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1.
Anal Chem ; 95(38): 14165-14168, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37702743

RESUMO

ß-Glucuronidase (GLU) is a hallmark enzyme for many malignant tumors, but bioluminescence (BL) probes that enable GLU imaging in vivo have not been reported. Herein, we rationally designed the BL probe Glc-Luc to address this issue. In vitro results demonstrated the specific responsiveness of Glc-Luc toward GLU with a calculated catalytic efficiency (kcat/Km) of 0.0109 µM-1 min-1 and a limit of detection (LOD) of 1.39 U/mL. Moreover, Glc-Luc rendered 3.1-fold and 15.9-fold higher BL intensities over the control groups in cell lysates and tumor-bearing mice, respectively. We anticipate that Glc-Luc could be further applied for the sensitive diagnosis of GLU-related diseases.


Assuntos
Glucuronidase , Neoplasias , Animais , Camundongos , Neoplasias/diagnóstico por imagem , Diagnóstico por Imagem , Catálise , Testes Imunológicos
2.
Angew Chem Int Ed Engl ; 62(32): e202306427, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347163

RESUMO

Staphylococcus aureus (S. aureus) is able to hide within host cells to escape immune clearance and antibiotic action, causing life-threatening infections. To boost the therapeutic efficacy of antibiotics, new intracellular delivery approaches are urgently needed. Herein, by rational design of an adamantane (Ada)-containing antibiotic-peptide precursor Ada-Gly-Tyr-Val-Ala-Asp-Cys(StBu)-Lys(Ciprofloxacin)-CBT (Cip-CBT-Ada), we propose a strategy of tandem guest-host-receptor recognitions to precisely guide ciprofloxacin to eliminate intracellular S. aureus. Via guest-host recognition, Cip-CBT-Ada is decorated with a ß-cyclodextrin-heptamannoside (CD-M) derivative to yield Cip-CBT-Ada/CD-M, which is able to target mannose receptor-overexpressing macrophages via multivalent ligand-receptor recognition. After uptake, Cip-CBT-Ada/CD-M undergoes caspase-1 (an overexpressed enzyme during S. aureus infection)-initiated CBT-Cys click reaction to self-assemble into ciprofloxacin nanoparticle Nano-Cip. In vitro and in vivo experiments demonstrate that, compared with ciprofloxacin or Cip-CBT-Ada, Cip-CBT-Ada/CD-M shows superior intracellular bacteria elimination and inflammation alleviation efficiency in S. aureus-infected RAW264.7 cells and mouse infection models, respectively. This work provides a supramolecular platform of tandem guest-host-receptor recognitions to precisely guide antibiotics to eliminate intracellular S. aureus infection efficiently.


Assuntos
Ciclodextrinas , Infecções Estafilocócicas , Animais , Camundongos , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
3.
J Behav Addict ; 12(2): 471-479, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37267086

RESUMO

Background and aims: The Pavlovian-to-instrumental transfer (PIT) effect is a phenomenon that Pavlovian conditioned cues that could influence one's instrumental behavior. In several substance and behavioral addictions, such as tobacco use disorder and gambling disorder, addiction-related cues could promote independently trained instrumental drug-seeking/drug-taking behaviors, indicating a specific PIT effect. However, it is unclear whether Internet gaming disorder (IGD) would show a similar change in PIT effects as other addictions. The study aimed to explore the specific PIT effects in IGD. Methods: We administrated a PIT task to individuals with IGD (n = 40) and matched health controls (HCs, n = 50), and compared the magnitude of specific PIT effects between the two groups. The severity of the IGD symptoms was assessed by the Chinese version 9-item Internet Gaming Disorder Scale (IGDS) and the Internet Addiction Test (IAT). Results: We found that: (1) related to the HCs group, the IGD group showed enhanced specific PITgame effects, where gaming-related cues lead to an increased choice rate of gaming-related responses; (2) in the IGD group, the magnitude of specific PITgame effects were positively correlated with IAT scores (rho = 0.39, p = 0.014). Discussion and Conclusions: Individuals with IGD showed enhanced specific PIT effects related to HCs, which were associated with the severity of addictive symptoms. Our results highlighted the incentive salience of gaming-related cues in IGD.


Assuntos
Comportamento Aditivo , Jogo de Azar , Jogos de Vídeo , Humanos , Transtorno de Adição à Internet , Comportamento Aditivo/diagnóstico , Sinais (Psicologia) , Internet
4.
Nano Lett ; 23(13): 6178-6183, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37363812

RESUMO

Apoptosis, with a hallmark of upregulated protease Caspase-3, has been frequently imaged with various probes to reveal the therapeutic efficiencies of different drugs. However, activatable molecular probes with programmable self-assembling behaviors that enable enhanced T1-weighted magnetic resonance imaging (MRI) of apoptosis remain scarce. Herein, taking advantage of a CBT-Cys click reaction, we rationally designed a Caspase-3-activatable self-assembling probe Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys(DOTA(Gd))-CBT (DEVDCS-Gd-CBT) for apoptosis imaging in vivo. After Caspase-3 cleavage in apoptotic cells, DEVDCS-Gd-CBT underwent CBT-Cys click reaction to form a cyclic dimer, which self-assembled into Gd nanoparticles. With this probe, enhanced T1-weighted MR images of apoptosis were achieved at low magnetic fields in vitro, in cis-dichlorodiamineplatinum-induced apoptotic cells and in tail-amputation-simulated apoptotic zebrafish. We anticipate that the smart probe DEVDCS-Gd-CBT could be applied for T1-weighted MRI of apoptosis-related diseases in the clinic in the future.


Assuntos
Gadolínio , Nanopartículas , Animais , Caspase 3 , Peixe-Zebra , Imageamento por Ressonância Magnética/métodos , Apoptose , Meios de Contraste
5.
Artigo em Inglês | MEDLINE | ID: mdl-37271367

RESUMO

AIMS: This study aimed to identify gray/white matter volume (GMV/WMV) alterations in Internet Gaming Disorder (IGD), with a special focus on the subregions of the mesocorticolimbic dopaminergic system and their clinical association. RESULTS: Compared with healthy controls, IGDs showed bigger GMV in the bilateral caudate and the left nucleus accumbens (NAc), and bigger WMV in the inferior parietal lobule. The comparison of regions of interest (ROI) confirmed increased GMV in the bilateral caudate (including the dorsal anterior, body, and tail) and the left core of NAc in IGD, but no significant WMV alterations in the mesocorticolimbic dopaminergic system. GMVs in the left lateral orbital gyrus of orbitofrontal cortex (OFC) were associated with craving for games, while GMVs in the left anterior insula, right NAc, right caudate, and right OFC were associated with self-control in IGD. CONCLUSIONS: IGD was accompanied by changed GMV, but not WMV, in the mesocorticolimbic dopaminergic system. GMV in the mesocorticolimbic dopaminergic system may contribute to impaired self-control and craving in IGD.


Assuntos
Comportamento Aditivo , Jogos de Vídeo , Substância Cinzenta , Transtorno de Adição à Internet , Imageamento por Ressonância Magnética , Encéfalo , Córtex Pré-Frontal , Mapeamento Encefálico , Internet
6.
ACS Cent Sci ; 9(12): 2251-2256, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38161373

RESUMO

Autophagy plays a crucial role in tumorigenesis and progression, but current approaches to visualize it in vivo show limited precision due to their single-analyte-responsive mode. Hence, by simultaneously employing dual autophagy enzymes Atg4B and cathepsin B to trigger the in situ formation of luciferin, we herein propose a strategy for precise autophagy bioluminescence imaging. An Atg4B-responsive peptide Ac-Thr-Phe-Gly-d-Cys (TFGC) and a cathepsin B-activatable compound Ac-Lys-Gly-Arg-Arg-CBT (KGRR-CBT) were rationally designed. During tumor autophagy, these two compounds were uptaken by cancer cells and cleaved by their corresponding enzymes to yield d-cysteine and 2-cyano-6-aminobenzothiazole, respectively, which underwent a CBT-Cys click reaction to yield d-aminoluciferin, turning the bioluminescence "on". The responsiveness of these two compounds toward the two enzymes was tested in vitro, and the ability to turn bioluminescence "on" was validated in living cancer cells and in vivo. We anticipate that our precise autophagy imaging strategy could be further applied for the diagnosis of autophagy-related diseases in the near future.

7.
Front Psychol ; 13: 906171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304870

RESUMO

This study aimed to preliminary examine the psychometric properties of the Chinese version 96-item VIA Inventory for Youth (VIA Youth-96) by analyzing the internal consistency, factorial validity, and criterion validity, and to examine the age-related changes in character strengths (CSs) among adolescents. The sample consisted of 959 adolescents aged 10-17 (49.5% boys). Participants completed the Chinese version VIA Youth-96, along with the Perceived Parental Autonomy Support Scale, and questionnaires assessing life satisfaction and self-efficacy online. The Chinese version VIA Youth-96 showed a good fit for the original four-factor structure, and CS scores were significantly correlated with life satisfaction and self-efficacy indicating a good criterion validity of the scale. The internal consistency was 0.54-0.86 for subscales. Moreover, this study revealed significant age-related changes in CSs among adolescents, eight CSs significantly linearly declined by age. These results suggested that the Chinese version VIA Youth-96 is a valid tool for assessing CSs in adolescents and that CSs are declined linearly by age during adolescence.

8.
Adv Healthc Mater ; 11(23): e2201916, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36148589

RESUMO

Chemotherapy has remained an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies are proposed to address these issues, yet their therapeutic outcomes are still far from satisfactory. Thus, it is urgent to develop novel strategies to promote tumor chemosensitivity while reducing toxic side effects of chemotherapeutics. Herein, employing a rationally designed peptide conjugate Nap-Phe-Phe-Lys(SA-AZD8055)-Tyr(H2 PO3 )-OH (Nap-AZD-Yp), a novel approach of simultaneous intracellular nanofiber formation and autophagy inducer release is proposed for selectively sensitizing tumor to chemotherapy. Upon sequential catalyses of alkaline phosphatase and carboxylesterase, Nap-AZD-Yp undergoes nanosphere-to-nanofiber transition accompanied by autophagy inducer AZD8055 release in cancer cells. Cell experiments show enhanced endocytosis of anticancer drug doxorubicin and inhibition of cell migration due to the intracellular nanofiber formation. The released AZD8055 further activates excessive autophagy of cancer cells, sensitizing them to chemotherapy. Animal experiment results suggest Nap-AZD-Yp can significantly enhance the therapeutic effects of doxorubicin on tumors while mitigate its toxic adverse effects on normal tissues. It is anticipated that the "smart" concept in this work c be widely employed to develop novel combinational therapies for the treatment of cancers and other diseases in near future.


Assuntos
Autofagia , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Doxorrubicina/farmacologia
9.
PLoS Pathog ; 18(9): e1010807, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36067210

RESUMO

Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.


Assuntos
COVID-19 , Inibidores de Prolil-Hidrolase , Animais , Antivirais , Cricetinae , Hipóxia , Pulmão/patologia , Mesocricetus , Oxigênio , RNA Viral , SARS-CoV-2
10.
Front Psychol ; 13: 961387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059774

RESUMO

Employees in high-risk occupations are exposed to tremendous work acute stress or prolonged stress disorders that are likely to undermine the health and organizational effectiveness. Based on positive psychology, courage which refers to behavioral approach despite the experience of fear could buffer the negative effects on stress. However, there is little known about the mechanisms by which courage decreases the risk of stress. Motivational systems may play an underlying role in this process, as behavioral inhibition system (BIS) is inhibited and behavioral activation system (BAS) is evoked by risk or threat. The current study aimed to examine the mediating effects of behavioral inhibition and activation on the relationship between courage and stress in the high-risk occupations. This study recruited 1,761 high-risk employees aged from 18 to 27 (M = 19.32; SD = 4.14) with a cluster sampling method who completed Courage Measure (CM), the BIS/BAS Scales and the Psychological Stress Evaluation Test (PSET). The correlation and mediation analyses examined the inter-variable correlations as well as the underlying mechanism between courage and stress. The results support the hypothesis and reveal that the behavioral inhibition mediates the association between courage and stress (B indirect = -0.02, p < 0. 01, 95%CI = -0.03 to -0.003). The behavioral activation of fun seeking mediates the association between courage and stress as well (B indirect = -0.04, p < 0. 01, 95%CI = -0.058 to -0.029). These findings suggest that behavioral inhibition and activation of fun seeking play imperative mechanism underpinning the buffering effect of courage on stress. Other theoretical and applied implications for desensitizing stress in the high-risk occupations are discussed.

11.
Psychol Res Behav Manag ; 15: 1783-1796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860202

RESUMO

Background: Employees in high-risk occupations are exposed to tremendous work stress that hinders organizational effectiveness and personal mental health. Based on positive psychology, courage can be considered a protective factor that buffers the adverse effect of high-risk surroundings on employees. However, little is known about the way courage is simulated or evaluated in response to safety concerns. Virtual reality (VR) is an accessible tool for courage simulation due to its immersive qualities, presence and interactive features and may provide a promising pathway to achieve a scientific, accurate and ecologically valid evaluation of high-risk employees. Methods: The sample consisted of 51 high-risk employees who were recruited voluntarily. Before and after experiencing the VR courage scenarios, the participants completed the VR features questionnaire, the Physical Courage at Work Scale (PCWS), the Courage Measure (CM), and the Positive and Negative Affect Scale (PANAS). During the process of watching the VR courage scenarios, the participants' heart rate and skin conductance at resting-state baseline and during virtual courage scenarios were recorded through HTC VIVE Pro Eye and BioGraph Infiniti 8. Results: The results support the hypothesis and reveal that the interaction, immersion and presence scores of the scenarios were all significantly higher than the median 4 points. The score for the CM in the posttest was significantly higher than that in the pretest. The scared and afraid scores for the posttest were significantly higher than those for the pretest. The heart rate and skin conductance of each scenario showed an increase compared with the baseline. The Pearson's correlation between physiological indicators and the score of the PCWS was 0.28~0.54. Conclusion: This study developed virtual courage for high-risk occupations based on well-established theory and VR technology. Experimental data revealed that the paradigm conformed to the requirements of VR features and was able to activate fear and evoke the quality of courage. Thus, the virtual courage paradigms have good validity in simulating scenarios for high-risk employees, which might accelerate organizational effectiveness while buffering working stress.

12.
Psicol Reflex Crit ; 35(1): 16, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641705

RESUMO

Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10-12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r = -0.14 to -0.3, p < 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14-22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution (ß = -0.34 to -0.14 for self-regulation, perseverance, zest, humility, and leadership; ß = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.

13.
Exploration (Beijing) ; 2(5): 20220010, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37325504

RESUMO

Chemically manipulating bacterial surface structures, a cutting-edge research direction in the biomedical field, predominantly relies on metabolic labeling by now. However, this method may involve daunting precursor synthesis and only labels nascent surface structures. Here, we report a facile and rapid modification strategy based on a tyrosinase-catalyzed oxidative coupling reaction (TyOCR) for bacterial surface engineering. This strategy employs phenol-tagged small molecules and tyrosinase to initiate direct chemical modification of Gram-positive bacterial cell walls with high labeling efficiency, while Gram-negative bacteria are inert to this modification due to the hindrance of an outer membrane. By using the biotin‒avidin system, we further present the selective deposition of various materials, including photosensitizer, magnetic nanoparticle, and horseradish peroxidase, on Gram-positive bacterial surfaces, and realize the purification/isolation/enrichment and naked-eye detection of bacterial strains. This work demonstrates that TyOCR is a promising strategy for engineering live bacterial cells.

14.
Front Psychol ; 13: 1023945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36710850

RESUMO

Effective supervision is one of the important ways to ensure the smooth implementation of Public-Private Partnership (PPP) projects. To understand the characteristics of the decision-making behavior of the public and private sectors in the supervision of PPP projects and the influencing mechanisms of some factors, we combine prospect theory and mental accounting theory into the evolutionary game analysis. First, we use prospect theory to reflect the behavioral characteristics of game players when making decisions and classify the value function into a valence account and a cost account according to the mental accounting theory. Accordingly, we construct a payoff matrix based on prospect theory and mental accounting theory, and the system's equilibrium state is analyzed. Then, based on numerical simulations, the influence of different parameters on the behavior of the public and private sectors is analyzed, and management suggestions for practical reference are put forward based on the simulation results. The results show that the greater the perceived cost of active behavior for the public and private sectors, the less likely they will take active behavior. Secondly, there is insufficient incentive for the private sector to fulfill contracts when the penalties for its opportunistic behavior are minor. Thirdly, increasing the cost reference points and decreasing the valence reference points will promote the public and private sectors to adopt active behavior. Fourth, the public sector and the private sector are more inclined to take active behavior when they need to bear more significant risk losses. This study provides new ideas for the analysis of the game players' decision-making behaviors in the supervision of PPP projects and delivers a decision-making reference for reasonable supervision.

15.
Psicol. reflex. crit ; 35: 16, 2022. tab
Artigo em Inglês | LILACS, Index Psicologia - Periódicos | ID: biblio-1387031

RESUMO

Character strengths could efectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10­12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r = −0.14 to −0.3, p < 0.05 Bonferroni corrected). Character strengths explained a signifcant proportion of additional variance (14­22%) in fve types of behavior problems after controlling the efect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specifc character strengths showed an independent contribution (ß = −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership; ß = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character trengths were protective factors against behavior problems in early adolescents.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Estudantes/psicologia , Caráter , Comportamento do Adolescente , Comportamento Problema/psicologia , China
16.
ACS Omega ; 6(50): 34700-34711, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34963953

RESUMO

Gas injection and water injection are common and effective methods to improve oil recovery. To ensure its production effect, it is necessary to simulate the oilfield production process. However, traditional composition simulation runs a large number of calculations and takes a long time. Through the analysis of relevant data, we found that production is affected by many factors and has a strong sequential character. Therefore, this paper proposes a deep learning model for reservoir production prediction based on stacked long short-term memory network (LSTM). It is applied to other well patterns with a short production time and a few samples in the same oilfield block by transfer learning. The model achieves an effective combination with the actual reservoir production process. At the same time, it uses the knowledge learned from the well pattern with sufficient historical data to assist in the establishment of the model of the well pattern with limited data. This can obtain accurate prediction results and save the model training time, thus getting more effective application effects than composition simulation. This paper verifies the effectiveness of the proposed method through the data and multiple different injection combinations of the Tarim oilfield.

17.
Endocr Relat Cancer ; 28(12): 757-772, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34658364

RESUMO

Despite a general role for the HIF hydroxylase system in cellular oxygen sensing and tumour hypoxia, cancer-associated mutations of genes in this pathway, including PHD2, PHD1, EPAS1 (encoding HIF-2α) are highly tissue-restricted, being observed in pseudohypoxic pheochromocytoma and paraganglioma (PPGL) but rarely, if ever, in other tumours. In an effort to understand that paradox and gain insights into the pathogenesis of pseudohypoxic PPGL, we constructed mice in which the principal HIF prolyl hydroxylase, Phd2, is inactivated in the adrenal medulla using TH-restricted Cre recombinase. Investigation of these animals revealed a gene expression pattern closely mimicking that of pseudohypoxic PPGL. Spatially resolved analyses demonstrated a binary distribution of two contrasting patterns of gene expression among adrenal medullary cells. Phd2 inactivation resulted in a marked shift in this distribution towards a Pnmt-/Hif-2α+/Rgs5+ population. This was associated with morphological abnormalities of adrenal development, including ectopic TH+ cells within the adrenal cortex and external to the adrenal gland. These changes were ablated by combined inactivation of Phd2 with Hif-2α, but not Hif-1α. However, they could not be reproduced by inactivation of Phd2 in adult life, suggesting that they arise from dysregulation of this pathway during adrenal development. Together with the clinical observation that pseudohypoxic PPGL manifests remarkably high heritability, our findings suggest that this type of tumour likely arises from dysregulation of a tissue-restricted action of the PHD2/HIF-2α pathway affecting adrenal development in early life and provides a model for the study of the relevant processes.


Assuntos
Neoplasias das Glândulas Suprarrenais , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Camundongos , Paraganglioma/genética , Feocromocitoma/genética
18.
ACS Nano ; 15(5): 8039-8068, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33974797

RESUMO

Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure-property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.


Assuntos
Glutationa , Neoplasias , Morte Celular , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico
19.
Clin Psychol Psychother ; 28(6): 1525-1534, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33780079

RESUMO

Both elevated intolerance of uncertainty (IU) and maladaptive metacognitive beliefs (MBs) were associated with depression. However, the relationship between MBs and IU in clinical depression is unclear. The current study aimed to investigate the putative impairment of MBs and IU in major depressive disorder (MDD) and explore the relationship between these two factors with depressive symptoms. Metacognition Questionnaire-30 Items (MCQ-30), Intolerance of Uncertainty Scale-Short Form (IUS-12) and clinical rating scales were administered to 53 patients with MDD and 56 healthy controls (HCs). Stepwise regressions were performed to explore independent contributions of MBs and IU on depression. Mediation analysis was used to examine associations among variables. Patients with MDD reported higher IUS-12 and MCQ-30 scores than HCs. Stepwise regressions revealed a unique contribution of negative MBs concerning the consequences of not controlling thoughts (MCQ-NC) on depression symptoms while controlling the effects of age, gender, anxiety symptoms and IU. MCQ-NC and negative MBs concerning the uncontrollability and danger of negative thinking (MCQ-NEG) completely mediated the effects of IU on depression and anxiety symptoms. Our results provided clear evidence that maladaptive negative MBs are directly associated with depression symptoms, and mediated the effect of IU on depression and anxiety symptoms, suggesting that IU and MBs influence clinical symptoms in a hierarchical manner.


Assuntos
Transtorno Depressivo Maior , Metacognição , Ansiedade , Depressão , Transtorno Depressivo Maior/complicações , Humanos , Inquéritos e Questionários , Incerteza
20.
Langmuir ; 36(39): 11637-11644, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32902987

RESUMO

Many noble metal-based nanoparticles have emerged for applications in cancer radiotherapy in recent years, but few investigations have been carried out for palladium nanoparticles. Herein, palladium nanosheets (Pd NSs), which possess a sheetlike morphology with a diameter of ∼14 nm and a thickness of ∼2 nm, were utilized as a sensitizer to improve the performance of radiotherapy. It was found that Pd NSs alone did not decrease the cell viability after treatment for as long as 130 h, suggesting the excellent cytocompatibility of the nanoagents. However, the viability of cancer cells treated with X-ray irradiation became lower, and the viability became even lower if the cells were co-treated with X-ray and Pd NSs, indicating the radiosensitization effect of Pd NSs. Additionally, compared with X-ray irradiation, the combined treatment of Pd NSs and X-ray irradiation induced the generation of more DNA double-stranded breaks and reactive oxygen species within cancer cells, which eventually caused elevated cell apoptosis. Moreover, in vivo experiments also verified the radiosensitization effect and the favorable biocompatibility of Pd NSs, indicating their potential for acquiring satisfactory in vivo radiotherapeutic effect at lower X-ray doses. It is believed that the present research will open new avenues for the application of noble metal-based nanoparticles in radiosensitization.


Assuntos
Nanopartículas Metálicas , Radiossensibilizantes , Apoptose , Sobrevivência Celular , Nanopartículas Metálicas/toxicidade , Paládio , Radiossensibilizantes/toxicidade
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