Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
1.
J Genet Genomics ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530168

RESUMO

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, have greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy-number-variations (CNVs) called from 100-kb white blood cell DNA sequence windows by means of semi-supervised clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types respectively with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine-learning method enabled the classification of the CNVs obtained into the D group, V group, total-patient group and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be employed for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordnce between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominanly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.

2.
ACS Nano ; 15(9): 14509-14521, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34405679

RESUMO

Focused ultrasound (FUS) combined with microbubbles (MBs) has recently emerged as a potential approach to open the blood-brain barrier (BBB) for delivering drugs into the brain. However, appropriate approaches are still lacking to monitor the sublethal damage during FUS-mediated BBB opening in vivo, especially the early stage cell apoptotic events. Here, we developed a kind of nanoprobe-loaded MBs (AV-ICG-NPs@MBs) which can monitor the apoptotic cells that occur during FUS-mediated BBB opening through encapsulating the annexin V-targeted nanoprobes AV-ICG-NPs into the cavity of lipid-PLGA hybrid MBs. When irradiated by FUS, AV-ICG-NPs@MBs in the cerebral blood vessels would produce cavitation, favoring the BBB opening. Meanwhile, AV-ICG-NPs@MBs would be destroyed and release their AV-ICG-NPs payload. These released AV-ICG-NPs can be further delivered into the brain via the destructed BBB and bind with the phosphatidylserine externalized on the membrane of apoptotic cells if this occurs, leading to the prolonged detention of fluorescent signals in the brain. Furthermore, we also provided an effective strategy to inhibit or reverse the possible damage to the brain from a FUS-mediated BBB opening technology, through developing AV-ICG-NPs/GAS@MBs that encapsulate the antioxidant gastrodin (GAS) into AV-ICG-NPs@MBs. Accompanied by FUS irradiation and bubble cavitation, GAS was released and delivered into the brain, where they scavenged the oxygen free radicals produced from cavitation, leading to significantly lower fluorescence signals in the brain due to the absence of externalized phosphatidylserine. In conclusion, our study provides an approach to monitor and inhibit cell apoptotic events during FUS-mediated BBB opening.


Assuntos
Apoptose , Barreira Hematoencefálica
3.
Sci Total Environ ; 802: 149825, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34450438

RESUMO

Antidepressants have become ubiquitous emerging organic pollutants. Therefore, it is essential to investigate photodegradation of the antidepressants in environment waters for their ecological risk assessment. However, photodegradation behavior of antidepressants varied from different structures and photodegradation mechanism was rarely known for most antidepressants. Herein, citalopram (CIT), paroxetine (PAR) and fluvoxamine (FLUVO) were employed to study the photodegradation behavior of antidepressants in lake water. Results show that direct photolysis of CIT decreased when pH increased from 6 to 9 while the pH effect was not obvious on direct photolysis of FLUVO and PAR. Photodegradation of CIT occurred from its triplet-state and can undergo self-photosensitization through reaction with the generated hydroxyl radical (·OH). In lake water, PAR and FLUVO are degraded mainly via direct photolysis, while CIT is transformed mainly via indirect photolysis. Dissolved organic matter (DOM) and NO3- was proved to be the main factors affecting antidepressants photodegradation in lake water. DOM and NO3- showed inhibition effect on photodegradation of FLUVO and PAR, while promoted CIT degradation. The promotion effect of CIT was mainly through reaction with ·OH and excited triplet-state of DOM while singlet oxygen played a minor role. Based on the photodegradation products identified by MS/MS, the photodegradation pathways were proposed for CIT and PAR, respectively. For FLUVO, one (Z)-isomer degradation product was also found. Understanding the photodegradation behavior of antidepressants is vital for providing data to do ecological risk assessment.

4.
Aging (Albany NY) ; 13(15): 19529-19541, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349039

RESUMO

AIMS: Premenstrual dysphoric disorder (PMDD) is a psychiatric condition that is associated with the menstrual cycle. Elucidation of the neural regulation mechanisms of brain reactivity to emotional stimuli among women with PMDD may inform PMDD treatment. METHODS: Eighty-six women (42 PMDD, 44 healthy controls) were allocated into two groups (anger-induced group: 23 PMDD vs. 23 controls; depression-induced group: 19 PMDD vs. 21 controls). During the luteal phases of the menstrual cycle, all the women were subjected to functional magnetic resonance imaging (fMRI). fMRI resting-state scans were performed before and after the study participants had performed an emotional stimuli task. After the emotional stimuli task, emotional status of the participants were evaluated by Self-Rating Depression Scales (SDS) and Trait Anger Expression Inventory-II (STAXI-II). In addition, all the participants were requested to complete the Eysenck Personality Questionnaire (EPQ) and the Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: Compared to healthy controls, all women with PMDD exhibited significantly high scores in Tas-20 (p<0.001), higher neuroticism and psychoticism scores as well as significantly low extraversion and social desirability scores (p<0.05). Compared to the controls, f-MRI revealed that PMDD women had elevated ReHo in the middle frontal gyrus (BA10), temporal lobe (BA42), left cerebellum (BA37), as well as decreased activation in the precuneus (BA7), superior frontal gyrus (BA8), lobulus paracentralis (BA6), and right cerebellum (BA48) (p<0.05). Moreover, depression stimuli showed that women with PMDD had elevated ReHo levels in the middle frontal gyrus (BA11), the middle gyrus (BA47) and in the cingulate gyrus (BA23) vs. healthy controls (p<0.05). CONCLUSIONS: Women with more neuroticism and psychoticism, less extraversion and social desirability tend to report PMDD symptoms. Women with this condition experience difficulties in regulating emotions during the luteal phase of the menstrual cycle. Abnormal ReHo levels in the precuneus, superior frontal gyrus, lobulus paracentralis, and right cerebellum may contribute to anger dysregulation. Hypoactivation in the middle frontal gyrus, the middle gyrus and the cingulate gyrus may be generally associated with depression dysregulation in PMDD.

5.
Pharmaceutics ; 13(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34452234

RESUMO

Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of the blood-brain barrier (BBB), which greatly limits the availability of therapeutic drugs to the tumor. Ultrasound-mediated BBB opening provides a promising approach to help deliver drugs to brain tumors. The use of temozolomide (TMZ) in the clinical treatment of GBM has been shown to be able to increase survival in patients with GBM, but this improvement is still trivial. In this study, we developed a liposomal temozolomide formulation (TMZ-lipo) and locally delivered these nanoparticles into GBM through ultrasound-mediated BBB opening technology, significantly suppressing tumor growth and prolonging tumor-bearing animal survival. No significant side effects were observed in comparison with control rats. Our study provides a novel strategy to improve the efficacy of TMZ against GBM.

6.
Molecules ; 26(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299529

RESUMO

Aroma deterioration is one of the biggest problems in processing tea beverages. The aroma of tea infusion deteriorates fast during heat sterilization and the presence of ferrous ion (Fe2+) aggravates it. The underlying mechanism remains unveiled. In this study, Fe2+ was verified to deteriorate the aroma quality of green tea infusion with heat treatment. Catechins were necessary for Fe2+-mediated aroma deterioration. By enhancing the degradation of catechins, Fe2+ dramatically increased the production of hydrogen peroxide (H2O2). Fe2+ and H2O2 together exacerbated the aroma of green tea infusion with heat treatment. GC-MS analysis revealed that the presence of Fe2+ enhanced the loss of green/grassy volatiles and promoted the formation of new volatiles with diversified aroma characteristics, resulting in a dull scent of green tea infusion. Our results revealed how Fe2+ induced aroma deterioration of green tea infusion with heat treatment and could help guide tea producers in attenuating the aroma deterioration of tea infusion during processing.


Assuntos
Compostos Ferrosos/análise , Odorantes/análise , Chá/química , Catequina/química , Cátions Bivalentes/análise , Temperatura Alta , Ferro/análise , Esterilização
7.
Proc Natl Acad Sci U S A ; 118(29)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34266953

RESUMO

p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPß, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.

8.
J Alzheimers Dis ; 82(3): 1123-1136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151789

RESUMO

BACKGROUND: Sensitive measures of cognition are needed in preclinical and prodromal Alzheimer's disease (AD) to track cognitive change and evaluate potential interventions. Neurofibrillary tangle pathology in AD is first observed in Brodmann Area 35 (BA35), the medial portion of the perirhinal cortex. The importance of the perirhinal cortex for semantic memory may explain early impairments of semantics in preclinical AD. Additionally, our research has tied figurative language impairment to neurodegenerative disease. OBJECTIVE: We aim to identify tasks that are sensitive to cognitive impairment in individuals with mild cognitive impairment (MCI), and that are sensitive to atrophy in BA35. METHODS: Individuals with MCI and cognitively normal participants (CN) were tested on productive and receptive experimental measures of semantic memory and experimental tests of figurative language comprehension (including metaphor and verbal analogy). Performance was related to structural imaging and standard neuropsychological assessment. RESULTS: On the experimental tests of semantics and figurative language, people with MCI performed worse than CN participants. The experimental semantic memory tasks are sensitive and specific; performance on the experimental semantic memory tasks related to medial temporal lobe structural integrity, including BA35, while standard neuropsychological assessments of semantic memory did not, demonstrating the sensitivity of these experimental measures. A visuo-spatial analogy task did not differentiate groups, confirming the specificity of semantic and figurative language tasks. CONCLUSION: These experimental measures appear sensitive to cognitive change and neurodegeneration early in the AD trajectory and may prove useful in tracking cognitive change in clinical trials aimed at early intervention.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Testes de Estado Mental e Demência/normas , Sintomas Prodrômicos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Reprodutibilidade dos Testes
9.
Food Chem ; 364: 130235, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175625

RESUMO

The effects of brewing water on the sensory attributes and physicochemical properties of tea infusions made from Chinese teas were investigated. The tea infusions brewed in water with higher pH and total dissolved solids (TDS), generally had a darker color and lower overall sensory acceptability. Moreover, those infusions had less catechins, particularly galloylated-catechins, and lower antioxidant capacity. The teas with less fermentation contained more galloylated-catechins and had higher antioxidant capacity, but were much more susceptible to high mineral brewing water. Green tea was proved to be the most susceptible one, whereas dark tea the most stable one. Green tea infusions prepared with higher pH/TDS water were more rapidly oxidized, resulting in a darker color due to polymerization of catechins, when exposed to the air. These findings suggested that low mineral brewing water was better for Chinese tea, both from the sensory and health benefit perspectives.


Assuntos
Camellia sinensis , Catequina , Antioxidantes/análise , Catequina/análise , Chá , Água
10.
Neuroimage Clin ; 31: 102717, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34119903

RESUMO

Mild cognitive impairment (MCI) can be an early manifestation of Alzheimer's disease (AD) pathology, other pathologic entities [e.g., cerebrovascular disease, Lewy body disease, LATE (limbic-predominant age-related TDP-43 encephalopathy)], or mixed pathologies, with concomitant AD- and non-AD pathology being particularly common, albeit difficult to identify, in living MCI patients. The National Institute on Aging and Alzheimer's Association (NIA-AA) A/T/(N) [ß-Amyloid/Tau/(Neurodegeneration)] AD research framework, which classifies research participants according to three binary biomarkers [ß-amyloid (A+/A-), tau (T+/T-), and neurodegeneration (N+/N-)], provides an indirect means of identifying such cases. Individuals with A+T-(N+) MCI are thought to have both AD pathologic change, given the presence of ß-amyloid, and non-AD pathophysiology, given neurodegeneration without tau, because in typical AD it is tau accumulation that is most tightly linked to neuronal injury and cognitive decline. Thus, in A+T-(N+) MCI (hereafter referred to as "mismatch MCI" for the tau-neurodegeneration mismatch), non-AD pathology is hypothesized to drive neurodegeneration and symptoms, because ß-amyloid, in the absence of tau, likely reflects a preclinical stage of AD. We compared a group of individuals with mismatch MCI to groups with A+T+(N+) MCI (or "prodromal AD") and A-T-(N+) MCI (or "neurodegeneration-only MCI") on cross-sectional and longitudinal cognition and neuroimaging characteristics. ß-amyloid and tau status were determined by CSF assays, while neurodegeneration status was based on hippocampal volume on MRI. Overall, mismatch MCI was less "AD-like" than prodromal AD and generally, with some exceptions, more closely resembled the neurodegeneration-only group. At baseline, mismatch MCI had less episodic memory loss compared to prodromal AD. Longitudinally, mismatch MCI declined more slowly than prodromal AD across all included cognitive domains, while mismatch MCI and neurodegeneration-only MCI declined at comparable rates. Prodromal AD had smaller baseline posterior hippocampal volume than mismatch MCI, and whole brain analyses demonstrated cortical thinning that was widespread in prodromal AD but largely restricted to the medial temporal lobes (MTLs) for the mismatch and neurodegeneration-only MCI groups. Longitudinally, mismatch MCI had slower rates of volume loss than prodromal AD throughout the MTLs. Differences in cross-sectional and longitudinal cognitive and neuroimaging measures between mismatch MCI and prodromal AD may reflect disparate underlying pathologic processes, with the mismatch group potentially being driven by non-AD pathologies on a background of largely preclinical AD. These findings suggest that ß-amyloid status alone in MCI may not reveal the underlying driver of symptoms with important implications for enrollment in clinical trials and prognosis.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Peptídeos beta-Amiloides , Biomarcadores , Estudos Transversais , Progressão da Doença , Humanos , Irmãos , Proteínas tau
11.
Cancer Res ; 81(15): 4041-4053, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34099490

RESUMO

Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which, R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy. SIGNIFICANCE: These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy.

12.
Theranostics ; 11(14): 7005-7017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093867

RESUMO

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Indóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Fenotiazinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Disponibilidade Biológica , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/química , Indóis/farmacocinética , Indóis/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Fenotiazinas/química , Fenotiazinas/farmacocinética , Fenotiazinas/uso terapêutico , Espectroscopia de Infravermelho com Transformada de Fourier , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Biomater Sci ; 9(11): 4127-4138, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33954320

RESUMO

Ultrasound-activated microbubble destruction is a promising platform for gene delivery due to the low toxicity, non-invasiveness, and high specificity. However, the gene transfection efficiency is still low, especially for suspension cells. It is desirable to develop a universal gene delivery tool that overcomes the drawbacks existing in ultrasound-mediated methods. Here, we present a three-dimensional acoustic field-based conformal transfection (AFCT) system by designing a Sono-hole that can fit the three-dimensional acoustic field to maximally utilize the acoustic energy from bubble cavitation, thus greatly promoting the gene delivery efficiency. Surprisingly, compared with the traditional two-dimensional transfection system, the gene transfection efficiency of the AFCT system increased by more than 3 times, achieving nearly 30%. The parameters including acoustic pressure, duration, duty cycle, DNA concentrations, and bubble kinds were optimized to obtain higher gene transfection. In conclusion, our study provides an effective ultrasound-based gene delivery approach for gene transfection, especially for suspension-cultured cells.


Assuntos
Microbolhas , Ultrassom , Acústica , Técnicas de Transferência de Genes , Transfecção
14.
Water Res ; 197: 117078, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33819659

RESUMO

The impact of HCO3- on the photodegradation of ß-blockers was investigated under simulated sunlight irradiation. The results show that in the presence of HCO3-, the photodegradation rates increase significantly for sotalol (SOT), whereas no effects on the degradation of carvedilol and arotinolol are observed. Using quenching experiments, electron paramagnetic resonance spectra and degradation product determination, we demonstrate that carbonate radical (CO3•-) is formed by direct oxidation of HCO3- by triplet-excited SOT (3SOT*) and plays a significant role in SOT photodegradation. Competition kinetics experiments show that the three ß-blockers all have high second-order rate constants (107-108 M-1 s-1) for the reaction with CO3•-. However, only 3SOT* has a higher reduction potential that can oxidize HCO3- to produce CO3•-. Thus, enhanced SOT removal rates in the presence of HCO3- were observed. In addition, the results show that seawater DOM could increase HCO3--induced photodegradation of SOT, whereas SRNOM mainly behaves as a CO3•- quencher and decreases the removal rate of SOT. The results underscore the role of HCO3- in limiting the persistence of organic pollutants like SOT in sunlit natural waters, and especially in marine and coastal waters.


Assuntos
Bicarbonatos , Poluentes Químicos da Água , Carbonatos , Cinética , Fotólise , Luz Solar , Poluentes Químicos da Água/análise
15.
Theranostics ; 11(9): 4351-4362, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754065

RESUMO

Background: Extracellular vesicles, including exosomes, are secreted by a variety of cell types in the central nervous system. Exosomes play a role in removing intracellular materials from the endosomal system. Alzheimer's disease (AD) is caused by an overproduction or reduced amyloid-beta (Aß) peptide clearance. Increased Aß levels in the brain may impair the exosome-mediated Aß clearance pathway. Therapeutic ultrasound stimulation demonstrated its potential for promoting Aß degradation efficiency in clinical trials. However, the underlying mechanism of ultrasound stimulation is still unclear. Methods: In this study, astrocytes, the most abundant glial cells in the brain, were used for exosome production. Post insonation, exosomes from ultrasound-stimulated HA cells (US-HA-Exo) were collected, nanoparticle tracking analysis and protein analysis were used to measure and characterize exosomes. Neuroprotective effect of US-HA-Exo in oligomeric Aß42 toxicated SH-SY5Y cells was tested. Cellular uptake and distribution of exosomes were observed by flow cytometry and confocal laser scanning microscopy. Focused ultrasound (FUS) with microbubbles was employed for blood-brain-barrier opening to achieve brain-targeted exosome delivery. After US-HA-Exo/FUS treatment, amyloid-ß plaque in APP/PS1 mice were evaluated by Aß immunostaining and thioflavin-S staining. Results: We showed that ultrasound resulted in an almost 5-fold increase in the exosome release from human astrocytes. Exosomes were rapidly internalized in SH-SY5Y cells, and colocalized with FITC-Aß42, causing a decreased uptake of FITC-Aß42. CCk-8 test results showed that US-HA-Exo could mitigate Aß toxicity to neurons in vitro. The therapeutic potential of US-HA-Exo/FUS delivery was demonstrated by a decrease in thioflavin-S-positive amyloid plaques and Aß immuno-staining, a therapeutic target for AD in APP/PS1 transgenic mice. The iTRAQ-based proteomic quantification was performed to gain mechanistic insight into the ultrasound effect on astrocyte-derived exosomes and their ability to alleviate Aß neurotoxicity. Conclusion: Our results imply that US-HA-Exo have the potential to provide neuroprotective effects to reverse oligomeric amyloid-ß-induced cytotoxicity in vitro and, when combined with FUS-induced BBB opening, enable the clearance of amyloid-ß plaques in vivo.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Astrócitos/metabolismo , Exossomos/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Neuroglia/metabolismo , Fármacos Neuroprotetores/metabolismo , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/metabolismo
16.
J Hazard Mater ; 414: 125536, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667804

RESUMO

Propranolol (PRO) is frequently detected in estuarine and coastal waters, which has adverse effects on estuarine and coastal ecosystems. In this study, the effects of halide ions and DOM from estuarine and coastal waters on the photochemical transformation of PRO were investigated. The results demonstrated that the presence of Br- alone exhibited slight effect on photochemical transformation of PRO, while photodegradation rates of PRO increased with the addition of 0.1-0.54 M Cl-. The quenching experiments and the laser flash photolysis experiments together demonstrated the generation of Cl2•- in the photolytic systems. Cl2•- is possibly produced through the charge separation of exciplex of 3PRO* and Cl- rather than via direct oxidation of Cl-. Additional experiments indicated that addition of seawater DOM inhibited the halide ions-sensitized photodegradation rates of PRO, which may be due to the quenching of Cl2•- by phenolic substances in DOM molecules. Compared with pure water, three new photochemical intermediates were identified in the presence of DOM or Cl-. The direct photolysis of PRO mainly reacted by hydroxyl additions, hydroxyl elimination and de-propylation, whereas electron transfer coupled with H-abstraction by Cl2•- and 3DOM* was proposed as the primary role for PRO degradation in the presence of Cl- or DOM.

17.
Food Res Int ; 139: 109945, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509498

RESUMO

Milky tea is popular in many countries and its color is an important sensory property. The effects of black tea infusion on the color of milky tea prepared with non-dairy creamer were investigated. The results showed that the redder black tea infusion produced milky tea with more redness, and the color of milky tea was a pleasant pink when the a* value (redness indicator) was in the range of 6.0-7.0. Correlation analysis revealed that the respective theaflavins (TFs), thearubigins (TRs), thearubigins (TBs), (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid contents significantly correlated with the a* values of milky tea. A series of complementary experiments were performed to elucidate that TFs and EGCG contributed to the redness of milky tea. The color formation was mainly associated with the binding of phenols to the proteins in the non-dairy creamer. These results contribute to understand the mechanism of color formation in milky tea.


Assuntos
Camellia sinensis , Chá , Antioxidantes/análise , Flavonoides/análise , Fenóis/análise
18.
Water Res ; 188: 116568, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137523

RESUMO

Coastal seawater constitutes an important ecosystem receiving inputs of organic micropollutants (OMPs) such as sulfa antibiotics from land-based sources or mariculture activities. It is necessary to investigate photodegradation of OMPs in coastal seawaters for assessing their environmental fate and risks. However, effects of coastal seawater dissolved organic matter (S-DOM) on OMPs photodegradation are largely unknown, given that chemical compositions of S-DOM are different from those of freshwater DOM. Herein, photochemical characteristics of S-DOM extracted from Dalian coastal seawaters were investigated by simulating photochemical experiment adopting sulfachloropyridazine as a case. Results show that S-DOM accelerates the photodegradation mainly through excited triplet-state DOM (3DOM*) with an apparent rate constant (4.43 × 108 M-1 s-1) ten folds of that of freshwater DOM, which is mainly due to much lower phenol contents detected in the S-DOM (0.022 mg-Gallic acid mg-C-1). The S-DOM impacted by mariculture can photogenerate more high-energy 3DOM* than those less impacted by mariculture, further contributing to the high 3DOM* reactivity. The study shows that to accurately predict photolytic persistence of OMPs in field water bodies, it is of significance to determine the second-order reaction rate constants between 3DOM* and target OMPs using DOM extracted from relevant water bodies.


Assuntos
Ecossistema , Poluentes Químicos da Água , Fenóis , Fotólise , Água do Mar
19.
Technol Cancer Res Treat ; 19: 1533033820942298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32856543

RESUMO

BACKGROUND: Liquid-based cytology is one of the most useful methods to diagnose a patient with serous effusion, especially when malignancy is suspected. As an alternative to the use of liquid-based cytology only, the serous effusion can be further processed using the technique of DNA image cytometry, which may augment diagnostic utility. The aim of this study was to compare the diagnostic yields of liquid-based cytology, DNA image cytometry, and both in combination, regardless of serous-effusion etiology. METHODS: We conducted a descriptive study on patients with serous effusions from July 2016 to June 2018. All samples were submitted for liquid-based cytology and DNA image cytometry techniques. We compared the results of cytopathological studies to the final diagnoses. RESULTS: For a total of 798 samples, final diagnoses included 412 (51.6%) malignancies, 280 (35.1.%) inflammatory diseases, and 106 (13.3%) transudative serous effusions. Liquid-based cytology had a more sensitive diagnostic yield than DNA image cytometry did (38.8% vs 30.7%; P < .05), but the combination of both had a higher yield (43.7%; P < .05) compared with that of liquid-based cytology alone. For the 412 malignant serous effusions, diagnostic yields of liquid-based cytology and DNA image cytometry were 73.8% and 59.5%, respectively. The difference in sensitivity was significant (P < .05). Combined liquid-based cytology + DNA image cytometry improved diagnostic yield to 83.3% (P < .05). However, both liquid-based cytology and DNA image cytometry had low diagnostic yields for inflammatory diseases and transudative serous effusions. CONCLUSION: In serous effusion, liquid-based cytology's diagnostic performance is better than that of DNA image cytometry. Application of both techniques can significantly increase diagnostic yield.

20.
Neuropsychologia ; 146: 107549, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32621907

RESUMO

When facing decisions involving trade-offs between smaller, sooner and larger, delayed rewards, people tend to discount the value of future rewards. There are substantial individual differences in this tendency toward temporal discounting, however. One neurocognitive system that may underlie these individual differences is episodic memory, given the overlap in the neural circuitry involved in imagining the future and remembering the past. Here we tested this hypothesis in older adults, including both those that were cognitively normal and those with amnestic mild cognitive impairment (MCI). We found that performance on neuropsychological measures of episodic memory retrieval was associated with temporal discounting, such that people with better memory discounted delayed rewards less. This relationship was specific to episodic memory and temporal discounting, since executive function (another cognitive ability) was unrelated to temporal discounting, and episodic memory was unrelated to risk tolerance (another decision-making preference). We also examined cortical thickness and volume in medial temporal lobe regions critical for episodic memory. Entorhinal cortical thickness was associated with reduced temporal discounting, with episodic memory performance partially mediating this association. The inclusion of MCI participants was critical to revealing these associations between episodic memory and entorhinal cortical thickness and temporal discounting. These effects were larger in the MCI group, reduced after controlling for MCI status, and statistically significant only when including MCI participants in analyses. Overall, these findings suggest that individual differences in temporal discounting are driven by episodic memory function, and that a decline in medial temporal lobe structural integrity may impact temporal discounting.


Assuntos
Desvalorização pelo Atraso/fisiologia , Memória Episódica , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Recompensa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...