Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 73
Filtrar
1.
Bipolar Disord ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606159

RESUMO

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < .002, z =-7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction of MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

2.
Angew Chem Int Ed Engl ; 60(48): 25365-25371, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34528355

RESUMO

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP). After systemic administration, the developed HAL/3BP@X-MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co-localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34119573

RESUMO

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

4.
Cell Prolif ; 54(4): e12989, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33609051

RESUMO

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.


Assuntos
Proteínas/metabolismo , Sarcopenia/patologia , Esteróis/metabolismo , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Calcifediol/metabolismo , China/epidemiologia , Exercício Físico , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sarcopenia/epidemiologia , Fatores Sexuais , Testosterona/análise
5.
J Affect Disord ; 284: 217-228, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33609956

RESUMO

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.


Assuntos
Transtorno Depressivo Maior , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Dominância Cerebral , Humanos , Imageamento por Ressonância Magnética
6.
Adv Mater ; 33(7): e2005562, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33432702

RESUMO

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported. M1 macrophage-derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5-trichloro-6-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox-EMCH). After administration, the as-prepared system actively targets tumor cells because of the tumor-homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H2 O2 . The reaction between H2 O2 and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen (1 O2 ) for photodynamic therapy (PDT). Meanwhile, 1 O2 -induced membrane rupture leads to the release of Dox-EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.


Assuntos
Antineoplásicos/química , Doxorrubicina/análogos & derivados , Portadores de Fármacos/química , Vesículas Extracelulares/química , Hidrazonas/química , Macrófagos/química , Oxalatos/química , Porfirinas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Humanos , Hidrazonas/farmacologia , Imunoterapia , Masculino , Camundongos , Oxalatos/farmacologia , Processos Fotoquímicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Oxigênio Singlete/metabolismo
7.
Biomed Mater ; 16(2): 022009, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33307545

RESUMO

Extracellular vesicles (EVs) are cell secretory native components with long-circulation, good biocompatibility, and physiologic barriers cross ability. EVs derived from different donor cells inherit varying characteristics and functions from their original cells and are favorable to serve as vectors for diagnosing and treating various diseases. However, EVs nanotheranostics are still in their infancy because of their limited accumulation at lesion sites and compromised therapy efficiency. Hence, engineering modification of EVs is usually needed to further enhance their stability, biological activity, and lesion-targeting capacity. Herein, we overview the characteristics of EVs from different sources, as well as the latest developments of surface engineering and cargo loading methods. We also focus especially on advances in EVs-based disease theranostics. At the end of the review, we predict the obstacles and prospects of the future clinical application of EVs.

8.
Onco Targets Ther ; 13: 10775-10783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122916

RESUMO

Background: Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value. Materials and Methods: The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan-Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model. Results: CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls (P < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage (P = 0.039) and distant metastasis (P = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels (P = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS. Conclusion: Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma.

9.
ACS Nano ; 14(8): 9917-9928, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32706236

RESUMO

Effective multimodality phototheranostics under deep-penetration laser excitation is highly desired for tumor medicine, which is still at a deadlock due to lack of versatile photosensitizers with absorption located in the long-wavelength region. Herein, we demonstrate a stable organic photosensitizer nanoparticle based on molecular engineering of benzo[c]thiophene (BT)-based photoactivated molecules with strong wavelength-tunable absorption in the near-infrared region. Via molecular design, the absorption and singlet oxygen generation of BT molecules would be reliably tuned. Importantly, the nanoparticles with a red-shifted absorption peak of 843 nm not only show over 10-fold reactive oxygen species yield compared with indocyanine green but also demonstrate a notable photothermal effect and photoacoustic signal upon 808 nm excitation. The in vitro and in vivo experiments substantiate good multimodal anticancer efficacy and imaging performance of BT theranostics. This work provides an organic photosensitizer nanoparticle with long-wavelength excitation and high photoenergy conversion efficiency for multimodality phototherapy.


Assuntos
Nanopartículas , Fármacos Fotossensibilizantes , Fototerapia , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica
10.
Biomaterials ; 250: 119963, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32334199

RESUMO

Atherosclerosis, as a silent killer, remains one of the most common causes of human morbidity and mortality worldwide due to the lack of efficient strategy for early detection and targeted therapy. In this work, a self-driven bioinspired nanovehicle is developed, which can accurately manage early atherosclerosis with simultaneously multiple-targeting, dual-modality therapy as well as noninvasive magnetic resonance imaging (MRI). The magnetic nanoclusters (MNCs) with satisfactory superparamagnetism are camouflaged with leukocyte membranes, thus acquiring inherently targeting and transmigrating capabilities to intimal foam cells in early atherosclerotic lesions, which is validated using tailor-made microfluidic devices and transwell assays. Upon sequentially embedding an anti-inflammatory drug simvastatin (ST) and decorating a targetable apolipoprotein A-I mimetic 4F peptide (AP), the as-fabricated MNC@M-ST/AP exhibits excellent anti-atherosclerotic effects by alleviating inflammation and oxidative stress as well as promoting cholesterol efflux via RCT pathways. This bioinspired leukocyte membrane-hitchhiking strategy will open new perspectives for the future clinical translations of biocompatible nanosystem in early detection and treatment of atherosclerosis.


Assuntos
Aterosclerose , Aterosclerose/diagnóstico por imagem , Aterosclerose/tratamento farmacológico , Humanos , Inflamação , Leucócitos , Peptídeos , Sinvastatina
11.
Biomater Sci ; 8(8): 2283-2288, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32163067

RESUMO

Highly efficient tumor-targeted therapy remains a great challenge due to the complexity and heterogeneity of tumor tissues. Herein, we developed an in vivo two-step tumor-targeting strategy by combining metabolic lipid-engineering with a stain-promoted azide-alkyne 1,3-dipolar cycloaddition (SPAAC) reaction, independent of the tumor microenvironment and cell phenotype. Firstly, exogenously-supplied azidoethyl-cholines (AECho) were metabolically incorporated into the cell membranes in tumor tissues through the intrinsic biosynthesis of phosphatidylcholine. The pre-inserted and accumulated azido groups (N3) could subsequently serve as 'artificial chemical receptors' for the specific anchoring of dibenzocyclooctyne (DBCO) modified biomimetic nanoparticles (DBCO-RBCG@ICG) via in situ click chemistry, resulting in significantly enhanced tumor-targeting and then an improved photothermal therapy effect. Such a two-step targeting strategy based on these cutting-edge techniques provided new insights into the universal and precise functionalization of living tissues for site-specific drug delivery in the diagnosis and treatment of various diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Membrana Eritrocítica , Animais , Linhagem Celular Tumoral , Colina/administração & dosagem , Colina/química , Química Click , Corantes/administração & dosagem , Corantes/química , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Lipídeos/administração & dosagem , Lipídeos/química , Engenharia Metabólica , Camundongos , Neoplasias/terapia , Fototerapia
12.
Acc Chem Res ; 53(1): 276-287, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31913016

RESUMO

During the past decade, there was a fast development of cell-based biomimetic systems, which are commonly derived from cell membranes, cell vesicles, or living cells. Such systems have unique and inherent bioinspired features originating from their parent biological systems. In particular, they are capable of (i) prolonging blood circulation time, (ii) avoiding immune response, (iii) targeting desired sites, (iv) providing antigens in cancer immunotherapy, and (v) loading and delivering therapeutic or imaging agents. Thus, these biomimetic systems are promising as prevention, detection, diagnosis, and therapeutic modalities. Though promising, these cell-based biomimetic systems are still far from wide application. One of the important reasons is the inevitable difficulty in their further efficient and precise functionalization. Bioorthogonal chemistry results in fast, specific, and high-yielding ligation under mild biological conditions without interactions with surrounding biomolecules or disturbance of the whole biosystem. Moreover, bioorthogonal chemical groups can be introduced into cells, especially into cell membranes, through cellular biosynthesis and metabolic incorporation. Hence, a specific and reliable approach for cell membrane functionalization based on bioorthogonal chemistry has been opportunely put forward and rapidly developed. In this Account, we summarize our recent research on the development of biomimetic systems by integrating bioorthogonal chemistry with biomimetic approaches. First, an exogenously supplied unnatural biosynthetic precursor (e.g., an amino acid or lipid) bearing a bioorthogonal group (e.g., azide or tetrazine) is fed to living cells and metabolically incorporated into targeted biomolecules via cellular biosynthesis regardless of the cell phenotype. After that, different functional molecules can be anchored to the cell membranes through bioorthogonal chemical reactions by using previously inserted "artificial chemical groups". Therefore, this safe, direct, and long-term engineering strategy endows the natural cell-based biomimetic systems with additional chemical or biological performances such as labeling, targeting, imaging, and therapeutic capabilities, providing a powerful tool for the construction of biomimetic systems. Interestingly, we have successfully fabricated various biomimetic systems and applied them in (1) living virus labeling, (2) targeting delivery and enrichment of drugs/imaging agents, and (3) disease theranostics. This Account may contribute to the further development of biomimetic systems and facilitate their biological and biomedical applications in the future. With this Account we also hope to attract more cooperative interests from different fields such as chemistry, materials science, biology, pharmacy, and medicine in promoting lab-to-clinic translation of cell-based biomimetic systems combined with these two cutting-edge techniques.


Assuntos
Materiais Biomiméticos/metabolismo , Membrana Celular/metabolismo , Animais , Materiais Biomiméticos/química , Membrana Celular/química , Humanos , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Vírus/química , Vírus/metabolismo
13.
Chem Rev ; 120(3): 1936-1979, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31951121

RESUMO

Uncovering the mechanisms of virus infection and assembly is crucial for preventing the spread of viruses and treating viral disease. The technique of single-virus tracking (SVT), also known as single-virus tracing, allows one to follow individual viruses at different parts of their life cycle and thereby provides dynamic insights into fundamental processes of viruses occurring in live cells. SVT is typically based on fluorescence imaging and reveals insights into previously unreported infection mechanisms. In this review article, we provide the readers a broad overview of the SVT technique. We first summarize recent advances in SVT, from the choice of fluorescent labels and labeling strategies to imaging implementation and analytical methodologies. We then describe representative applications in detail to elucidate how SVT serves as a valuable tool in virological research. Finally, we present our perspectives regarding the future possibilities and challenges of SVT.


Assuntos
Virologia/métodos , Viroses/virologia , Animais , Humanos , Fenômenos Fisiológicos Virais
14.
Angew Chem Int Ed Engl ; 59(5): 2018-2022, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31746532

RESUMO

Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano-bioconjugates for cancer therapy. Azide-modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne-modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH-sensitive linkers. After systemic administration, the nano-bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic-imine bonds of the nano-bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished "don't eat me" signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro-tumoral M2 to anti-tumoral M1.


Assuntos
Exossomos/metabolismo , Imunoterapia/métodos , Nanotecnologia/métodos , Neoplasias/terapia , Humanos , Neoplasias/patologia
15.
Angew Chem Int Ed Engl ; 59(10): 4068-4074, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31854064

RESUMO

Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation is a promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage-derived exosomes (M2 Exo) with inflammation-tropism and anti-inflammatory capabilities for AS imaging and therapy. M2 Exo are derived from M2 macrophages and further electroporated with FDA-approved hexyl 5-aminolevulinate hydrochloride (HAL). After systematic administration, the engineered M2 Exo exhibit excellent inflammation-tropism and anti-inflammation effects via the surface-bonded chemokine receptors and the anti-inflammatory cytokines released from the anti-inflammatory M2 macrophages. Moreover, the encapsulated HAL can undergo intrinsic biosynthesis and metabolism of heme to generate anti-inflammatory carbon monoxide and bilirubin, which further enhance the anti-inflammation effects and finally alleviate AS. Meanwhile, the intermediate protoporphyrin IX (PpIX) of the heme biosynthesis pathway permits the fluorescence imaging and tracking of AS.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aterosclerose/tratamento farmacológico , Heme/antagonistas & inibidores , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Tropismo/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Aterosclerose/metabolismo , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Heme/biossíntese , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout
16.
Chem Sci ; 11(8): 2155-2160, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34123305

RESUMO

Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate via responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation through the IEDDA reaction. The hierarchically regulated and locally confined Dox liberation led to dramatically decreased side-effects that were much lower than those of the clinical Doxorubicin Hydrochloride Liposomal Injection (Doxil), while the antitumor therapeutic effect was potent.

17.
Neuroimage Clin ; 28: 102514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33396001

RESUMO

BACKGROUND: Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. METHODS: The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. RESULTS: Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. CONCLUSIONS: Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.


Assuntos
Transtorno Depressivo Maior , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , China , Rede de Modo Padrão , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Neuroimagem
18.
Anal Chem ; 91(24): 15726-15731, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31729220

RESUMO

Improving the specific capture efficiency of CTCs, and meanwhile preventing the nonspecific adsorption of surrounding background cells, is the main focus of CTCs detection. Herein, a novel biomimetic microfluidic system was developed by combining the unique benefits of biomimetic nanoparticles and microfluidic techniques. The magnetic nanoclusters were camouflaged with leukocyte membrane fragments and decorated with aptamer SYL3C specific for EpCAM positive tumor cells and then loaded into the microfluidic chip with the help of magnets. By use of this system, more than 90% of the rare tumor cells in blood could be captured and detected within 20 min with almost no leukocyte background, indicating a great practical application potential for CTCs detection.


Assuntos
Biomimética/métodos , Neoplasias da Mama/patologia , Separação Celular/métodos , Microfluídica/métodos , Células Neoplásicas Circulantes/patologia , Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/metabolismo , Sobrevivência Celular , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Humanos , Magnetismo , Nanocompostos/química , Células Neoplásicas Circulantes/metabolismo , Células Tumorais Cultivadas
19.
Nano Lett ; 19(11): 8002-8009, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31626554

RESUMO

Oncolytic adenovirus (OA) is an ideal candidate for clinical anticancer treatment, because it can specifically replicate in tumor cells with high titer. However, its systemic administration is still hindered, because of severely compromised antitumor efficacy. Herein, an engineered OA was innovatively developed by enwrapping OA with calcium and manganese carbonates (MnCaCs) biomineral shell, which could protect the virus from removal of the host immune system and prolong its in vivo circulation. Upon accumulating in tumor sites, MnCaCs readily dissolved under the acidic microenvironment, releasing Mn2+ that could convert endogenous H2O2 into oxygen (O2) and then enhance the duplication ability of OA, thus significantly increased the antitumor efficacy. Meanwhile, Mn2+ and the increased O2 individually endowed the T1 modal magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) feasibility, providing real-time monitoring information for the therapy. This versatile engineered OA demonstrated its promise for visible and efficient oncolytic virotherapy by systemic administration.


Assuntos
Adenoviridae/química , Carbonato de Cálcio/química , Carbonatos/química , Manganês/química , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/química , Adenoviridae/genética , Animais , Engenharia Genética , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Vírus Oncolíticos/genética , Técnicas Fotoacústicas , Microambiente Tumoral
20.
Chem Sci ; 10(18): 4847-4853, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31183034

RESUMO

Although the antimonene (AM) nanomaterial is recently emerging as a new photothermal therapy (PTT) agent, its rapid degradation in physiological medium immensely limits its direct utilization. To this end, we herein engineered AM by the cooperation of dimension optimization, size control, and cell membrane (CM) camouflage. Compared with traditional AM nanosheets, the resulting AM nanoparticles (∼55 nm) cloaked with the CM (denoted as CmNPs) exhibited significantly improved stability and increased photothermal efficacy as well as superior tumor targeting capacity. After intravenous injection, the CmNPs enabled satisfactory photoacoustic/photothermal multimodal imaging at tumor sites. Meanwhile, the PTT together with the newly explored function of photodynamic therapy (PDT) achieved a potent combination therapy with few side effects. The maximized theranostic performance thus strongly recommends CmNPs as a safe and highly reliable modality for anticancer therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...