss in the substantia nigra, associated with the inactivation of proinflammatory cytokines and oxidative stress. Hence, our study supported that Baicalin repressed C/EBPß via redox homeostasis, which may be an effective potential treatment for PD.


Assuntos
Antioxidantes/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Flavonoides/farmacologia , Doença de Parkinson/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Linhagem Celular , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Flavonoides/química , Ontologia Genética , Humanos , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Anotação de Sequência Molecular , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Neurotoxinas/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/metabolismo
18.
RSC Adv ; 9(52): 30503-30508, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-35530248

RESUMO

Liquid crystal (LC) smart windows with adjustable reflectivity have been gradually applied in green and intelligent building materials for energy saving needs, but their applications are limited by their fundamental defects. In this study, we developed local photo-induced in situ polymerization to rapidly fabricate the infrared reflection microsheets of a cholesteric LC polymer as functional units. With the exception of the LC formula, the photo mask, liquid crystal cell, polymerization inhibitor, and the preparation conditions were specifically managed to control the extent of in situ polymerization, namely the microsheet morphology. The circular, triangular and oval-shaped microsheets were precisely obtained and were slightly bigger than the light hole. This easy, controllable, continuous and recyclable technology is expected to promote the industrialization of a high quality LC smart window with an adjustable reflection band and state.

19.
Am J Transl Res ; 10(5): 1284-1294, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887945

RESUMO

OBJECTIVE: This study aimed to investigate the therapeutic effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the MPTP/MPP+-induced model of Parkinson's disease (PD) and the potential mechanism. METHODS: Male C57BL/6 mice PD model with MPTP-induced were randomly injected bilaterally with MANF or PBS into the striatum. Two weeks later, Rotarod test, immunohistochemistry, and detection of dopamine (DA) and its metabolites, superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were performed. A cell model of PD was established by incubating SH-SY5Y cells with MPP+, cells were pretreated for 2 h with different concentrations of MANF before 24 h incubation with MPP+. Cell viability, expression of Bax, and Bcl-2, gene expression levels of Heme oxygenase 1 (HMOX1) and Superoxide dismutase 2 (SOD2), and mitochondrial transmembrane potential were detected. RESULTS: The latency reduction in PD mice was partially restored after MANF treatment (P<0.05); MANF significantly reduced the loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) (P<0.01); MANF significantly increased the striatal DA level in PD mice (P<0.05) and markedly increased the SOD activity (P<0.01) and GSH production (P<0.01). MANF pre-treatment significantly decreased the MPP+-induced reduction of cell viability (P<0.01), inhibited the ratio of Bax/Bcl-2 expression (P<0.01), activated gene expression levels of HMOX1 (P<0.01) and SOD2 (P<0.05), and reversed MPP+-induced loss of mitochondrial membrane potential (P<0.01). CONCLUSION: MANF can attenuate the neuronal lesion in MPTP/MPP+-induced PD mice, which may be related to the improvement of mitochondrial function and inhibition of oxidative stress.

20.
Oncotarget ; 8(40): 67837-67850, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28978077

RESUMO

The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus. The mRNA expression analysis further demonstrated that AM1241 increased expression of the CB2R and activated Parkin/PINK1 signaling pathways. Furthermore, the increased number of TH-positive cells in the substantia nigra indicated that AM1241 regenerated DA neurons in PD mice, and could therefore be a potential candidate for PD treatment. The clear co-localization of CB2R and DA neurons suggested that AM1241 targeted CB2R, thus also identifying a novel target for PD treatment. In conclusion, the selective CB2 agonist AM1241 has a significant therapeutic effect on PD mice and resulted in regeneration of DA neurons following MPTP-induced neurotoxicity. The possible mechanisms underlying the neurogenesis effect of AM1241 might be the induction of CB2R expression and an increase in phosphorylation of the PI3K/AKT signaling pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA