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1.
Nanomicro Lett ; 15(1): 216, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737506

RESUMO

Artificial cells are constructed from synthetic materials to imitate the biological functions of natural cells. By virtue of nanoengineering techniques, artificial cells with designed biomimetic functions provide alternatives to natural cells, showing vast potential for biomedical applications. Especially in cancer treatment, the deficiency of immunoactive macrophages results in tumor progression and immune resistance. To overcome the limitation, a BaSO4@ZIF-8/transferrin (TRF) nanomacrophage (NMΦ) is herein constructed as an alternative to immunoactive macrophages. Alike to natural immunoactive macrophages, NMΦ is stably retained in tumors through the specific affinity of TRF to tumor cells. Zn2+ as an "artificial cytokine" is then released from the ZIF-8 layer of NMΦ under tumor microenvironment. Similar as proinflammatory cytokines, Zn2+ can trigger cell anoikis to expose tumor antigens, which are selectively captured by the BaSO4 cavities. Therefore, the hierarchical nanostructure of NMΦs allows them to mediate immunogenic death of tumor cells and subsequent antigen capture for T cell activation to fabricate long-term antitumor immunity. As a proof-of-concept, the NMΦ mimics the biological functions of macrophage, including tumor residence, cytokine release, antigen capture and immune activation, which is hopeful to provide a paradigm for the design and biomedical applications of artificial cells.

2.
Plant Dis ; 107(7): 1979-1992, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36475741

RESUMO

Corynespora leaf spot, which is caused by Corynespora cassiicola (Berk. & M. A. Curtis) C.T. Wei (C. cassiicola), has been globally reported in many plant species. 'Hongyang' was reported as highly sensitive kiwifruit cultivar to C. cassiicola. This cultivar is an important germplasm resource in the Actinidiaceae family and is widely cultivated throughout China. Even though C. cassiicola has been identified as the pathogen associated with kiwifruits in China, the C. cassiicola population from kiwifruit has not been characterized based on morphology, phylogeny, and pathogenicity. In this study, 133 and 48 representative C. cassiicola isolates from kiwifruit and 11 other hosts, respectively, recovered from symptomatic leaves were classified into eight morphological subgroups based on host origins. Using three loci (rDNA ITS, caa5, and act1), a phylogenetic tree showed that C. cassiicola isolates in Sichuan Province were grouped into three clades. All kiwifruit isolates were genetically identical to the rubber isolates from different countries. However, most isolates from other hosts in this study were genetically identical to the cucumber, soybean, and cowpea isolates in China, Brazil, and the United States, and two strawberry isolates clustered with isolates from tomato and other hosts in China, Brazil, and the United States. Furthermore, we confirmed host shift of C. cassiicola among different plant species in this study. Although 51 isolates from kiwifruit and different hosts were pathogenic to kiwifruit, blueberry, cucumber, and soybean, virulence levels of the pathogen were diverse for four hosts. Kiwifruit isolates exhibited host specificity with regards to the original host in degree. In addition, those isolates revealed a correlation between morphology and pathogenicity. The results suggest that C. cassiicola in Sichuan Province were derived from three different phylogenetic lineages. Promotion of the susceptible 'Hongyang' cultivar led to the emergence of a regnant C. cassiicola population from kiwifruit. In conclusion, rapid development of the C. cassiicola-sensitive crop in agricultural systems led to the emergence of a regnant C. cassiicola population. In some dominant populations (e.g., the C. cassiicola population from kiwifruit in this study), host origin was found to be a key factor influencing the morphologic, genetic, and pathogenic characterization of C. cassiicola.


Assuntos
Ascomicetos , Cucumis sativus , Virulência , Filogenia , Doenças das Plantas/genética
3.
ACS Nano ; 16(12): 21491-21504, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36453617

RESUMO

Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temperature-dependent enzymatic kinetics. The safety window of cold temperatures (4-37 °C) for the human body is much wider than that of thermal temperatures (37-42 °C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temperature due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymatic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymatic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochemistry analysis and histological examination indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.


Assuntos
Temperatura Baixa , Neoplasias , Humanos , Temperatura , Nanomedicina , Catálise , Neoplasias/tratamento farmacológico
4.
Artigo em Inglês | MEDLINE | ID: mdl-37015635

RESUMO

We present experimental results to explore a form of bivariate glyphs for representing large-magnitude-range vectors. The glyphs meet two conditions: (1) two visual dimensions are separable; and (2) one of the two visual dimensions uses a categorical representation (e.g., a categorical colormap). We evaluate how much these two conditions determine the bivariate glyphs' effectiveness. The first experiment asks participants to perform three local tasks requiring reading no more than two glyphs. The second experiment scales up the search space in global tasks when participants must look at the entire scene of hundreds of vector glyphs to get an answer. Our results support that the first condition is necessary for local tasks when a few items are compared. But it is not enough for understanding a large amount of data. The second condition is necessary for perceiving global structures of examining very complex datasets. Participants' comments reveal that the categorical features in the bivariate glyphs trigger emergent optimal viewers' behaviors. This work contributes to perceptually accurate glyph representations for revealing patterns from large scientific results. We release source code, quantum physics data, training documents, participants' answers, and statistical analyses for reproducible science at https : //osf:io/4xcf5/?viewonly = 94123139df9c4ac984a1e0df811cd580.

5.
ACS Nano ; 15(8): 13188-13199, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34342966

RESUMO

Chemical messengers have been recognized as signaling molecules involved in regulating various physiological and metabolic activities. Nevertheless, they usually show limited regulatory efficiency due to the complexity of biological processes. Especially for tumor cells, antideath pathways and tumor metastasis are readily activated to resist chemical messenger regulation, further impairing antitumor outcomes. Therefore, it is imperative to develop strategies for tumor eradication with chemical messengers. Herein, a nanomessenger was prepared with signaling transduction cascades to amplify the regulatory activity of chemical messengers and mediate antitumor immunotherapy. Ca2+ and H2S as two chemical messengers were released from nanomessengers to synergistically elevate intracellular Ca2+ stress and mediate subsequent cell death. Meanwhile, zinc protoporphyrin (ZnPP) as a messenger amplifier suppressed the antideath effect of tumor cells. As a result, tumor cells underwent Ca2+-dependent cell death via signaling transduction cascades to release tumor-associated antigens, which further served as an in situ tumor vaccine to activate antitumor immunity. In vivo studies revealed that both primary tumors and distant metastases were markedly eradicated. Furthermore, immunological memory was fabricated to arrest tumor metastasis and recurrence. This work introduces cascade engineering into chemical messengers and thus offers a strategy for amplifying chemical messenger-mediated cellular regulation, which would promote the future development of chemical messenger-mediated immunotherapy.̀.


Assuntos
Imunoterapia , Neoplasias , Humanos , Transdução de Sinais , Neoplasias/terapia , Memória Imunológica , Morte Celular , Fatores Imunológicos
7.
Quant Imaging Med Surg ; 11(6): 2477-2485, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079717

RESUMO

BACKGROUND: Lymph node (LN) metastasis is the main prognostic factor for local recurrence and overall survival of patients with rectal cancer. The accurate evaluation of LN status in rectal cancer patients is associated with improved treatment and prognosis. This study aimed to apply deep transfer learning to classify LN status in patients with rectal cancer to improve N staging accuracy. METHODS: The study included 129 patients with 325 rectal cancer screenshots of LN T2-weighted (T2W) images from April 2018 to March 2019. Deep learning was applied through a pre-trained model, Inception-v3, for recognition and detection of LN status. The results were compared to manual identification by experienced radiologists. Two radiologists reviewed images and independently identified their status using various criteria with or without short axial (SA) diameter measurements. The accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were calculated. RESULTS: When the same radiologist performed the analysis, the AUC was not significantly different in the presence or absence of LN diameter measurements (P>0.05). In the deep transfer learning method, the PPV, NPV, sensitivity, and specificity were 95.2%, 95.3%, 95.3%, and 95.2%, respectively, and the AUC and accuracy were 0.994 and 95.7%, respectively. These results were all higher than that achieved with manual diagnosis by the radiologists. CONCLUSIONS: The internal details of LNs should be used as the main criteria for positive diagnosis when using MRI. Deep transfer learning can improve the MRI diagnosis of positive LN metastasis in patients with rectal cancer.

8.
J Proteomics ; 245: 104283, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34102345

RESUMO

Human milk is the first source of nutrition for infants, which delivers an array of unique bioactive components to offspring. Modern bovine-milk-based infant formulas are good substitutes when mother's milk is not available. As the third most abundant component in human milk, human free oligosaccharides (HMOs) may interference the analysis of total N-glycans on the glycoproteins in human milk. Herein, we combined acetone precipitation protein with the filter aided sample preparation method (FASP) to thoroughly remove HMOs and purify N-glycans. Furthermore, we also compared both N-glycosylation and glycoproteins between human and bovine milk, which may provide new ideas for the composition adjustment of infant formula in the food industry. SIGNIFICANCE: We described a new method, which can successfully remove HMOs, further extract and purify the N-glycans on glycoproteins from pooled human milk for MALDI-TOF MS analysis by applying acetone precipitation and FASP together. We applied the new method to purify the N-glycans from whey proteins in pooled bovine milk and compared the N-glycosylation differences between pooled human and bovine milk by MALDI-TOF MS. We first reported the difference of N-glycan pattern of glycoproteins between pooled bovine and human milk by lectin blotting, and found significant differences in types and abundance of glycoproteins between the two sourced milk.


Assuntos
Leite Humano , Leite , Animais , Bovinos , Glicoproteínas/metabolismo , Glicosilação , Humanos , Lactente , Leite/metabolismo , Leite Humano/metabolismo , Oligossacarídeos , Polissacarídeos
9.
Front Cardiovasc Med ; 8: 665993, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095256

RESUMO

Background: Exercise training has been extensively studied in heart failure (HF) and psychological disorders, which has been shown to worsen each other. However, our understanding of how exercise simultaneously protect heart and brain of HF patients is still in its infancy. The purpose of this study was to take advantage of big data techniques to explore hotspots and frontiers of mechanisms that protect the heart and brain simultaneously through exercise training. Methods: We studied the scientific publications on related research between January 1, 2003 to December 31, 2020 from the WoS Core Collection. Research hotspots were assessed through open-source software, CiteSpace, Pajek, and VOSviewer. Big data analysis and visualization were carried out using R, Cytoscape and Origin. Results: From 2003 to 2020, the study on HF, depression, and exercise simultaneously was the lowest of all research sequences (two-way ANOVAs, p < 0.0001). Its linear regression coefficient r was 0.7641. The result of hotspot analysis of related keyword-driven research showed that inflammation and stress (including oxidative stress) were the common mechanisms. Through the further analyses, we noted that inflammation, stress, oxidative stress, apoptosis, reactive oxygen species, cell death, and the mechanisms related to mitochondrial biogenesis/homeostasis, could be regarded as the primary mechanism targets to study the simultaneous intervention of exercise on the heart and brain of HF patients with depression. Conclusions: Our findings demonstrate the potential mechanism targets by which exercise interferes with both the heart and brain for HF patients with depression. We hope that they can boost the attention of other researchers and clinicians, and open up new avenues for designing more novel potential drugs to block heart-brain axis vicious circle.

10.
PLoS One ; 16(4): e0249280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793613

RESUMO

International scientific collaborations have always been regarded as critical actions to address global pandemics, however, there was an obvious uncertainty between international collaboration and the COVID-19 control. We aim to combine digital data-based strategies to produce meaningful and advanced insights into the imbalance between COVID-19 and international collaboration, as well as reveal possible influencing factors, and ultimately enhance global collaboration. We conducted three retrospective cohort studies using respectively COVID-19 data from WHO, a complete dataset of scientific publications on coronavirus-related research from WoS, and daily data from Google Trends (GT). The results of geovisualization and spatiotemporal analysis revealed that the global COVID19 pandemic still remains serious. The global issue of imbalance between international collaborations and pandemic does exit, and the nations with good pandemic control had their own characteristics in above-mentioned correlation. Digital epidemiology provides, at least in part, evidence-based assessment and scientific advice to understand the imbalance between international collaborations and COVID-19. Our investigation demonstrates that transdisciplinary conversation through digital data-based strategies can help us fully understand the complex factors influencing the effectiveness of international scientific collaboration, thus facilitating the global response to COVID-19.


Assuntos
Pesquisa Biomédica , COVID-19/epidemiologia , Gerenciamento de Dados , Cooperação Internacional , Pandemias/estatística & dados numéricos , Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/estatística & dados numéricos , Humanos , Colaboração Intersetorial , Estudos Retrospectivos
11.
Crit Rev Oncol Hematol ; 157: 103124, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33254041

RESUMO

The microRNA-26 family, including miR-26a, miR-26b, miR-1297 and miR-4465, is a group of broadly conserved small RNAs with identical sequences at the seed region. The expression of miR-26 could be induced by hypoxia via a HIF-dependent mechanism, and up-regulated during multiple cell differentiation. Accumulating studies have demonstrated that miR-26 family members could be detected in many different kinds of tumors, and their validated target genes are involved in cell metabolism, proliferation, differentiation, apoptosis, invasion and metastasis. The expression of miR-26 might be a potentially valuable biomarker and a new target for cancer therapy. In this review, miR-26 family and its target genes in tumorigenesis and development will be summarized as follows.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Humanos , MicroRNAs/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-32445660

RESUMO

Researchers have made considerable progress in elucidating psychological and exercise correlates of major depressive disorder (MDD). However, as the largest immune organ, far less is known about the role of gastrointestinal (GI) tract in the therapeutic mechanisms of exercise in MDD. In addition to the sites of the digestive tract that absorb nutrients, the GI tract also serves as a protective barrier against organisms. Inflammation and other consequences caused by disrupted GI barrier integrity are considered to be one of the mechanisms of depression, and the gut-brain axis (GBA) plays a critical role in this process. In this work, we observed the depression-like behaviors, intestinal barrier, central and peripheral inflammation, and related neurotransmitters through exercise intervention in the chronic unpredictable mild stress (CUMS) model, aiming to clarify the mechanisms of exercise to improve depression through GBA. Our results revealed that, following increased expressions of pro-inflammatory factors in intestine of CUMS mice, the levels of pro-inflammatory factors were all significantly raised in serum and brain simultaneously. Further, glial cells were activated in visceral nervous system and its related brain regions at the same time, accompanied by lower expression of occludin in CUMS mice. Importantly, our findings provide the first evidence that eight weeks of running exercise effectively inhibited neuro-immune interactions along gut-brain-axis and contributed obvious improvement of intestinal epithelial barrier (IEB). Finally, multivariate analysis putatively highlighted the role of exercise-induced IEB protection on depression treatment. We hope that our findings could warrant further study of therapeutic mechanisms of exercise in depression, specifically in disentangling the roles of intestinal function and IEB protection, and for developing more targeted clinical depression interventions.


Assuntos
Encéfalo/fisiopatologia , Depressão/psicologia , Depressão/terapia , Terapia por Exercício , Trato Gastrointestinal/fisiopatologia , Aerobiose , Animais , Ansiedade/psicologia , Depressão/fisiopatologia , Elevação dos Membros Posteriores , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Neurotransmissores , Estresse Psicológico/psicologia , Natação/psicologia
13.
FASEB J ; 34(6): 7330-7344, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32304342

RESUMO

Our understanding of the molecular mechanisms underlying adaptations to resistance exercise remains elusive despite the significant biological and clinical relevance. We developed a novel voluntary mouse weightlifting model, which elicits squat-like activities against adjustable load during feeding, to investigate the resistance exercise-induced contractile and metabolic adaptations. RNAseq analysis revealed that a single bout of weightlifting induced significant transcriptome responses of genes that function in posttranslational modification, metabolism, and muscle differentiation in recruited skeletal muscles, which were confirmed by increased expression of fibroblast growth factor-inducible 14 (Fn14), Down syndrome critical region 1 (Dscr1) and Nuclear receptor subfamily 4, group A, member 3 (Nr4a3) genes. Long-term (8 weeks) voluntary weightlifting training resulted in significantly increases of muscle mass, protein synthesis (puromycin incorporation in SUnSET assay) and mTOR pathway protein expression (raptor, 4e-bp-1, and p70S6K proteins) along with enhanced muscle power (specific torque and contraction speed), but not endurance capacity, mitochondrial biogenesis, and fiber type transformation. Importantly, weightlifting training profound improved whole-body glucose clearance and skeletal muscle insulin sensitivity along with enhanced autophagy (increased LC3 and LC3-II/I ratio, and decreased p62/Sqstm1). These data suggest that resistance training in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway.


Assuntos
Adaptação Fisiológica/fisiologia , Autofagia/fisiologia , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Condicionamento Físico Animal/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/fisiologia , Biogênese de Organelas , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
14.
Pathogens ; 9(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244886

RESUMO

Many species of the genus Bipolaris are important plant pathogens and often cause leaf spot, root rot, and seedling blight in an extremely wide range of hosts around the world. In recent years, maize leaf spot caused by Bipolaris species has frequently occurred with complex symptoms and is becoming increasingly serious in Sichuan Province of China. To investigate the population diversity of Bipolaris spp. and their corresponding symptoms in maize, 747 samples of maize leaf spot were collected from 132 sampling sites in 19 administrative districts of Sichuan Province from 2011 to 2018. Based on morphological characteristics, pathogenicity testing, and phylogenetic analysis of the rDNA internal transcribed spacer (ITS) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes, a total of 1186 Bipolaris isolates were identified as B. maydis, B. zeicola, B. cynodontis, B. oryzae, B. setariae, and B. saccharicola, among which B. maydis and B. zeicola were the dominant pathogenic species, accounting for 57.34% and 42.07% of the isolates, respectively. We found that B. zeicola isolates were mainly distributed in high altitude and cool mountainous areas, while B. maydis was more widely distributed in Sichuan Province. The typical symptoms caused by the Bipolaris species were clearly distinct in maize. The typical symptoms caused by B. maydis were elongated strip lesions, or fusiform, elliptical lesions, and those caused by B. zeicola were narrow linear lesions. Herein, B. saccharicola was first reported on maize and caused subrotund lesions. This study provides useful information for disease diagnosis and management for Bipolaris leaf spot in maize.

15.
Sci Rep ; 10(1): 6095, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269244

RESUMO

The common clinical symptoms of Friedreich's ataxia (FRDA) include ataxia, muscle weakness, type 2 diabetes and heart failure, which are caused by impaired mitochondrial function due to the loss of frataxin (FXN) expression. Endurance exercise is the most powerful intervention for promoting mitochondrial function; however, its impact on FRDA has not been studied. Here we found that mice with genetic knockout and knock-in of the Fxn gene (KIKO mice) developed exercise intolerance, glucose intolerance and moderate cardiac dysfunction at 6 months of age. These abnormalities were associated with impaired mitochondrial respiratory function concurrent with reduced iron regulatory protein 1 (Irp1) expression as well as increased oxidative stress, which were not due to loss of mitochondrial content and antioxidant enzyme expression. Importantly, long-term (4 months) voluntary running in KIKO mice starting at a young age (2 months) completely prevented the functional abnormalities along with restored Irp1 expression, improved mitochondrial function and reduced oxidative stress in skeletal muscle without restoring Fxn expression. We conclude that endurance exercise training prevents symptomatic onset of FRDA in mice associated with improved mitochondrial function and reduced oxidative stress. These preclinical findings may pave the way for clinical studies of the impact of endurance exercise in FRDA patients.


Assuntos
Ataxia de Friedreich/prevenção & controle , Condicionamento Físico Animal/métodos , Corrida , Animais , Ataxia de Friedreich/genética , Ataxia de Friedreich/fisiopatologia , Proteína 1 Reguladora do Ferro/genética , Proteína 1 Reguladora do Ferro/metabolismo , Proteínas de Ligação ao Ferro/genética , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Estresse Oxidativo , Frataxina
16.
Curr Med Chem ; 26(10): 1788-1805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28933294

RESUMO

Ascribe to the unique two-dimensional planar nanostructure with exceptional physical and chemical properties, black phosphorous (BP) as the emerging inorganic twodimensional nanomaterial with high biocompatibility and degradability has been becoming one of the most promising materials of great potentials in biomedicine. The exfoliated BP sheets possess ultra-high surface area available for valid bio-conjugation and molecular loading for chemotherapy. Utilizing the intrinsic near-infrared optical absorbance, BPbased photothermal therapy in vivo, photodynamic therapy and biomedical imaging has been realized, achieving unprecedented anti-tumor therapeutic efficacy in animal experiments. Additionally, the BP nanosheets can strongly react with oxygen and water, and finally degrade to non-toxic phosphate and phosphonate in the aqueous solution. This manuscript aimed to summarize the preliminary progresses on theranostic application of BP and its derivatives black phosphorus quantum dots (BPQDs), and discussed the prospects and the state-of-art unsolved critical issues of using BP-based material for theranostic applications.


Assuntos
Fósforo/uso terapêutico , Pontos Quânticos/uso terapêutico , Animais , Técnicas Biossensoriais/métodos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Portadores de Fármacos/uso terapêutico , Portadores de Fármacos/toxicidade , Humanos , Luz , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Imagem Óptica/métodos , Fósforo/química , Fósforo/efeitos da radiação , Fósforo/toxicidade , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Nanomedicina Teranóstica/métodos
17.
Nanoscale ; 10(39): 18795-18804, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30277241

RESUMO

Flake-shaped nanohybrids based on black phosphorus (BP) have been developed as multifunctional theranostic nanoplatforms for drug delivery, phototherapy and bioimaging. In this work, we report a facile strategy for fabrication of black phosphorus-Au nanoparticle hybrids (BP-AuNPs), which reveal an extraordinary near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity. The applications of the nanocomposites as therapeutic agents for high-performance chemo-photothermal tumor therapy are accomplished in vitro and in vivo. BP-AuNPs also exhibit wonderful surface-enhanced Raman scattering (SERS) activity under NIR laser excitation with a low Raman background, allowing BP-AuNPs to be used as a promising two-dimensional (2D) fingerprint nanoprobe for bio-SERS analysis. The cellular component identification and label-free live-cell bioimaging based on this type of 2D SERS substrate are generally investigated, which open up promising new perspectives in nanomedicine, including diagnosis, imaging and therapy.


Assuntos
Ouro , Nanopartículas Metálicas , Sondas Moleculares , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Animais , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Sondas Moleculares/química , Sondas Moleculares/farmacologia
18.
Molecules ; 22(12)2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29261144

RESUMO

Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment. Recently, the protein phosphatase 2A (PP2A) has been found to regulate the phosphorylation of some substrates involved in the relevant target of TNBC, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may be the effective therapeutic strategies or influence drug sensitivity to TNBCs. Furthermore, PP2A has also been found that could induce ER re-expression in ER-negative breast cancer cells, and which suggests PP2A could promote the sensitivity of tamoxifen to TNBCs as a resistance reversal agent. In this review, we will summarize the potential therapeutic value of PP2A as the main node in developing targeting agents, disrupting resistance or restoring drug sensitivity in TNBC.


Assuntos
Antineoplásicos/farmacologia , Proteína Fosfatase 2/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/enzimologia
19.
Sci Rep ; 7(1): 7894, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801668

RESUMO

Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7h&mKO). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles. Endurance exercise training partially reversed these abnormalities in skeletal muscle, but aggravated those in the heart also causing cardiac fibrosis, foetal gene reprogramming, and impaired mitochondrial biogenesis. Interestingly, exercise-trained Atg7h&mKO mice were better protected against obesity and insulin resistance with increased circulating fibroblast growth factor 21 (FGF21), elevated Fgf21 mRNA and protein solely in the heart, and upregulation of FGF21-target genes involved in thermogenesis and fatty acid oxidation in brown fat. These results indicate that autophagy is essential for the protective effects of exercise in the heart. However, the atypical remodelling elicited by exercise in the autophagy deficient cardiac muscle enhances whole-body metabolism, at least partially, via a heart-brown fat cross-talk involving FGF21.


Assuntos
Proteína 7 Relacionada à Autofagia/deficiência , Autofagia , Metabolismo Energético , Músculo Esquelético/patologia , Miocárdio/patologia , Condicionamento Físico Animal , Remodelação Ventricular , Animais , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Glucose/metabolismo , Resistência à Insulina , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Obesidade , Biogênese de Organelas
20.
ACS Appl Mater Interfaces ; 9(30): 25098-25106, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28671452

RESUMO

A multifunctional nanoplatform based on black phosphorus quantum dots (BPQDs) was developed for cancer bioimaging and combined photothermal therapy (PTT) and photodynamic therapy (PDT). BPQDs were functionalized with PEG chains to achieve improved biocompatibility and physiological stability. The as-prepared nanoparticles exhibite prominent near-infrared (NIR) photothermal and red-light-triggered photodynamic properties. The combined therapeutic application of PEGylated BPQDs were then performed in vitro and in vivo. The results demonstrate that the combined phototherapy significantly promote the therapeutic efficacy of cancer treatment in comparison with PTT or PDT alone. BPQDs could also serve as the loading platform for fluorescent molecules, allowing reliable imaging of cancer cells. In addition, the low cytotoxicity and negligible side effects to main organs were observed in toxicity experiments. The theranostic characteristics of PEGylated BPQDs provide an uplifting potential for the future clinical applications.


Assuntos
Pontos Quânticos , Fósforo , Fotoquimioterapia , Fototerapia , Nanomedicina Teranóstica
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