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1.
Int J Biol Macromol ; 249: 126016, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37516224

RESUMO

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.


Assuntos
Quitosana , Fragaria , Óleos Voláteis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Fragaria/microbiologia , Quitosana/química , Pectinas/farmacologia , Pectinas/química , Antioxidantes/farmacologia , Antioxidantes/química , Conservação de Alimentos/métodos
2.
Biofabrication ; 15(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37348491

RESUMO

Three-dimensional (3D)in vitrotumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5%-3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0%-2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. Reverse transcription-polymerase chain reaction (RT-qPCR) and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.


Assuntos
Bioimpressão , Neoplasias , Humanos , Alicerces Teciduais/química , Bioimpressão/métodos , Engenharia Tecidual/métodos , Gelatina/química , Impressão Tridimensional , Hidrogéis/farmacologia , Hidrogéis/química , Fatores Biológicos , Microambiente Tumoral
3.
J Alzheimers Dis ; 93(3): 977-990, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37212101

RESUMO

BACKGROUND: The association between poor oral health and the risk of incident dementia remains unclear. OBJECTIVE: To investigate the associations of poor oral health with incident dementia, cognitive decline, and brain structure in a large population-based cohort study. METHODS: A total of 425,183 participants free of dementia at baseline were included from the UK Biobank study. The associations between oral health problems (mouth ulcers, painful gums, bleeding gums, loose teeth, toothaches, and dentures) and incident dementia were examined using Cox proportional hazards models. Mixed linear models were used to investigate whether oral health problems were associated with prospective cognitive decline. We examined the associations between oral health problems and regional cortical surface area using linear regression models. We further explored the potential mediating effects underlying the relationships between oral health problems and dementia. RESULTS: Painful gums (HR = 1.47, 95% CI [1.317-1.647], p < 0.001), toothaches (HR = 1.38, 95% CI [1.244-1.538], p < 0.001), and dentures (HR = 1.28, 95% CI [1.223-1.349], p < 0.001) were associated with increased risk of incident dementia. Dentures were associated with a faster decline in cognitive functions, including longer reaction time, worse numeric memory, and worse prospective memory. Participants with dentures had smaller surface areas of the inferior temporal cortex, inferior parietal cortex, and middle temporal cortex. Brain structural changes, smoking, alcohol drinking, and diabetes may mediate the associations between oral health problems and incident dementia. CONCLUSION: Poor oral health is associated with a higher risk of incident dementia. Dentures may predict accelerated cognitive decline and are associated with regional cortical surface area changes. Improvement of oral health care could be beneficial for the prevention of dementia.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Demência/epidemiologia , Saúde Bucal , Estudos de Coortes , Estudos Prospectivos , Odontalgia , Disfunção Cognitiva/epidemiologia , Fatores de Risco
4.
Geroscience ; 45(3): 1997-2009, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37046127

RESUMO

Cohort studies report inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFA) or fish oil and dementia risk. Furthermore, evidence relating omega-6 polyunsaturated fatty acids (n-6 PUFA) with dementia is scarce. Here, we included 440,750 dementia-free participants from UK Biobank to comprehensively investigate the associations between plasma levels of different types of PUFA, fish oil supplementation, and dementia risk. During a median follow-up of 9.25 years, 7768 incident dementia events occurred. Higher plasma levels of five PUFA measures showed consistent associations with lower dementia risk (hazard ratios [95% confidence intervals] for per standard deviation increment of plasma concentrations 0.85 [0.81-0.89] for total PUFAs; 0.90 [0.86-0.95] for omega-3 PUFAs; 0.92 [0.87-0.96] for docosahexaenoic acid (DHA); 0.86 [0.82-0.90] for omega-6 PUFAs; 0.86 [0.82-0.90] for linoleic acid (LA); all p < 0.001). Compared with non-users, fish oil supplement users had a 7% decreased risk of developing all-cause dementia (0.93 [0.89-0.97], p = 0.002), and the relationship was partially mediated by plasma n-3 PUFA levels (omega-3 PUFAs: proportion of mediation = 57.99%; DHA: proportion of mediation = 56.95%). Furthermore, we observed significant associations of plasma n-3 PUFA levels and fish oil supplementation with peripheral immune markers that were related to dementia risk, as well as the positive associations of plasma PUFA levels with brain gray matter volumes and white matter microstructural integrity, suggesting they may affect dementia risk by affecting peripheral immunity and brain structure. Taken together, higher plasma PUFA levels and fish oil supplementation were associated with lower risk of incident dementia. This study may support the value of interventions to target PUFAs (specifically n-3 PUFAs) to prevent dementia.


Assuntos
Ácidos Graxos Ômega-3 , Óleos de Peixe , Humanos , Óleos de Peixe/química , Estudos Prospectivos , Ácidos Graxos Insaturados , Ácidos Docosa-Hexaenoicos , Estudos de Coortes , Suplementos Nutricionais
5.
Eur J Med Res ; 28(1): 155, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085944

RESUMO

BACKGROUND: Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS: New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS: Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.


Assuntos
Sepse , Fator A de Crescimento do Endotélio Vascular , Humanos , Hemoglobinas/metabolismo , Estudos Prospectivos , Reperfusão , Sepse/metabolismo , Sepse/patologia , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Phytomedicine ; 110: 154649, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36634379

RESUMO

BACKGROUND: Parkinson's disease (PD), the most common neurodegenerative disorder, primarily affects dopaminergic neurons in the substantia nigra (SN). In addition to severe motor dysfunction, PD patients appear apparent cognitive impairments in the late stage. Cognitive dysfunction is accompanied by synaptic transmission damage in the hippocampus. Cordycepin has been reported to alleviate cognitive impairments in neurodegenerative diseases. PURPOSE: The study aimed to estimate the protection roles of cordycepin on cognitive dysfunction in PD model and explore the potential mechanisms. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the PD model in vivo and in vitro experiments. In the in vivo experiments, the C57BL / 6 mice were intraperitoneally injected with MPTP and intragastric administration with cordycepin. Open field test (OFT) was used to estimate the exercise ability. Spontaneous alternation behavioral (SAB) and morris water maze (MWM) tests were used to evaluate the learning and memory abilities. The hippocampal slices from C57BL / 6 and Kunming mice in the in vitro experiments were used to record field excitatory postsynaptic potential (fEPSP) by electrophysiological methods. Western blotting was used to examine the level of tyrosine hydroxylase (TH) in the in vivo experiments and the levels of adenosine A1 and A2A receptors (A1R and A2AR) in the in vitro experiments, respectively. The drugs of MPTP, cordycepin, DPCPX and SCH58261 were perfused through dissolving in artificial cerebrospinal fluid. RESULTS: Cordycepin could significantly reduce the impairments on motor, exploration, spatial learning and memory induce by MPTP. MPTP reduced the amplitude of LTP in hippocampal CA1 area but cordycepin could improve LTP amplitudes. Cordycepin at dosage of 20 mg/kg also increased the TH level in SN. In the in vitro experiments, MPTP inhibited synaptic transmission in hippocampal Schaffer-CA1 pathway with a dose-dependent relationship, while cordycepin could reverse the inhibition of synaptic transmission. Furthermore, the roles of cordycepin on synaptic transmission could been attenuated in the presence of the antagonists of A1R and A2AR, DPCPX and SCH58261, respectively. Interestingly, the level of A2AR rather than A1R in hippocampus was significantly decreased in the cordycepin group as compared to the control. CONCLUSION: The present study has showed that cordycepin could improve cognitive function in the PD model induced by MPTP through regulating the adenosine A2A receptors. These findings were helpful to provide a new strategy for the dementia caused by Parkinson's disease.


Assuntos
Doença de Parkinson , Animais , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Adenosina , Cognição , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Doença de Parkinson/tratamento farmacológico
7.
Transl Psychiatry ; 12(1): 509, 2022 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496374

RESUMO

Based on risk profiles, several approaches for predicting dementia risk have been developed. Predicting the risk of dementia with accuracy is a significant clinical challenge. The goal was to create a modified dementia risk score (MDRS) based on a big sample size. A total of 239,745 participants from UK Biobank were studied (mean follow-up of 8.7 years). The score value of each risk factor was estimated according to the ß coefficient in the logistic regression model. The total dementia risk score was the sum of each risk score. Kaplan Meier survival curves and Cox proportional hazards analyses were used to assess the associations between total score and dementia. Among all participants included, 3531 incident cases of all-cause dementia (ACD), 1729 cases of Alzheimer's disease (AD), and 925 cases of vascular dementia (VD) were identified. Several vascular risk factors (physical activity, current smoking status, and glycemic status) and depressive symptoms were found to be significantly related to dementia risk. The modified dementia risk scores predicted dementia well (model 1, area under curve 0.810; model 2, area under curve 0.832). In model 1, the cut-off value for high risk (HR) was 81 or higher, and in model 2 (including the APOE4), it was 98 or higher. According to Kaplan-Meier survival analyses, patients in the HR group had faster clinical progression (p < 0.0001) in either model 1 or 2. Cox regression analyses for HR versus low risk (LR) revealed that the Hazard radio for ACD was 7.541 (6.941 to 8.193) in model 1 and 8.348 (7.727 to 9.019) in model 2. MDRS is appropriate for dementia primary prevention, and may help quickly identify individuals with elevated risk of dementia.


Assuntos
Doença de Alzheimer , Demência , Humanos , Demência/diagnóstico , Demência/epidemiologia , Demência/etiologia , Estudos Prospectivos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/complicações , Fatores de Risco , Estimativa de Kaplan-Meier
8.
J Alzheimers Dis ; 90(3): 1249-1261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245378

RESUMO

BACKGROUND: Previous studies have reported inconsistent associations between chronic kidney disease (CKD) and dementia. OBJECTIVE: To evaluate whether CKD is a risk factor for dementia and compare the performance of different measures of calculating estimated glomerular filtration rate (eGFR). METHODS: 275,167 participants from UK Biobank were included and eGFR at baseline was calculated using serum creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C equations (eGFRcr-cys). Restricted cubic splines and Cox regression models were performed to assess the relationship of eGFR with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: We observed a U-shaped relationship between each eGFR and risk of all-cause dementia and VaD, with eGFRcys and eGFRcr-cys showing a closer linkage (peGFRcys <0.0001, peGFRcrhboxcys<0.0001 and peGFRcr = 0.0001). Lower and supranormal eGFR were related to increased risk of all-cause dementia. Compared to the reference category of 90-104 ml/min/1.73 m2, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause dementia for eGFRcr-cys 30-59, <30, and ≥105 ml/min/1.73 m2 were 1.26 (95% CI [1.05-1.50], p = 0.012), 2.62 (95% CI [1.54-4.47], p < 0.001), and 1.41 (95% CI [1.17-1.70], p < 0.001). No statistically significant association was observed between eGFR with risk of AD. CONCLUSION: This prospective study identified impaired kidney function as a critical risk factor for dementia and noted the application of cystatin C strengthened the relationship between CKD and dementia, underlining the significant value of preserving kidney function to reduce the risk of dementia and considering cystatin C measurement as part of clinical practice.


Assuntos
Demência , Insuficiência Renal Crônica , Humanos , Cistatina C , Estudos Prospectivos , Bancos de Espécimes Biológicos , Taxa de Filtração Glomerular , Creatinina , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Rim , Demência/epidemiologia , Reino Unido/epidemiologia
9.
Quant Imaging Med Surg ; 12(10): 4953-4967, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36185059

RESUMO

Background: Tissue oedema affects tissue perfusion and interferes with the monitoring of tissue oxygenation in patients with severe sepsis. However, the underlying mechanisms remain unclear. We used a wireless near-infrared spectroscopy (NIRS) device that transmits tri-wavelength light to quantify tissue haemoglobin (Hb) and water (H2O) content. We estimated tissue H2O in severe sepsis patients and healthy controls, compared their difference, and investigated the correlation of tissue H2O with systemic haemodynamics and its impact on tissue oxygenation. Methods: Seventy-seven adult patients with new-onset severe sepsis admitted to the intensive care unit within 72 h and 30 healthy volunteers (controls) were enrolled. The NIRS device was placed on the participant's leg to estimate the relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) at rest for three consecutive days. Two-sample t-test or Mann-Whitney U test, chi-square test, and generalised estimating equations (GEEs) were used for comparisons. Results: In severe sepsis patients, the [H2O] in the anterior tibia was higher [mean (standard deviation, 95% confidence interval), 10.57 (3.37, 9.81-11.34) vs. 7.40 (1.89, 6.70-8.11)] and the [HbO2], [HbT], and tissue Hb oxygen saturation (StO2) were lower [0.20 (0.01, 0.20-0.20) vs. 0.22 (0.01, 0.22-0.23), 0.42 (0.02, 0.42-0.43) vs. 0.44 (0.02, 0.44-0.45), and 47.25% (1.97%, 46.80-47.70%) vs. 49.88% (1.26%, 49.41-50.35%), respectively] than in healthy controls in first-day measurements. GEE analysis revealed significant differences in [H2O], [HbO2], [HbT], and StO2 between groups over three consecutive days (all P≤0.001). In addition, [HbO2] and StO2 levels gradually decreased over time in the patient group. A negative correlation was observed between [H2O] and [HbO2] and StO2, which became more obvious over time (day 1: r=-0.51 and r=-0.42, respectively; both P<0.01; day 3: r=-0.67 and r=-0.63, respectively, both P<0.01). Systolic arterial pressure was positively related to [H2O] (r=0.51, P<0.05, on day 1) but was not associated with tissue oxygenation parameters. Conclusions: NIRS can be used to quantify tissue H2O. Severe sepsis patients have increased tissue H2O, which responds to changes in arterial blood pressure and affects tissue oxygenation.

10.
Front Cell Dev Biol ; 10: 891332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832792

RESUMO

With great sadness, the scientific community received the news of the loss of Beth Levine on 15 June 2020. Dr. Levine was a pioneer in the autophagy field and work in her lab led not only to a better understanding of the molecular mechanisms regulating the pathway, but also its implications in multiple physiological and pathological conditions, including its role in development, host defense, tumorigenesis, aging or metabolism. This review does not aim to provide a comprehensive view of autophagy, but rather an outline of some of the discoveries made by the group of Beth Levine, from the perspective of some of her own mentees, hoping to honor her legacy in science.

11.
J Agric Food Chem ; 70(25): 7773-7785, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35713646

RESUMO

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside (THSG), a polyphenol stilbene compound, is the main active constituent in Polygonum multiflorum. In this study, a comprehensive analytical strategy was developed for the characterization of THSG metabolites in vivo (rat plasma, bile, urine, heart, liver, spleen, lung, kidney, and stomach) utilizing ultrahigh performance liquid chromatography coupled with Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q Exactive-Orbitrap MS) based on multiple data-processing techniques. As a result, a total of 75 metabolites were characterized in bio-samples, and calculated Clog P values were further employed to assign the chemical structures of some isomers. Glucoside hydrolysis, hydrogenation, hydroxylation, glucuronide conjugation, and sulfate conjugation would be the major metabolic pathways of THSG. It appeared that most metabolites would generally undergo phase I reactions followed by phase II reactions. These results provided valuable information for in-depth understanding of the safety and efficacy of THSG and showed a valuable methodology for metabolic characterization.


Assuntos
Estilbenos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Glucosídeos , Ratos
12.
ACS Appl Mater Interfaces ; 14(22): 25183-25196, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35638599

RESUMO

Chemodynamic therapy (CDT), as a powerful tumor therapeutic approach with low side effects and selective therapeutic efficiency, has gained much attention. However, the low intracellular content of H2O2 and the cellular bottleneck of low intracellular oxidative reaction rates at tumor sites have limited the antitumor efficacy of CDT. Herein, a series of sulfur-deficient engineered biodegradable cobalt sulfide quantum dots (CoSx QDs) were constructed for improved synergistic photothermal- and hyperthermal-enhanced CDT of tumors through regulating the photothermal conversion efficiency (PCE) and Fenton-like activity. Through defect engineering, we modulated the PCE and promoted the Fenton catalytic capability of CoSx QDs. With increasing defect sites, the Fenton-like activity improved to generate more toxic •OH, while the photothermal effect declined slightly. In light of above unique superiorities, the best synergistic effects of CoSx QDs were obtained through comparing their PCE and catalytic activity by regulating the sulfur defect fraction degree in these QDs during the synthetic process. In addition, the ultrasmall size and biodegradation endowed QDs with the ability to be rapidly decomposed to ions that were easily excreted after therapy, thus reducing biogenic accumulation in the body with lowered systemic side effects. The in vitro/vivo results demonstrated that the photothermal- and hyperthermal-enhanced chemodynamic effect of CoSx QDs can enable remarkable anticancer properties with favorable biocompatibility. In this study, the defect-driven mechanism for the photothermal-enhanced Fenton-like reaction provides a flexible strategy to deal with different treatment environments, holding great promise in developing a multifunctional platform for cancer treatment in the future.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Linhagem Celular Tumoral , Cobalto , Humanos , Peróxido de Hidrogênio/metabolismo , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Enxofre
13.
Healthcare (Basel) ; 10(5)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35628039

RESUMO

Respiratory arousal is the change from a state of sleep to a state of wakefulness following an apnea or hypopnea. In patients with obstructive sleep apnea (OSA), it could have a helpful role to activate upper airway muscles and the resumption of airflow and an opposing role to contribute to greater ventilatory instability, continue cycling, and likely exacerbate OSA. Patients with very severe OSA (apnea-hypopnea index (AHI) ≥ 60 events/h) may have specific chemical (e.g., possible awake hypercapnic hypoxemia) and mechanical (e.g., restricted dilator muscles) stimuli to initiate a respiratory arousal. Little was reported about how respiratory arousal presents in this distinct subgroup, how it relates to AHI, Epworth Sleepiness Scale (ESS), body mass index (BMI), and oxygen saturation, and how a non-framework surgery may change it. Here, in 27 patients with very severe OSA, we show respiratory arousal index was correlated with each of AHI, mean oxyhemoglobin saturation of pulse oximetry (SpO2), mean desaturation, and desaturation index, but not in BMI or ESS. The mean (53.5 events/h) was higher than other reports with less severe OSAs in the literature. The respiratory arousal index can be reduced by about half (45.3%) after a non-framework multilevel surgery in these patients.

14.
Sci Rep ; 12(1): 2251, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145170

RESUMO

A non-framework surgery could change the postoperative components of breathing disturbances and increase the frequency or duration of hypopnea in patients with very severe obstructive sleep apnea (OSA). Either an increase of hypopnea index, which increases apnea-hypopnea index (AHI), or an increase of its duration raises the concern of worsening the oxygen desaturation and so morbidity and mortality associated with OSA. It is unclear how the oxygen saturation would change in those having increased frequency or duration of hypopneas after the surgery. Here in 17 patients with AHI ≥ 60 events/h, having increased frequency or duration of hypopneas after the non-framework surgery, the results show that the surgery improved oxygen saturation by reducing obstructive-apnea index (36.1 events/h) and duration (8.6 s/event), despite it increased hypopnea index (16.8 events/h) and duration (9.8 s/event). The surgery improved the average of the mean oxyhemoglobin saturation of pulse oximetry (SpO2) by 2.8% (toward a ceiling mean of 94.3%), mean minimal SpO2 by 7.5%, and mean desaturation by 5%. The results suggest sufficient apnea reduction and shift from apnea to hypopnea may mask the negative impact of the increase of hypopnea index or duration and improve postoperative mean SpO2, minimal SpO2, and mean desaturation.


Assuntos
Glossectomia/estatística & dados numéricos , Saturação de Oxigênio , Palato/cirurgia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Biomed Res Int ; 2021: 7408497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631887

RESUMO

In patients of oral cavity or oropharyngeal cancers, resection of the tumor and reconstruction of the defect may reduce the framework, add a bulky flap, alter the tissue flexibility, and contribute to postoperative obstructive sleep apnea (OSA). Postoperative OSA and the potential consequences may decrease the survival rate and reduce patients' quality of life. It is unclear whether the surgery is associated with postoperative OSA. Here, we compared the polysomnographies (PSGs) before and after the surgery in 15 patients of oral cavity or oropharyngeal cancers (out of 68 patients of head and neck cancers) without a chemo- or radio-therapy. Each patient received the second PSG before the start of any indicated adjuvant therapy to prevent its interference. There were 14 men and 1 woman, with a mean age and a standard deviation (SD, same in the following) of 56.2 ± 12.8 years. There were 6 tongue cancers, 5 buccal cancers, 2 tonsil cancer, 1 lower gum cancer, and 1 trigone cancer. The results show that the surgery changed sleep parameters insignificantly in apnea-hypopnea index (AHI), mean oxyhemoglobin saturation of pulse oximetry (SpO2), minimum SpO2, mean desaturation, and desaturation index but increased mean heart rate in the patients with free flaps. These results hint that the effect of surgery on developing OSA was small in this sample, with a longer plate or a larger framework for a bulkier free flap. It needs future studies with a large sample size to generalize this first observation.


Assuntos
Neoplasias Bucais/fisiopatologia , Neoplasias Bucais/cirurgia , Neoplasias Orofaríngeas/fisiopatologia , Neoplasias Orofaríngeas/cirurgia , Sono/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Saturação de Oxigênio , Oxiemoglobinas
16.
Anal Chem ; 93(42): 14106-14112, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34657416

RESUMO

Dengue fever is caused by mosquito-transmitted dengue virus infection and continues to increase worldwide, threatening public health in tropical and subtropical regions. The primary difficulties in preventing a reduction of the medical burden of dengue fever lies in the lack of effective mosquito control, preventive dengue vaccines, and clinically effective antiviral drugs to treat dengue infections. Rapid and accurate diagnosis is crucial for proper patient care and effective control of epidemics. The present work proposes an alternative strategy for detecting the dengue virus nonstructural protein 1 (NS1) antigen in clinical serum samples by using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in combination with the molecularly imprinted polymers. Rather than the whole protein, the NS1 signature peptide is selected as a template for molecular imprinting and quantified as a stoichiometric readout of NS1. Three functional monomers with hydrophobic, positively charged, and negatively charged groups were synthesized by click reactions in terms of the signature peptide. These three functional monomers provide abundant recognition sites for the peptide, allowing the peptide template to be effectively imprinted during polymerization. The imprinting conditions were optimized, and the molecularly imprinted polymers were characterized and used for enriching the signature peptide from digested serum samples by solid-phase extraction and then detected by UHPLC-MS/MS. The proposed method is used to detect the dengue virus NS1 in clinical samples and holds significant promise for early confirmation of dengue virus infection.


Assuntos
Vírus da Dengue , Dengue , Impressão Molecular , Cromatografia Líquida de Alta Pressão , Dengue/diagnóstico , Humanos , Peptídeos , Espectrometria de Massas em Tandem , Proteínas não Estruturais Virais
17.
Transl Neurosci ; 12(1): 351-361, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34703626

RESUMO

Formaldehyde (FA) is a commercially important chemical applied in industry and scientific research. However, FA has a distinct impact on learning and memory. Although the mechanisms of FA toxicity have been well studied, additional research is required to establish the mechanisms of neuroprotection in cases of FA exposure. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid with a variety of health benefits, including the enhancement of learning and memory. In this study, we investigated the neuroprotective effects of DHA in Drosophila melanogaster that had ingested FA. Our data suggested that DHA enhanced reproductive processes, leading to an increase in the number of eggs, larvae, and adults. Surprisingly, we found that DHA had a mild protective effect against FA-induced impairments in learning and memory.

18.
Alzheimers Res Ther ; 13(1): 158, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560893

RESUMO

BACKGROUND: Observational studies have suggested that herpesvirus infection increased the risk of Alzheimer's disease (AD), but it is unclear whether the association is causal. The aim of the present study is to evaluate the causal relationship between four herpesvirus infections and AD. METHODS: We performed a two-sample Mendelian randomization analysis to investigate association of four active herpesvirus infections with AD using summary statistics from genome-wide association studies. The four herpesvirus infections (i.e., chickenpox, shingles, cold sores, mononucleosis) are caused by varicella-zoster virus, herpes simplex virus type 1, and Epstein-Barr virus (EBV), respectively. A large summary statistics data from International Genomics of Alzheimer's Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was further performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD and 272,244 controls). RESULTS: We found evidence of a significant association between mononucleosis (caused by EBV) and risk of AD after false discovery rates (FDR) correction (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.092-2.446, P = 0.017, FDR-corrected P = 0.034). It has been verified in validation analysis that mononucleosis is also associated with family history of AD (OR [95% CI] = 1.392 [1.061, 1.826], P = 0.017). Genetically predicted shingles were associated with AD risk (OR [95% CI] = 0.867 [0.784, 0.958], P = 0.005, FDR-corrected P = 0.020), while genetically predicted chickenpox was suggestively associated with increased family history of AD (OR [95% CI] = 1.147 [1.007, 1.307], P = 0.039). CONCLUSIONS: Our findings provided evidence supporting a positive relationship between mononucleosis and AD, indicating a causal link between EBV infection and AD. Further elucidations of this association and underlying mechanisms are likely to identify feasible interventions to promote AD prevention.


Assuntos
Doença de Alzheimer , Infecções por Vírus Epstein-Barr , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/genética , Estudo de Associação Genômica Ampla , Herpesvirus Humano 4/genética , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
19.
Cell Rep ; 36(12): 109729, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34551295

RESUMO

Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibit age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, and are ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO is also rescued by neuronally expressing UQCRC1, but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associates with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increases cyt-c in the cytoplasmic fraction and activates the caspase cascade. Depleting cyt-c or expression of the anti-apoptotic p35 ameliorates uqcrc1-mediated neurodegeneration. Our findings identify a role for UQCRC1 in regulating cyt-c-induced apoptosis.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Proteínas de Drosophila/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Citocromos c/metabolismo , Citoplasma/metabolismo , Neurônios Dopaminérgicos/citologia , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/genética , Complexo III da Cadeia de Transporte de Elétrons/deficiência , Complexo III da Cadeia de Transporte de Elétrons/genética , Edição de Genes , Humanos , Larva/metabolismo , Locomoção , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Ligação Proteica , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo
20.
Cell Rep ; 35(2): 108972, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852856

RESUMO

Disruption of sphingolipid homeostasis is known to cause neurological disorders, but the mechanisms by which specific sphingolipid species modulate pathogenesis remain unclear. The last step of de novo sphingolipid synthesis is the conversion of dihydroceramide to ceramide by dihydroceramide desaturase (human DEGS1; Drosophila Ifc). Loss of ifc leads to dihydroceramide accumulation, oxidative stress, and photoreceptor degeneration, whereas human DEGS1 variants are associated with leukodystrophy and neuropathy. In this work, we demonstrate that DEGS1/ifc regulates Rac1 compartmentalization in neuronal cells and that dihydroceramide alters the association of active Rac1 with organelle-mimicking membranes. We further identify the Rac1-NADPH oxidase (NOX) complex as the major cause of reactive oxygen species (ROS) accumulation in ifc-knockout (ifc-KO) photoreceptors and in SH-SY5Y cells with the leukodystrophy-associated DEGS1H132R variant. Suppression of Rac1-NOX activity rescues degeneration of ifc-KO photoreceptors and ameliorates oxidative stress in DEGS1H132R-carrying cells. Therefore, we conclude that DEGS1/ifc deficiency causes dihydroceramide accumulation, resulting in Rac1 mislocalization and NOX-dependent neurodegeneration.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Ácidos Graxos Dessaturases/genética , Proteínas de Membrana/genética , NADPH Oxidases/genética , Proteínas rac1 de Ligação ao GTP/genética , Animais , Linhagem Celular Tumoral , Ceramidas/metabolismo , Proteínas de Drosophila/deficiência , Drosophila melanogaster/metabolismo , Eletrorretinografia , Ácidos Graxos Dessaturases/antagonistas & inibidores , Ácidos Graxos Dessaturases/metabolismo , Regulação da Expressão Gênica , Humanos , Proteínas de Membrana/deficiência , NADPH Oxidases/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo , Células Fotorreceptoras de Invertebrados/metabolismo , Células Fotorreceptoras de Invertebrados/patologia , Mutação Puntual , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Retina/metabolismo , Retina/patologia , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
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