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1.
Open Med (Wars) ; 16(1): 1444-1458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34632074

RESUMO

Objective: The purpose of this study was to explore the effect of CRABP2 and FABP5, and their ratio on prognosis in esophageal squamous cell carcinoma. Methods: The expression data of CRABP2 in esophageal cancer in TCGA and GEO were collected by the public database GEPIA. The expression levels of CRABP2 and FABP5 were examined using immunohistochemistry. The relationship between the two proteins and related clinicopathological parameters were analyzed by χ 2 test. Survival analysis was used to investigate the effect of CRABP2 and FABP5, and their ratio on prognosis. Results: Compared with normal esophageal mucosal epithelium, there was lower CRABP2 gene mRNA in the esophageal cancer tissue, and the difference was statistically significant (p < 0.01). For the expression level, no significant difference was observed in patients with stages I-IV in esophageal cancer. Immunohistochemistry showed that CRABP2 and FABP5 were both highly expressed in normal esophageal squamous epithelial cells at 100 and 94.1%, while lower in ESCC (75.6 and 58.7%). There was a significant difference in the expression between cancer and adjacent tissues (p < 0.001). No inherent relationship was manifested between the CRABP2 expression and the clinical parameters of the ESCC. The expression of FABP5 was related to lymph node metastasis (p = 0.032), the depth of invasion (p = 0.041), and the AJCC stage (p = 0.013). The ratio of CRABP2 and FABP5 was related to ethnicity (p = 0.001), nerve invasion (p = 0.031), and postoperative treatment (p = 0.038). CRABP2 is positively associated with FABP5 (r = 0.156, p = 0.041) and the ratio (r = 0.334, p = 0.000), while there was a negative correlation between FABP5 and the ratio (r = -0.269, p = 0.000). Patients with CRABP2-positive expression had a significantly longer overall survival than patients with CRABP2-negative expression (p = 0.025). Conclusion: CRABP2 as a suppressor factor is expected to be a potential prognosis marker for esophageal squamous cell carcinoma.

2.
Anal Chim Acta ; 1178: 338804, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482869

RESUMO

Gold nanoparticle (AuNP)-based colorimetric biosensors have been widely used for pH sensing and monitoring its changes. However, few AuNP-based pH sensors have been developed through the manipulation of the aggregation states of AuNPs via i-motif DNA. We herein report i-motif DNA-assisted pH-responsive gold nanoparticle assembly (termed RGA), which shows a reversible and highly sensitive response to pH variation between 6.20 and 7.40. The acidic pH triggers the disassembly of the RGA, thus converting the AuNPs from aggregation state to disperse state, which leads to a color transition from blue-purple to red. Therefore, the pH value can be estimated by naked-eye determination or UV-vis spectroscopy analysis. More significantly, the visually detectable color change is monitored using the built-in camera of a smartphone. The RGB (red, green, blue) values of the RGA solution are measured by a smartphone application (APP). Following data processing, the RGB values can be converted into pH value, providing a new strategy for the on-site and real-time pH sensing. Furthermore, the pH-induced conformation change of i-motif DNA allows the RGA to detect a slight pH fluctuation in the catalytic oxidation of glucose by glucose oxidase and the hydrolysis of urea by urease.


Assuntos
Ouro , Nanopartículas Metálicas , Colorimetria , Concentração de Íons de Hidrogênio , Smartphone
3.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443603

RESUMO

Abnormal levels of reduced glutathione (GSH) and glutathione reductase (GR) are usually related to a variety of diseases, so it is of great significance to determine the GSH concentration and GR activity. We herein develop a smartphone-assisted colorimetric biosensor for the detection of GSH and GR activity in human serum and mouse liver using hemin/G-quadruplex DNAzyme. Firstly, an obvious color change from colorless to green can be observed, owing to the high peroxidase-like activity of hemin/G-quadruplex DNAzyme toward 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) (ABTS). With the addition of GSH or GR, the H2O2-mediated oxidation of ABTS catalyzed by hemin/G-quadruplex DNAzyme is significantly inhibited, resulting in remarkable color fading. Therefore, the detection of GSH and GR activity can be achieved by observing the color transition or measuring the absorbance at 420 nm. The detection limit was estimated to be as low as 0.1 µM and 10 µU/mL for GSH and GR, respectively. More interestingly, the RGB values of the sensing system can be identified by the smartphone application (APP, color collect), which makes it an ideal format for on-site determination and point-of-care testing (POCT). In addition, the proposed method shows excellent selectivity and acceptable applicability for the determination of GSH concentration and GR activity in human serum samples and mouse liver tissues, which might hold great application potential in clinical diagnosis and drug screening.


Assuntos
Técnicas Biossensoriais/métodos , DNA Catalítico/metabolismo , Glutationa Redutase/sangue , Glutationa/sangue , Hemina/metabolismo , Fígado/metabolismo , Smartphone , Animais , Colorimetria , DNA Catalítico/química , Quadruplex G , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Camundongos , Oxirredução
4.
Sci Total Environ ; 798: 149191, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333431

RESUMO

Drinking water and groundwater treatment of perfluoroalkyl acids (PFAAs) heavily relies on adsorption-based approaches using carbonaceous materials, such as granular activated carbon (GAC). Application of GAC is restricted by its inefficiency to remove short-chain PFAAs that have prevalently emerged as substitutes and/or metabolites of long-chain polyfluoroalkyl and perfluoroalkyl substances (PFAS). Here, we synthesized reed straw-derived biochar (RESCA) exhibiting exceptional removal efficiencies (>92%) toward short-chain PFAAs at environment-relevant concentrations (e.g., 1 µg/L). Pseudo-second-order kinetic constants of RESCA were 1.13 and 1.23 L/(mg h) for perfluorobutanoic acid (PFBA) and perfluorobutanesulfonic acid (PFBS), respectively, over six times greater than GAC. SEM imaging and BET analysis revealed the combination of highly hydrophobic surface and scattered distribution of mesopores (2-10 nm in diameter) was associated with the rapid adsorption of short-chain PFAAs. RESCA-packed filters demonstrated effective removal of the mixture of three short-chain and three long-chain PFAAs in the influent with the flow rate up to 45 mL/min. In contrast, GAC-packed filters were significantly less efficient in the removal of short-chain PFAAs, which were also negatively affected by the increase of the flow rate. Efficacy of RESCA-packed filters was also validated in four PFAA-spiked groundwater samples from different sites. Dissolved organic matter (DOC) of >8 mg/L can negatively affect the removal of short-chain PFAAs by RESCA. Feasibility of scaling up the RESCA adsorption system was investigated using breakthrough simulation. Overall, RESCA represents a green adsorbent alternative for the feasible and scalable treatment of a wide spectrum of PFAAs of different chain lengths and functional moieties.


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , Fluorcarbonetos/análise , Poluentes Químicos da Água/análise
6.
Sci Total Environ ; 791: 148145, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119788

RESUMO

Microorganisms in activated sludge are widely recognized for their roles in wastewater treatment. However, previous studies were mainly concerned with the diversity and driving factors of microbial communities within domestic wastewater treatment, and those of domestic wastewater treatment systems mixed with industrial wastewater are poorly understood. In this research, three different full-scale aerobic activated sludge (AS) wastewater treatment systems fed with municipal, textile-dyeing, and mixed wastewater, respectively, were monitored over the operation course of three months. 16S rRNA amplicon sequencing analysis revealed that the microbial communities in textile-dyeing wastewater activated sludge (AS) exhibited significantly lower richness and diversity (p < 0.01, Adonis) compared to those fed with municipal wastewater. In contrast, textile-dyeing derived AS selectively enriched microbial taxa with aromatic degradation and denitrification potentials. Further, FARPROTAX and metabolomics indicated the inhibition of 72.5% metabolic functions (p < 0.01) in AS from the system fed with textile-dyeing wastewater, including the pathways of pentose phosphate metabolism, purine metabolism, and glycerophospholipid metabolism. Overall, this study corroborates textile-dyeing wastewater is a novel microbial niche and could suppress sludge performance by inhibiting microbial activity and metabolism, raising concerns on AS-based systems for industrial wastewater treatment.


Assuntos
Águas Residuárias , Purificação da Água , RNA Ribossômico 16S/genética , Esgotos , Têxteis , Eliminação de Resíduos Líquidos
8.
Exp Ther Med ; 22(1): 722, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34007331

RESUMO

Esophageal cancer has always been one of the major malignant tumor types affecting the health of the Chinese population. Metastasis-associated protein 1 (MTA1), SOX4 and enhancer of zeste homolog 2 (EZH2) are all potent inducers of invasion and metastasis in esophageal squamous cell carcinoma (ESCC). However, the role of these signaling molecules and their implication in ESCC have remained largely elusive. In the present study, the effects of MTA1, SOX4 and EZH2 on the prognosis of patients with ESCC were explored. Immunohistochemistry was used to examine the expression levels of MTA1, SOX4 and EZH2. The χ2 test was used to analyze the association between protein expression and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards model survival analysis was performed to investigate the effects of the three proteins examined on disease prognosis. The results indicated that MTA1 may be used as a prognostic and diagnostic marker for ESCC. To the best of our knowledge, the present study was the first to demonstrate that MTA1-SOX4 signaling is associated with prognosis in ESCC. However, no significant association was noted between SOX4 and EZH2 in the present study, which was inconsistent with previously reported findings. The function of the MTA1-SOX4-EZH2 axis and the interactions of the proteins involved require further investigation.

9.
Ecotoxicol Environ Saf ; 217: 112206, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33866286

RESUMO

1,4-Dioxane (dioxane), an emerging groundwater contaminant, is frequently detected in landfill leachates with its structural analog, tetrahydrofuran (THF). Along with undesirable leakage of landfill leachates, dioxane and THF inevitably percolate into groundwater leading to a broader region of contamination. Cometabolic bioremediation is an effective approach to manage commingled THF and dioxane pollution. In this study, a newly isolated bacterium Arthrobacter sp. WN18 is able to co-oxidize dioxane with THF as the primary substrate. Meanwhile, the THF-induced thmADBC gene cluster was responsible for the dioxane degradation rate indicating THF monooxygenase is the essential enzyme that initializing α-hydroxylation of THF and dioxane. Further, γ-butyrolactone and HEAA were characterized as the key metabolites of THF and dioxane, respectively. In addition, WN18 can tolerate the inhibition of trichloroethylene (5.0 mg/L) as a representative of co-existing leachate constituent, and sustain its activity at various pH (5-11), temperatures (15-42 °C), and salinities (up to 4%, as NaCl wt). Like other Arthrobacter species, WN18 also exhibited the capability of fixing nitrogen. All this evidence indicates the feasibility and advantage of WN18 as a thmADBC-catalyzed inoculator to bioremediate co-contamination of THF and dioxane.


Assuntos
Arthrobacter/metabolismo , Biodegradação Ambiental , Dioxanos/metabolismo , Furanos/metabolismo , Proteínas de Bactérias , Água Subterrânea , Oxigenases de Função Mista , Família Multigênica , Oxirredução , Tricloroetileno , Poluentes Químicos da Água
10.
Sci Total Environ ; 774: 145118, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-33610989

RESUMO

Chlorinated solvents, notably trichloroethene (TCE), and the cyclic ether stabilizer, 1,4-dioxane (dioxane), have been frequently detected commingling in contaminated aquifers. Here we developed a sequential anaerobic and aerobic treatment strategy effective to mitigate the co-contamination of TCE and dioxane, particularly when dioxane is present at ppb levels relevant to many impacted sites. After the primary anaerobic treatment by a halorespiring consortium SDC-9, TCE was effectively removed, though lingering less-chlorinated metabolites, vinyl chloride (VC) and cis-dichloroethene (cDCE). Subsequent aerobic bioaugmentation with Azoarcus sp. DD4, a cometabolic dioxane degrader, demonstrated the ability of DD4 to degrade dioxane at an initial concentration of 20 µg/L to below 0.4 µg/L and its dominance (~7%) in microcosms fed with propane. Even better, DD4 can also transform VC and cDCE in tandem, though cDCE and VC at relatively high concentrations (e.g., 1 mg/L) posed inhibition to propane assimilation and cell growth of DD4. Mutagenesis of DD4 revealed group-2 toluene monooxygenase and group-5 propane monooxygenase are responsible for cDCE and VC co-oxidation, respectively. Overall, we demonstrated the feasibility of a treatment train combining reductive dehalogenation and aerobic co-oxidation processes in tandem to not only effectively clean up prevalent co-contamination of TCE and dioxane at trace levels but also mitigate persistent products (e.g., cDCE and VC) when complete reductive dehalogenation of less-chlorinated ethenes occurs slowly in the field.


Assuntos
Água Subterrânea , Tricloroetileno , Poluentes Químicos da Água , Anaerobiose , Biodegradação Ambiental , Dicloroetilenos , Dioxanos
11.
Eur J Neurol ; 28(4): 1265-1274, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33277774

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). METHODS: We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver-operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects. RESULTS: Compared with the "good and sustained benefit" (GSB) outcome group (defined as ≥4-point reduction in National Institutes of Health Stroke Scale or a score of 0-1 at 24 h and 7 days) and the "good functional outcome" (GFO) group (modified Rankin Scale score 0-2 at 90 days), serum CysC baseline levels were increased in the non-GSB and non-GFO groups. Logistic regression analysis found that CysC was an independent negative prognostic factor for GSB (odds ratio [OR] 0.010; p = 0.005) and GFO (OR 0.011; p = 0.021) after adjustment for potential influencing factors. Receiver-operating characteristic curves showed the CysC-involved combined models provided credible efficacy for predicting post-90-day favorable clinical outcome (area under the curve 0.86; p < 0.001). CONCLUSIONS: Elevated serum CysC is independently associated with unfavorable clinical outcomes after IV-tPA therapy in AIS. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.

12.
Water Res ; 188: 116569, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142118

RESUMO

Intimately coupled photocatalysis and biodegradation (ICPB) combining photocatalysis with microbial degradation is an attractive wastewater treatment technology. However, when prepared in conventional ways, the supported-photocatalysts aggregate frequently, detach easily from carriers, and prohibit the colonization of microorganisms inside the carriers. To overcome these challenges, silane coupling agent (SCA)-enhanced TiO2 coating method is developed in this study. The coupling agent γ-glycidoxypropyltrimethoxysilane (KH560) greatly enhanced the adhesion between photocatalysts and the carrier through ether and Ti-O-Si linkages. The dense TiO2 layer was firmly adhered to the carrier outer surface, and the loading amount reached 351.8±8.2 mg/g, over ten times higher than using the powder sintering method (31.5±2.4 mg/g). In the ICPB system constructed with the KH560-enhanced TiO2-supported polyurethane sponge (KH560-TiO2-PU) carriers, removal efficiencies of two model odor substances, 2-methylisoborneol (2-MIB) and geosmin (GSM), reached 88.9±0.3% and 85.0±1.0% in 12 h at an initial concentration of 500 ng/L respectively, which were 17.7±0.6% and 19.4±0.4% greater than those of the ICPB system prepared with the powder sintering method. After 5 operating cycles, the novel ICPB system remained stable with high 2-MIB and GSM removal efficiencies, reaching 89.9±0.8% and 86.1±0.2% respectively after 12h, while TiO2 peeling ratio was as low as 5.0±2.8%. Biofilms attached onto the carrier inner surface were resilient over the operating cycles with the increase of both richness and diversity of microbial communities. Analysis of biofilm microbial community and pollutant degradation pathways revealed the enhanced removal of 2-MIB and GSM in the novel ICPB system might be attributed to multiple factors. First, the alleviated aggregation and increased adhesion of photocatalysts onto carriers improved the overall photocatalysis efficiency. Second, biofilm inside of the carrier was protected and the microbial activity was well remained. Third, photocatalytic intermediate products were efficiently biodegraded by the enriched functional microbial populations, such as Thauera and Flavobacterium, with little concern of excessive oxidation. Collectively, this research provides a new technological solution that synergizes photocatalysis and biodegradation for effective removal of odorous substances in polluted natural water.


Assuntos
Odorantes , Silanos , Biodegradação Ambiental , Titânio
13.
Front Aging Neurosci ; 12: 576682, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343329

RESUMO

Previous studies reported abnormal spontaneous neural activity in Parkinson's disease (PD) patients using resting-state functional magnetic resonance imaging (R-fMRI). However, the frequency-dependent neural activity in PD is largely unknown. Here, 35 PD patients and 35 age- and education-matched healthy controls (HCs) underwent R-fMRI scanning to investigate abnormal spontaneous neural activity of PD using the amplitude of low-frequency fluctuation (ALFF) approach within the conventional band (typical band: 0.01-0.08 Hz) and specific frequency bands (slow-5: 0.010-0.027 Hz and slow-4: 0.027-0.073 Hz). Compared with HCs, PD patients exhibited increased ALFF in the parieto-temporo-occipital regions, such as the bilateral inferior temporal gyrus/fusiform gyrus (ITG/FG) and left angular gyrus/posterior middle temporal gyrus (AG/pMTG), and displayed decreased ALFF in the left cerebellum, right precuneus, and left postcentral gyrus/supramarginal gyrus (PostC/SMG) in the typical band. PD patients showed greater increased ALFF in the left caudate/putamen, left anterior cingulate cortex/medial superior frontal gyrus (ACC/mSFG), left middle cingulate cortex (MCC), right ITG, and left hippocampus, along with greater decreased ALFF in the left pallidum in the slow-5 band, whereas greater increased ALFF in the left ITG/FG/hippocampus accompanied by greater decreased ALFF in the precentral gyrus/PostC was found in the slow-4 band (uncorrected). Additionally, the left caudate/putamen was positively correlated with levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) stage, and disease duration. Our results suggest that PD is related to widespread abnormal brain activities and that the abnormalities of ALFF in PD are associated with specific frequency bands. Future studies should take frequency band effects into account when examining spontaneous neural activity in PD.

14.
Neural Plast ; 2020: 8874119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354205

RESUMO

Background: Freezing of gait (FoG) is a disabling gait disorder that commonly occurs in advanced stages of Parkinson's disease (PD). The neuroanatomical mechanisms underlying FoG in PD are still unclear. The present study aims to explore alterations of structural gray matter (GM) in PD patients with FoG. Method: Twenty-four PD patients with FoG (FoG+), 37 PD patients without FoG (FoG-) and 24 healthy controls (HC) were included. All subjects underwent a standardized MRI protocol. The cortical thickness (CTh), segmentation volume without ventricles (BrainSegVolNotVent) and estimated total intracranial volume (eTIV) were analysed using the FreeSurfer pipeline. Results: CTh differences were found in the right middle temporal gyrus (rMTG) generally. Compared to that in HCs, the CTh of the rMTG in both the FoG+ and FoG- groups was smaller, while no significant difference between the FoG+ and FoG- groups. Correlation analyses demonstrated a negative correlation between the CTh of the rMTG and the UPDRS part II score in PD subjects, and a borderline significant correlation between the score of Freezing of Gait Questionnaire (FoGQ) and rMTG CTh. Additionally, receiver operating characteristic curve (ROC) analysis revealed a cut-off point of CTh =3.08 mm in the rMTG that could be used to differentiate PD patients and HCs (AUC =0.79, P <0.01). There were no differences in the BrainSegVolNotVent or eTIV among the 3 groups. Conclusions: Our findings currently suggest no significant difference between FoG+ and FoG- patients in terms of structural gray matter changes. However, decreased CTh in the rMTG related to semantic control may be used as a biomarker to differentiate PD patients and HCs.


Assuntos
Espessura Cortical do Cérebro , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Idoso , Feminino , Marcha/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
15.
Anal Cell Pathol (Amst) ; 2020: 2872479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381388

RESUMO

Background: Esophageal squamous cell carcinoma was treated by operation and chemoradiotherapy. However, the prognosis of most patients is poor after treatment, and most studies have shown that FGF2 and its receptor (FGFR) are involved in the development of various malignant tumors. FGF2 plays an important role in tumor progression and malignancy. In this study, the immunohistochemistry of FGF2, FGFR3, and FGFBP1 was used to further verify the expression of the three proteins in 172 patients with esophageal squamous cell carcinoma (ESCC) who had not received preoperative chemoradiotherapy and its effect on the prognosis of ESCC. Methods: (1) χ 2 test was used to analyze the relationship between proteins and clinicopathological parameters. Survival analysis was used to investigate the effect of three proteins on prognosis. (2) Paired sample t-test was used to analyze the mRNA expression of the three proteins in fresh ESCC tissues and adjacent normal tissues. Results: FGF2 was correlated with tumor size (p = 0.026), gender (p = 0.047), and lymph metastasis (p = 0.007) in ESCC tissues. The high expression of FGFR3 was associated with tumor differentiation (p = 0.043 and p < 0.05), lymph node metastasis (p = 0.078 and p < 0.1), and race (p = 0.033 and p < 0.05). The high expression of FGFBP1 was significantly associated with the degree of tumor differentiation (p = 0.012), age (p = 0.045), and lymph node metastasis (p = 0.032) of ESCC patients. The expression of FGF2, FGFR3, and FGFBP1-mRNA in ESCC tissues was significantly higher than that in adjacent tissues (p < 0.001, p < 0.001, and p = 0.001). Patients with high expression of FGF2, FGFBP1, and FGFR3 had poor prognosis. There was a weak positive correlation between FGF2 and FGFBP1, as well as FGFR. Conclusion: The FGF2-FGFR3 axis may promote the progression of esophageal squamous cell carcinoma. The FGF2-FGFR3 axis may be a new direction of targeted therapy for esophageal squamous cell carcinoma. FGF2 and FGFR3 may be used as prognostic markers of esophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Fator 2 de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Intervalo Livre de Progressão , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo
16.
Front Aging Neurosci ; 12: 580564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192473

RESUMO

Objective: This study aimed to explore alterations in the topological properties of the functional brain network in primary Parkinson's disease (PD) patients with freezing of gait (PD-FOG). Methods: Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 23 PD-FOG patients, 33 PD patients without FOG (PD-nFOG), and 24 healthy control (HC) participants. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and topological properties were analyzed by using graph theory approaches. The network-based statistics (NBS) method was used to determine the suprathreshold connected edges (P < 0.05; threshold T = 2.725), and statistical significance was estimated by using the non-parametric permutation method (5,000 permutations). Statistically significant topological properties were further evaluated for their relationship with clinical neurological scales. Results: The topological properties of the functional brain network in PD-FOG and PD-nFOG showed no abnormalities at the global level. However, compared with HCs, PD-FOG patients showed decreased nodal local efficiency in several brain regions, including the bilateral striatum, frontoparietal areas, visual cortex, and bilateral superior temporal gyrus, increased nodal local efficiency in the left gyrus rectus. When compared with PD-nFOG patients and HCs, PD-FOG showed increased betweenness centrality in the left hippocampus. Moreover, compared to HCs, both PD-FOG and PD-nFOG patients displayed reduced network connections by using the NBS method, mainly involving the sensorimotor cortex (SM), visual network (VN), default mode network (DMN), auditory network (AN), dorsal attention network (DAN), subcortical regions, and limbic network (LIM). The local node efficiency of the right temporal pole: superior temporal gyrus in PD-FOG patients was positively correlated with the Freezing of Gait Questionnaire (FOGQ) scores. Conclusions: This study demonstrates the disrupted regional topological organization in PD-FOG patients, especially associated with damage to the subcortical regions and multiple cortical regions. Our results provide insights into the dysfunctional mechanisms of the relevant networks and indicate potential neuroimaging biomarkers of PD-FOG.

17.
Neural Plast ; 2020: 8891458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101404

RESUMO

Background: Freezing of gait (FOG) is a disabling gait disorder influencing patients with Parkinson's disease (PD). Accumulating evidence suggests that FOG is related to the functional alterations within brain networks. We investigated the changes in brain resting-state functional connectivity (FC) in patients with PD with FOG (FOG+) and without FOG (FOG-). Methods: Resting-state functional magnetic resonance imaging (RS-fMRI) data were collected from 55 PD patients (25 FOG+ and 30 FOG-) and 26 matched healthy controls (HC). Differences in intranetwork connectivity between FOG+, FOG-, and HC individuals were explored using independent component analysis (ICA). Results: Seven resting-state networks (RSNs) with abnormalities, including motor, executive, and cognitive-related networks, were found in PD patients compared to HC. Compared to FOG- patients, FOG+ patients had increased FC in advanced cognitive and attention-related networks. In addition, the FC values of the auditory network and default mode network were positively correlated with the Gait and Falls Questionnaire (GFQ) and Freezing of Gait Questionnaire (FOGQ) scores in FOG+ patients. Conclusions: Our findings suggest that the neural basis of PD is associated with impairments of multiple functional networks. Notably, alterations of advanced cognitive and attention-related networks rather than motor networks may be related to the mechanism of FOG.

18.
Brief Bioinform ; 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079984

RESUMO

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

19.
Appl Environ Microbiol ; 86(17)2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32591384

RESUMO

Cometabolic degradation plays a prominent role in bioremediation of commingled groundwater contamination (e.g., chlorinated solvents and the solvent stabilizer 1,4-dioxane [dioxane]). In this study, we untangled the diversity and catalytic functions of multicomponent monooxygenases in Azoarcus sp. strain DD4, a Gram-negative propanotroph that is effective in degrading dioxane and 1,1-dichloroethylene (1,1-DCE). Using a combination of knockout mutagenesis and heterologous expression, a toluene monooxygenase (MO) encoded by the tmoABCDEF gene cluster was unequivocally proved to be the key enzyme responsible for the cometabolism of both dioxane and 1,1-DCE. Interestingly, in addition to utilizing toluene as a primary substrate, this toluene MO can also oxidize propane into 1-propanol. Expression of this toluene MO in DD4 appears inducible by both substrates (toluene and propane) and their primary hydroxylation products (m-cresol, p-cresol, and 1-propanol). These findings coherently explain why DD4 can grow on propane and express toluene MO for active cooxidation of dioxane and 1,1-DCE. Furthermore, upregulation of tmo transcription by 1-propanol underlines the implication potential of using 1-propanol as an alternative auxiliary substrate for DD4 bioaugmentation. The discovery of this toluene MO in DD4 and its degradation and induction versatility can lead to broad applications, spanning from environmental remediation and water treatment to biocatalysis in green chemistry.IMPORTANCE Toluene MOs have been well recognized given their robust abilities to degrade a variety of environmental pollutants. Built upon previous research efforts, this study ascertained the untapped capability of a toluene MO in DD4 for effective cooxidation of dioxane and 1,1-DCE, two of the most prevailing yet challenging groundwater contaminants. This report also aligns the induction of a toluene MO with nontoxic and commercially accessible chemicals (e.g., propane and 1-propanol), extending its implications in the field of environmental microbiology and beyond.


Assuntos
Azoarcus/enzimologia , Proteínas de Bactérias/metabolismo , Dicloroetilenos/metabolismo , Dioxanos/metabolismo , Oxigenases de Função Mista/metabolismo , Oxirredução
20.
Front Aging Neurosci ; 12: 53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210787

RESUMO

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively. Conclusion: Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD.

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