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1.
World J Clin Cases ; 12(11): 1940-1946, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660547

RESUMO

BACKGROUND: Direct carotid cavernous fistulas (CCFs) are typically the result of a severe traumatic brain injury. High-flow arteriovenous shunts secondary to rupture of an intracavernous aneurysm, resulting in direct CCFs, are rare. The use of a pipeline embolization device in conjunction with coils and Onyx glue for treatment of direct high-flow CCF resulting from ruptured cavernous carotid artery aneurysm in a clinical setting is not well documented. CASE SUMMARY: A 58-year-old woman presented to our department with symptoms of blepharoptosis and intracranial bruits for 1 wk. During physical examination, there was right eye exophthalmos and ocular motor palsy. The rest of the neurological examination was clear. Notably, the patient had no history of head injury. The patient was treated with a pipeline embolization device in the ipsilateral internal carotid artery across the fistula. Coils and Onyx were placed through the femoral venous route, followed by placement of the pipeline embolization device with assistance from a balloon-coiling technique. No intraoperative or perioperative complications occurred. Preoperative symptoms of bulbar hyperemia and bruits subsided immediately after the operation. CONCLUSION: Pipeline embolization device in conjunction with coiling and Onyx may be a safe and effective approach for direct CCFs.

2.
In Vivo ; 38(3): 1192-1198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688651

RESUMO

BACKGROUND/AIM: Probing brain tumor microvasculature holds significant importance in both basic cancer research and medical practice for tracking tumor development and assessing treatment outcomes. However, few imaging methods commonly used in clinics can noninvasively monitor the brain microvascular network at high precision and without exogenous contrast agents in vivo. The present study aimed to investigate the characteristics of microvasculature during brain tumor development in an orthotopic glioma mouse model. MATERIALS AND METHODS: An orthotopic glioma mouse model was established by surgical orthotopic implantation of U87-MG-luc cells into the mouse brain. Then, optical coherence tomography angiography (OCTA) was utilized to characterize the microvasculature progression within 14 days. RESULTS: The orthotopic glioma mouse model evaluated by bioluminescence imaging and MRI was successfully generated. As the tumor grew, the microvessels within the tumor area slowly decreased, progressing from the center to the periphery for 14 days. CONCLUSION: This study highlights the potential of OCTA as a useful tool to noninvasively visualize the brain microvascular network at high precision and without any exogenous contrast agents in vivo.


Assuntos
Neoplasias Encefálicas , Modelos Animais de Doenças , Glioma , Tomografia de Coerência Óptica , Animais , Tomografia de Coerência Óptica/métodos , Camundongos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Linhagem Celular Tumoral , Humanos , Microvasos/diagnóstico por imagem , Microvasos/patologia , Imageamento por Ressonância Magnética/métodos , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/patologia , Angiografia/métodos
3.
Trends Biotechnol ; 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38160083

RESUMO

China's newly issued genome-edited crop safety assessment guidelines do not entirely deviate from the existing genetically modified regulatory regimes. However, there is an urgent need to reform the genome-edited regulatory framework based on scientific values and a novel regulatory philosophy that balances diverse values to enhance public trust.

4.
Nat Prod Res ; : 1-10, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37395467

RESUMO

The molecularly imprinted polymer was synthesized using 3-aminopropylthiosilane-methacrylic acid monomer (APTES-MAA) as the functional monomer and 10-hydroxycamptothecin (HCPT) as the template, based on computer simulation. The hybrid molecularly imprinted polymers (HMIPs) were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, particle size measurement, scanning electron microscopy and energy dispersive X-ray spectroscopy. It has been shown that HMIPs are irregularly shaped and porous, with particle sizes ranging mainly from 130 to 211 nm. At 298 K, the HMIPs exhibit a maximum adsorption capacity of 8.35 mg·g-1 for HCPT and demonstrate good adsorption specificity (α = 5.38). The pseudo-second-order reaction mechanism suggests that the equilibrium adsorption capacity of HCPT on HMIPs is 8.11 mg·g-1. Finally, HCPT was successfully separated and enriched from the extract of Camptotheca acuminata Decne. seeds using HMIPs.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37276100

RESUMO

Automated exercise assessment is of great importance for patients under rehabilitation exercise who require professional guidance. Among the existing approaches, the skeleton-based assessment model that classifies the correctness of the exercise has attracted much attention due to its relative ease of implementation and convenience in use. However, there are two problems with this approach. The first problem is its sensitivity to the orientation of the human skeleton. To solve this problem, we propose a novel rotation-invariant descriptor, the dot product matrix of the human skeleton, and prove mathematically that this descriptor discards only the orientation message that we do not expect while preserving all other useful information. Lack of feedback from the system is the second problem, because the exercisers do not know which parts of their exercises are incorrect. Therefore, we develop a visualization method for our system based on Gradient-Weighted Class Activation Mapping (Grad-CAM) and an quantitative metric called Overlap Ratio (OvR) to measure the quality of the visualization result. To demonstrate the effect of our method, we conduct experiments on two public datasets and a self-generated push-up dataset. The experimental results show that our rotation-invariant descriptor can achieve absolute robustness to orientation even under severe angle perturbations. In terms of accuracy and OvR, our method even outperforms previous works in most cases, indicating that the rotation-invariant descriptor helps the assessment model to extract more stable features. The visualization results are also informative to correct the movements; some examples are presented in this paper. The code of this paper and our push-up dataset are publicly available at https://github.com/Kelly510/RehabExerAssess.


Assuntos
Algoritmos , Reconhecimento Automatizado de Padrão , Humanos , Reconhecimento Automatizado de Padrão/métodos , Terapia por Exercício , Esqueleto
6.
J Sep Sci ; 46(15): e2300098, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37246933

RESUMO

In recent years, it has been found that changing ambient conditions (CO2 /N2 , temperature, pH) can trigger a switchable phase transition of deep eutectic solvents, and such solvents are known as responsive deep eutectic solvents. In this work, we present the development history, properties, and preparation of responsive deep eutectic solvents, followed by the application of responsive deep eutectic solvents in the extraction and separation of bioactive compounds are presented. Importantly, the mechanism of responsive deep eutectic solvents in the extraction of bioactive compounds is discussed. Finally, the challenges and prospects of responsive deep eutectic solvents in the extraction and separation of bioactive compounds are proposed. Responsive deep eutectic solvents are considered green and efficient solvents. Some methods for extraction and separation of bioactive compounds by responsive deep eutectic solvents can increase the possibility of recycling the deep eutectic solvents, and provide higher efficiency in the extraction and separation field. It is hoped that this will provide a reference for the green and sustainable extraction and separation of various bioactive compounds.


Assuntos
Solventes Eutéticos Profundos , Solventes/química
7.
Psychol Res Behav Manag ; 16: 829-839, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36945310

RESUMO

Background: The present study investigated the applicability of the Cognitive Emotion Regulation Questionnaire (CERQ) in the Chinese community elderly and explored the influence of cognitive emotion regulation strategies on late-life depression. Methods: A total of 367 community elderly aged 60-94 were deemed eligible and completed CERQ, the Perceived Stress Scale-10, the Geriatric Depression Questionnaire-15, and the State Anxiety Inventory. Confirmatory factor analysis was adopted to verify the 9-factor structure of CERQ. Cronbach's α coefficient, Ω coefficient and split-half reliability were used to test the internal consistency of CERQ. Pearson correlations among scores of CERQ and other scales were calculated to examine its convergent validity. In addition, a structural equation model was used to further examine the effect of cognitive emotion regulation strategies on the association between perceived stress and late-life depression. Results: All the fitting indexes of CERQ's 9-factor model met the criterion (χ 2/df= 2.26, CFI= 0.916, TLI= 0.904, RMSEA= 0.052). For the total score of CERQ, the Cronbach's α coefficient and Ω coefficient were both 0.90, and the split-half reliability was 0.74. For the nine subscales, the α coefficients ranged from 0.66 to 0.88, and the Ω coefficients ranged from 0.69 to 0.88. Significant positive correlations were found between the maladaptive dimension of CERQ and other scales (all p < 0.001). The maladaptive emotion regulation strategies indirectly affected the effect of perceived stress on late-life depression (effect size was 21.57%). Conclusion: With good reliability and factor validity, the CERQ showed good applicability in the Chinese elderly population. The influence of perceived stress on depression in the elderly was mediated by maladaptive emotion regulation strategies.

8.
Nat Metab ; 4(10): 1369-1401, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36217034

RESUMO

The activity of 5'-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.


Assuntos
Insulinas , Inanição , Humanos , Masculino , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Lisossomos/metabolismo , Inanição/metabolismo , Adenosina Trifosfatases/metabolismo , Caenorhabditis elegans , Monofosfato de Adenosina/metabolismo , Frutose/metabolismo , Insulinas/metabolismo
9.
Opt Express ; 30(20): 35854-35870, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258527

RESUMO

Optical coherence tomography angiography (OCTA) images suffer from inevitable micromotion (breathing, heartbeat, and blinking) noise. These image artifacts can severely disturb the visibility of results and reduce accuracy of vessel morphological and functional metrics quantization. Herein, we propose a multiple wavelet-FFT algorithm (MW-FFTA) comprising multiple integrated processes combined with wavelet-FFT and minimum reconstruction that can be used to effectively attenuate motion artifacts and significantly improve the precision of quantitative information. We verified the fidelity of image information and reliability of MW-FFTA by the image quality evaluation. The efficiency and robustness of MW-FFTA was validated by the vessel parameters on multi-scene in vivo OCTA imaging. Compared with previous algorithms, our method provides better visual and quantitative results. Therefore, the MW-FFTA possesses the potential capacity to improve the diagnosis of clinical diseases with OCTA.


Assuntos
Artefatos , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Reprodutibilidade dos Testes , Algoritmos , Angiografia/métodos
10.
Child Abuse Negl ; 125: 105485, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35026440

RESUMO

OBJECTIVE: Childhood trauma (CT) is a well-recognized distal risk factor for depression. Previous studies suggested that the psychological mechanism of the impact of childhood trauma on depression may be attributed to some mediators such as daily stress and psychological resilience. This study aimed to assess how daily stress and resilience affect the relationship between childhood trauma and depression in adult clinical context. METHOD: In this cross-section survey, a total of 569 clinical patients with psychological disorders completed a series of psychological scales such as the Childhood Trauma Questionnaire (CTQ), the Center for Epidemiologic Studies Depression Scale (CESD), the Perceived Stress Scale (PSS) and Connor-Davidson Resilience Scale (CD-RISC). To show the relationship among childhood trauma, psychological resilience, daily stress and depression, structural equation modeling (SEM) was performed. RESULTS: The results indicated that psychological resilience and daily stress partially mediated the relationship between childhood trauma and depressive symptoms. Childhood trauma not only exerted direct effect on depressive symptoms, but also had indirect effect through the mediation pathway (resilience â†’ daily stress) on depressive symptoms. The chain mediation pathway through resilience and daily stress was weighted 43.31%. CONCLUSIONS: The study provides novel evidence on the underlying process between childhood trauma and depression. The distal factor childhood trauma can influence the latter depression by the chain effect of psychological resilience and daily stress. Therefore, some clinical interventions to improve psychological resilience to carry off daily stress are the way to reduce the impact of childhood trauma on depression.


Assuntos
Experiências Adversas da Infância , Resiliência Psicológica , Adulto , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Humanos , Estresse Psicológico , Inquéritos e Questionários
11.
Artigo em Inglês | MEDLINE | ID: mdl-34742774

RESUMO

Aggressive behaviors are prevalent among patients with Borderline Personality Disorder (BPD). Neuroimaging studies have linked aggression in BPD patients to neurochemical, structural, functional, and metabolic alterations in various brain regions, especially in frontal-limbic areas. This systematic review summarizes current neuroimaging results on aggression among BPD patients and provides an overview of relevant brain mechanisms. A systematic search of PubMed and Web of Science databases, in addition to manual check of references, identified thirty-two eligible articles, including two magnetic resonance spectrum (MRS), thirteen structural magnetic resonance imaging (sMRI), six functional magnetic resonance imaging (fMRI), and eleven positron emission tomography (PET) studies. The reviewed studies have highlighted the abnormalities in prefrontal cortices and limbic structures including amygdala and hippocampus. Less studies have zoomed in the roles of parietal and temporal regions or taken a network perspective. Connectivity studies have shed light on the importance of the frontal-limbic interactions in regulating aggression. Conflicted findings might be attributed to disparity in controlling gender, anatomical subdivisions, and comorbidities, which shall be considered in future studies.


Assuntos
Agressão/fisiologia , Transtorno da Personalidade Borderline/patologia , Neuroimagem , Tonsila do Cerebelo/patologia , Encéfalo/patologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/patologia
12.
Microorganisms ; 9(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34835442

RESUMO

YgfY(SdhE/CptB) is highly conserved while has controversial functions in bacteria. It works as an antitoxin and composes a type IV toxin-antitoxin system with YgfX(CptA) typically in Escherichia coli, while functions as an flavinylation factor of succinate dehydrogenase and fumarate reductase typically in Serratia sp. In this study, we report the contribution of YgfY in Shewanella oneidensis MR-1 to tolerance of low temperature and nitrite. YgfY deficiency causes several growth defects of S. oneidensis MR-1 at low temperature, while YgfX do not cause a growth defect or morphological change of S. oneidensis MR1-1 and E. coli. YgfY do not interact with FtsZ and MreB nor with YgfX examined by bacterial two-hybrid assay. YgfY effect on growth under low temperature is not attributed to succinate dehydrogenase (SDH) because a mutant without SDH grows comparably with the wild-type strain in the presence of succinate. The ygfY mutant shows impaired tolerance to nitrite. Transcription of nitrite reductase and most ribosome proteins is significantly decreased in the ygfY mutant, which is consistent with the phenotypes detected above. Effects of YgfY on growth and nitrite tolerance are closely related to the RGXXE motif in YgfY. In summary, this study demonstrates pleiotropic impacts of YgfY in S. oneidensis MR-1, and sheds a light on the physiological versatility of YgfY in bacteria.

13.
Sci Rep ; 11(1): 16628, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404887

RESUMO

This study was aimed to investigate whether BPD patients showed impaired impulse inhibition of emotional and non-emotional stimuli and to explore relevant neuroelectrophysiological mechanisms. A total of 32 BPD patients and 32 matched healthy controls were recruited. Self-reported scales were used to measure psychiatric symptoms. The event-related potentials (ERPs) were recorded when subjects were performing neutral and emotional Stop Signal Task (SST). Group differences in self-reported scores, behavioral variables and ERPs were compared. The BPD group scored significantly higher on impulsivity, severity of BPD symptoms, levels of depression and anxiety than the control group. In neutral SST, no significant group differences were detected in the amplitude and latency of ERPs components induced. In emotional SST, the P2 amplitude of negative emotion was significantly larger than that of neutral emotion in Go trials. In Stop trials, the P2 amplitude of BPD group was significantly smaller than that of control group, and the N2 amplitude of BPD group was significantly greater than that of control group. BPD patients showed impaired inhibition of emotional stimuli rather than non-emotional stimuli. The deficits of emotional impulse control mainly exhibit at the early attention, stimulus evaluation and conflict detection stages.


Assuntos
Transtorno da Personalidade Borderline/psicologia , Emoções , Comportamento Impulsivo , Adulto , Estudos de Casos e Controles , Potenciais Evocados , Feminino , Humanos , Masculino
14.
Hum Brain Mapp ; 42(16): 5217-5229, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34328676

RESUMO

Abnormal fronto-parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n-back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n-back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2-back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2-back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d' of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.


Assuntos
Conectoma , Transtorno Depressivo Maior/fisiopatologia , Córtex Pré-Frontal Dorsolateral/fisiopatologia , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiopatologia , Lobo Parietal/fisiopatologia , Adolescente , Adulto , Conectoma/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Córtex Pré-Frontal Dorsolateral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Adulto Jovem
15.
J Mater Chem B ; 9(27): 5547-5559, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34165487

RESUMO

Sonodynamic therapy has attracted wide attention as a noninvasive therapy due to deep tissue penetration. However, majority sonosensitizers often suffer from poor physiological stability, rapid blood clearance and nonspecific targeting, which seriously hinders their further practical applications. Inspired by the concept of active targeting drug delivery, both dual-functional chemo-drug pemetrexed (PEM, emerges an innate affinity toward the folate receptor) and amphiphilic d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected to be covalently linked by an esterase-responsive ester linkage. The synthesized self-targeting TPGS-PEM prodrug and indocyanine green (ICG) as functional motifs can be self-assembled into a TPGS-PEM-ICG nanoplatform within an aqueous medium. The TPGS-PEM-ICG nanoplatform with outstanding structural and physiological stability not only protects the sonosensitizer from reticular endothelial system clearance but also achieves active targeting drug delivery and efficient tumor enrichment. Moreover, TPGS-PEM-ICG nanoplatform can selectively recognize tumor cells and then realize on-demand drug burst release by multiple stimuli of internal lysosomal acidity, esterase and external ultrasound, which guarantee low side effects toward normal tissues and organs. It is also worth noting that our nanoplatform exhibits protruding tumor enrichment under the precise guidance of photoacoustic/fluorescence imaging. Further in vitro and in vivo experimental results well confirmed that the TPGS-PEM-ICG nanoplatform possesses enhanced chemo-sonodynamic effects. Interestingly, the highly toxic reactive oxygen species can remarkably reduce the blood oxygen saturation signal of the tumor microenvironment via precise, multifunctional and high-resolution photoacoustic imaging. Taken together, the TPGS-PEM-ICG nanoplatform can be expected to hold enormous potential for diagnosis, prognosis and targeted therapy for tumor.


Assuntos
Antineoplásicos/farmacologia , Verde de Indocianina/química , Nanopartículas/química , Técnicas Fotoacústicas , Pró-Fármacos/farmacologia , Terapia por Ultrassom , Vitamina E/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Imagem Óptica , Tamanho da Partícula , Pró-Fármacos/química , Vitamina E/química
16.
Depress Anxiety ; 38(1): 28-39, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32720464

RESUMO

BACKGROUND: Previous studies suggested that childhood trauma is an important etiologic factor for the development of borderline personality disorder (BPD). Moreover, insecure attachment and maladaptive emotion regulation (ER) might be related to childhood trauma and BPD. This study was aimed to explore the relationships among childhood trauma, insecure attachment, maladaptive ER, and BPD features. METHODS: A cohort of 637 patients with psychological disorders completed a series of psychometric instruments such as the Personality Diagnostic Questionnaire-4+ (PDQ-4+), the 23-Item Borderline Symptom List, the Childhood Trauma Questionnaire, the Attachment Style Questionnaire, and the Cognitive Emotion Regulation Questionnaire. The path analyses were conducted to investigate the experience-driven model that whether insecure attachment and maladaptive ER could mediate the relationship between childhood trauma and BPD features. The random forest regression was performed to select variables that contribute significantly to BPD features, which variables would be incorporated into the data-driven model to further confirm the experience-driven model. RESULTS: Both the experience-driven model and the data-driven model verified that there were three significant mediation pathways (childhood trauma → insecure attachment/maladaptive ER → BPD features, childhood trauma → insecure attachment → maladaptive ER → BPD features; all p < .05), and the most weighted mediation pathway by which childhood trauma influencing the BPD features was through insecure attachment and then through maladaptive ER (weighted 53.16%). CONCLUSION: The influence of childhood trauma on BPD features was mainly mediated by the combination of insecure attachment and maladaptive emotion regulation.


Assuntos
Transtorno da Personalidade Borderline , Regulação Emocional , Transtorno da Personalidade Borderline/epidemiologia , Humanos , Personalidade , Inquéritos e Questionários
17.
Int J Pharm ; 594: 120184, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340597

RESUMO

D-a-tocopheryl polyethylene glycol succinate (TPGS) as a FDA-approved safe adjuvant has shown an excellent application in the targeting delivery of antitumor drugs and overcoming multidrug resistance. Beside, TPGS can result in apoptogenic activity toward many tumor types because it can induce mitochondrial dysfunction. Therefore, TPGS can serve as an antineoplastic agent. However, the current research on the selective antitumor activity of TPGS is ignored. To reveal the issue, herein we develop a mitochondria-targeting drug-free TPGS nanomicelles with the hydrodynamic diameter of about 100 nm and outstanding serum stability by weak interaction-driven self-assembly of the amphiphilic TPGS polymer. Moreover, such drug-free TPGS nanomicelles intravenously injected into tumor-bearing mice exhibit long blood circulation time, superior tumor enrichment, and inhibit the tumor growth via inducing excessive reactive oxygen species (ROS) generation within tumor cells. Further in vitro and in vivo researches jointly demonstrate that drug-free TPGS nanomicelles have more significant antitumor effect on HeLa cells compared with that of other tumor cells. On the contrary, drug-free TPGS nanomicelles display the low toxicity toward normal cells and tissues. Taken together, these new findings confirm that TPGS drug-free nanomicelles represent simple, multifunctional, safe, and efficient antineoplastic agents, which can be expected to bring new light on the development of drug-free polymers for tumor therapy.


Assuntos
Antineoplásicos , Polietilenoglicóis , Animais , Antineoplásicos/farmacologia , Morte Celular , Linhagem Celular Tumoral , Células HeLa , Humanos , Camundongos , Micelas , Mitocôndrias , Espécies Reativas de Oxigênio , Vitamina E
18.
Int Forum Allergy Rhinol ; 10(5): 646-655, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32052917

RESUMO

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces reactive oxygen species (ROS) involved in oxidative stress and signal transduction. Recent studies have suggested that NADPH oxidase is associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this study was to detect the expression of NADPH oxidase subunits and 4-hydroxynonenal (4-HNE) in nasal polyp tissue and normal nasal mucosa, in order to explore the possible role played by NADPH oxidase in the pathogenesis of CRSwNP. METHODS: Thirteen patients with CRSwNP and 9 normal control subjects were selected to participate in this study, in which we evaluated the expression of different NADPH oxidase subunits (gp91phox , p67phox , p47phox , and p22phox ) in nasal polyp (NP) tissue and control mucosa by Western blotting and real-time polymerase chain reaction (PCR). Immunohistochemistry and immunofluorescence staining were used to detect expression of the p67phox subunit and 4-HNE in NP tissue and normal nasal mucosa. RESULTS: Western blot and real-time PCR results showed that p67phox expression was significantly increased in NP tissue when compared with its expression in control mucosa (p = 0.004). p67phox was expressed in the eosinophils and neutrophils found in NP tissue, but not in the macrophages. Additionally, the levels of 4-HNE expression were also significantly increased in NP tissue when compared with control mucosa (p = 0.001). CONCLUSION: The levels of p67phox messenger RNA (mRNA) and protein as well as 4-HNE were both upregulated in NP tissue, suggesting that p67phox and oxidative stress play roles in the pathogenesis of CRSwNP.


Assuntos
NADPH Oxidases/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Idoso , Aldeídos/metabolismo , Doença Crônica , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Pólipos Nasais/patologia , Neutrófilos/metabolismo , Estresse Oxidativo , Fosfoproteínas/metabolismo , Rinite/patologia , Sinusite/patologia
19.
J Allergy Clin Immunol Pract ; 8(5): 1574-1581.e4, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31891823

RESUMO

BACKGROUND: Nasal nitric oxide (nNO) has been evaluated in patients with chronic rhinosinusitis with and without nasal polyps. However, nNO levels in patients with allergic rhinitis (AR) and nonallergic rhinitis (NAR) have shown conflicting results in previous studies. OBJECTIVE: To evaluate the value of nNO in diagnosing AR and NAR and the impact of absence or presence of sinus inflammation (SI). METHODS: A total of 173 consecutive patients scanned with high-resolution computed tomography (CT) and 46 normal controls (NCs) were included in our study. Patients were evaluated according to their medical history, nasal symptoms, endoscopic examinations, and skin prick test results. On the basis of CT scans (Lund-Mackay score >2), all patients were subgrouped as AR with SI (ARwSI) and AR without SI (ARsSI), or NAR with SI (NARwSI) and NAR without SI (NARsSI). nNO levels were measured with the NIOX, and eosinophils in nasal smears were evaluated simultaneously. Receiver-operating characteristic analysis was performed for differential diagnosis of AR, NAR, and subgroups. RESULTS: Ninety-four patients were diagnosed with AR and 79 patients with NAR. The levels of nNO were significantly higher in patients with AR and in NCs compared with patients with NAR (939 ± 335 in AR and 813 ± 272 in NCs vs 670 ± 188 in NAR; P < .001 for both), and significantly higher in patients with AR compared with NCs (P < .05). On the basis of sinus CT scans, 49% patients with AR (46 of 94) were defined as ARwSI and 51% patients with NAR (40 of 79) were defined as NARwSI. Patients with ARsSI showed the highest nNO levels (1180 ± 289) compared with other subgroups (P < .001), and patients with NARwSI showed the lowest nNO levels (522 ± 120) compared with other subgroups (P < .001). nNO could be used to discriminate AR, NAR, and subgroups with acceptable sensitivity and specificity. Moreover, patients with nasal smear eosinophilia had lower nNO levels than did patients with NAR (P < .05). CONCLUSIONS: nNO levels are different between patients with ARwSI/ARsSI and NARwSI/NARsSI, and may be used to discriminate these phenotypes.


Assuntos
Rinite Alérgica , Rinite , Sinusite , Humanos , Inflamação , Óxido Nítrico , Rinite/diagnóstico , Rinite Alérgica/diagnóstico , Sinusite/diagnóstico
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