Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
1.
J Mater Chem B ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585715

RESUMO

Gd(III) chelates are important T1-weighted contrast agents used in clinical magnetic resonance imaging (MRI), but their low longitudinal relaxivity (r1) results in limited imaging efficiency. In this study, we utilize a geometric confinement strategy to restrict a Gd chelate (Gd-DTPA) within the channels of a porous metal-organic framework material (MOF-808) for increasing its r1 relaxivity. Moreover, the Gd-DTPA-grafted MOF-808 nanoparticles were further surface modified with polyaniline (PANI) to construct an MRI-guided photothermal therapy platform. The resulting Gd-DTPA-MOF-808@PANI shows a high r1 relaxivity of 30.1 mM-1 s-1 (0.5 T), which is 5.4 times higher than that of the commercial contrast agent Magnevist. In vivo experiments revealed that Gd-DTPA-MOF-808@PANI has good T1-weighted contrast performance and can effectively guide photothermal ablation of tumors upon 808 nm laser irradiation. This work may shed some light on the design and preparation of high relaxation rate Gd-based contrast agents for theranostic application via utilization of versatile MOF materials.

2.
J Mater Chem B ; 9(37): 7734-7740, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586149

RESUMO

Superparamagnetic iron oxide nanoparticles with high magnetization strength and good biological safety have been widely used as magnetic resonance imaging (MRI) contrast agents for tumors. However, the accuracy of tumor diagnosis is still low due to the lack of tumor targeting and the interference signals from normal tissues. Endogenous substances in tumor (such as high levels of GSH and pH) stimuli-responsive contrast agents could offer higher sensitivity for tumor diagnosis. Herein, based on the characteristic of overexpression of GSH in tumors, we propose an ultra-small Fe3O4 assembly as an endogenous GSH responsive MRI contrast agent. The ultra-small superparamagnetic Fe3O4 are bonded to the crosslinker cystamine to synthesize Fe3O4 nanoclusters, which exhibit a T2 imaging effect. When the contrast agent reaches the tumor tissue, the disulfide bond in cystamine is induced by GSH to break, the Fe3O4 nanoclusters are disassembled into ultra-small Fe3O4 nanoparticles, and the relaxation signal changes from T2 to T1, which is helpful for accurate diagnosis of tumors. In vivo experiments have shown that Fe3O4 nanoclusters can rapidly respond to overexpressed GSH in tumor sites for T2/T1 switchable imaging. This work not only designed an endogenous GSH responsive platform through simple synthesis methods, but also improved the accuracy of tumor diagnosis through the transformation of T2/T1 MRI signals.

3.
ACS Appl Mater Interfaces ; 13(33): 39100-39111, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382406

RESUMO

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H2O2) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H2O2 in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.


Assuntos
Antineoplásicos/química , Monóxido de Carbono/química , Compostos de Ferro/química , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/metabolismo , Nanopartículas Metálicas/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de Medicamentos , Feminino , Glutationa/química , Humanos , Peróxido de Hidrogênio/química , Imunoterapia/métodos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Neoplasias Experimentais , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
4.
Cancer Med ; 10(19): 6687-6696, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34382376

RESUMO

PURPOSE: The optimal practice regarding cervical lymph node biopsy (CLNB) remains to be defined to provide the best clinical management in nasopharyngeal carcinoma (NPC). This study aimed to investigate the effect of CLNB on the survival of NPC patients. METHODS: Patients diagnosed with NPC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression, Kaplan-Meier method, Cox proportional hazards regression analysis, and propensity score matching (PSM) were used to determine the factors associated with CLNB and prognostic effect of CLNB of NPC. RESULTS: We included 1903 patients in this study. There were 321 (16.9%) and 1582 (83.1%) patients with and without CLNB, respectively. The percentage of CLNB was 19.4% in 2004 and was decreased to 8.6% in 2015 (p = 0.044). Patients diagnosed in later years (p = 0.008), older age (p < 0.001), Chinese (p = 0.002), advanced tumor stage (p < 0.001), and early nodal stage (p = 0.003) were less likely to receive additional CLNB. In patients who received additional CLNB, the 5-years NPC-specific survival (NPCSS) was 83.6%, which was similar to patients without CLNB (80.1%, p = 0.159). In addition, a similar 5-years NPCSS was found between those receiving biopsy or aspiration of regional lymph node and those receiving lymph node resection (p = 0.584). There were 187 pairs of patients who were completely matched using PSM, the multivariate prognostic analyses indicated that the receipt of CLNB was not associated with an inferior outcome in the PSM cohort (p = 0.349). Similar results were found after stratification by the year of diagnosis, race/ethnicity, and histology. CONCLUSION: Additional CLNB is not associated with an inferior survival outcome in NPC. Our study provides a reference for the clinical practice of NPC.

5.
Bioinformatics ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273146

RESUMO

MOTIVATION: To complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human-virus protein-protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving prediction performance. RESULTS: To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron. Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two transfer learning methods (i.e., 'frozen' type and 'fine-tuning' type) that reliably predict interactions in a target human-virus domain based on training in a source human-virus domain, by retraining CNN layers. Finally, we utilize the 'frozen' type transfer learning approach to predict human-SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
Mater Sci Eng C Mater Biol Appl ; 126: 112157, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082962

RESUMO

Curcumin is a kind of anti-cancer chemotherapeutic drug and has been demonstrated to be able to produce reactive oxygen species (ROS) under the stimuli of ultrasound (US). Herein, gadolinium-doped hollow mesoporous silica nanospheres (Gd-HMSNs) loaded with curcumin (Cur) and conjugated with carboxymethyl dextran (CMD) have been facilely fabricated and applied for magnetic resonance imaging (MRI)-guided synergistic cancer sonodynamic-chemotherapy. The as-prepared multifunctional theranostic nanoplatform (Cur@Gd-HMSNs-CMD) shows high drug loading capacity, satisfactory biocompatibility, pH-responsive degradation, and US-triggered drug release. Due to the release of Gd3+ ions or oligomers during degradation, the nanoplatform Cur@Gd-HMSNs-CMD could serve as an effective contrast agent for T1-weighted MRI to guide cancer treatment. More significantly, in vivo experiments show that the Cur@Gd-HMSNs-CMD can efficiently inhibit the tumor growth by a high inhibition rate of ~85.6% under US irradiation, mainly resulting from the synergistic effect of sonodynamic-chemotherapy. This innovative "two-in-one" theranostic nanoplatform using a single drug provides a new strategy for developing "all-in-one" nanomaterials for combined cancer treatment.


Assuntos
Curcumina , Nanopartículas , Nanosferas , Neoplasias , Curcumina/farmacologia , Gadolínio , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Dióxido de Silício , Nanomedicina Teranóstica
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 917-923, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105494

RESUMO

OBJECTIVE: To explore the distribution characteristics of main antigen gene frequencies of Duffy,Diego,Kidd,Dombrock,MNS,Lutheran,Kell,Colton,Scianna,Yt,Knops and Indian in red blood cell blood group system of Li nationality in Hainan Province. METHODS: Antigens in twelve rare blood group systems of 214 Li people in Hainan Province were genotyped and analyzed by polymerase chain reaction-sequence specific primers (PCR-SSP). RESULTS: The gene frequency of antigens in twelve rare blood group systems of 214 Li people in Hainan Province including: the gene frequency of Duffy blood group system: fya=0.9556,fyb=0.0444;the gene frequency of Diego blood group system: Dia=0.0678,Dib=0.9322;the gene frequency of Kidd blood group system:JKa=0.4533,JKb=0.5467;the gene frequency of Dombrock blood group system:DOa=0.1051,DOb=0.8949;the gene frequency of MNS blood group system:M=0.8131,N=0.1869,S=0.0327,s=0.9673,Mur+=0.5748,Mur-=0.4252;the gene frequency of Lutheran blood group system:AUa=0.8318,AUb=0.1682;the Kell, Colton, Scianna, Yt, Knops and Indian blood type systems showed a monomorph and the genotype was kk, coacoa, Sc1Sc1, YtaYta, KnaKna and InbInb. The observed and expected genotype values in twelve rare blood group systems of Li nationality in Hainan province were obeyed by the Hardy-Weinberg genitic rules. The difference between the observed and expectated values of the Kidd blood group system showed significant differences(χ2=17.1946,P=0.0002). CONCLUSION: The genetic distribution and genetic status in twelve rare blood group systems of Li nationality in Hainan Province are relatively stable. The gene distribution of Duffy, Diego, Kidd, Drombrock, MNS and Lutheran blood group systems are polymorphic and show unique distribution characteristics compared with other regions and different nationalities. The gene frequency distribution of Kell、Colton、Scianna、Yt、Knops、Indian blood group systems are monomorphic.


Assuntos
Antígenos de Grupos Sanguíneos , Grupos Étnicos , Antígenos de Grupos Sanguíneos/genética , Frequência do Gene , Genótipo , Humanos , Sistema do Grupo Sanguíneo Kidd , Polimorfismo Genético
8.
J Mater Chem B ; 9(20): 4241-4248, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34008693

RESUMO

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Monóxido de Carbono/química , Complexos de Coordenação/farmacologia , Sistemas de Liberação de Medicamentos , Mitocôndrias/efeitos dos fármacos , Fotoquimioterapia , Oxigênio Singlete/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Raios Infravermelhos , Mitocôndrias/metabolismo , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas
9.
J Mater Chem B ; 9(15): 3401-3411, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881445

RESUMO

Hydroxyapatite (HA) has attracted wide attention for medical application due to its biocompatibility and bioactivity. However, the infection problems of HA remain among the leading reasons for implantation failure. Thus, it is urgent to endow HA biomaterials with antibacterial activity. Herein, the high antibacterial activity was achieved by introducing trace Mn3+ and H vacancy couples in HA through a facile heat-treatment strategy in air. The theoretical results indicated that Mn3+ was preferentially substituted for the Ca(2) site in the HA structure with a charge-compensating H vacancy appearing at the adjacent OH- site. The antibacterial tests showed that Mn-HA possessed antibacterial activity towards both E. coli and S. aureus with trace Mn content at the ppm level, and implied that Mn3+ and centers may play an important role in the antibacterial process. The Mn3+ and couples in Mn-HA, serving as oxidative and reductive centers respectively, could then collectively participate in the CoQ/CoQH2 redox cycling and synergistically facilitate the accumulation of CoQ˙- and ROS radicals. This enhanced ROS production was the main factor to endow Mn-HA with efficient antibacterial activity. Moreover, the in vitro bioactivity assay showed that Mn-HA materials exhibited enhanced osteogenic activity and good biocompatibility. Therefore, this work not only provides a feasible method to control the oxidation state of Mn elements in HA, but also proposes a novel trace Mn3+-doped HA for potential applications in tissue engineering.


Assuntos
Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/farmacologia , Escherichia coli/efeitos dos fármacos , Manganês/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Durapatita/síntese química , Durapatita/química , Manganês/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula
10.
Brief Bioinform ; 22(5)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-33693490

RESUMO

The protein-protein interactions (PPIs) between human and viruses mediate viral infection and host immunity processes. Therefore, the study of human-virus PPIs can help us understand the principles of human-virus relationships and can thus guide the development of highly effective drugs to break the transmission of viral infectious diseases. Recent years have witnessed the rapid accumulation of experimentally identified human-virus PPI data, which provides an unprecedented opportunity for bioinformatics studies revolving around human-virus PPIs. In this article, we provide a comprehensive overview of computational studies on human-virus PPIs, especially focusing on the method development for human-virus PPI predictions. We briefly introduce the experimental detection methods and existing database resources of human-virus PPIs, and then discuss the research progress in the development of computational prediction methods. In particular, we elaborate the machine learning-based prediction methods and highlight the need to embrace state-of-the-art deep-learning algorithms and new feature engineering techniques (e.g. the protein embedding technique derived from natural language processing). To further advance the understanding in this research topic, we also outline the practical applications of the human-virus interactome in fundamental biological discovery and new antiviral therapy development.

11.
Plant Cell ; 33(6): 2058-2071, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-33730156

RESUMO

Drought poses a major environmental threat to maize (Zea mays) production worldwide. Since maize is a monoecious plant, maize grain yield is dependent on the synchronous development of male and female inflorescences. When a drought episode occurs during flowering, however, an asynchronism occurs in the anthesis and silking interval (ASI) that results in significant yield losses. The underlying mechanism responsible for this asynchronism is still unclear. Here, we obtained a comprehensive development-drought transcriptome atlas of maize ears. Genes that function in cell expansion and growth were highly repressed by drought in 50 mm ears. Notably, an association study using a natural-variation population of maize revealed a significant relationship between the level of α-expansin4 (ZmEXPA4) expression and drought-induced increases in ASI. Furthermore, genetic manipulation of ZmEXPA4 expression using a drought-inducible promoter in developing maize ears reduced the ASI under drought conditions. These findings provide important insights into the molecular mechanism underlying the increase in ASI in maize ears subjected to drought and provide a promising strategy that can be used for trait improvement.

12.
Cancer Med ; 10(5): 1634-1643, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33586323

RESUMO

BACKGROUND: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. METHODS: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. RESULTS: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis. CONCLUSIONS: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia/mortalidade , Mastectomia/estatística & dados numéricos , Mastectomia Segmentar/mortalidade , Mastectomia Segmentar/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/mortalidade , Radioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Programa de SEER , Adulto Jovem
13.
J Mater Chem B ; 9(7): 1787-1791, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33595044

RESUMO

Iron-based coordination complexes are showing increasing potential to be alternatives for T1-weighted magnetic resonance imaging (MRI) and contribute to the safety of gadolinium-based compounds. In this work, three water-soluble iron-based complexes constructed using catechol ligands exhibiting T1-weighted MRI contrast behavior are described. The longitudinal relaxivity (r1) increase from 0.88 to 1.43 mM-1 s-1 mainly depends on the sizes and the number of water molecules in the second and outer spheres around the discrete complexes.


Assuntos
Materiais Biocompatíveis/química , Meios de Contraste/química , Compostos Férricos/química , Imageamento por Ressonância Magnética , Animais , Linhagem Celular , Humanos , Camundongos , Estrutura Molecular , Tamanho da Partícula , Solubilidade , Propriedades de Superfície , Água/química
14.
Future Oncol ; 17(17): 2183-2192, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33605163

RESUMO

Aim: To investigate the benefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scores of 26-30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patients received adjuvant chemotherapy. Patients with higher tumor grade, larger tumors and younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patients without chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated or undifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26-30, especially for patients with high-grade tumors.

15.
Brief Bioinform ; 22(2): 832-844, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33515030

RESUMO

While leading to millions of people's deaths every year the treatment of viral infectious diseases remains a huge public health challenge.Therefore, an in-depth understanding of human-virus protein-protein interactions (PPIs) as the molecular interface between a virus and its host cell is of paramount importance to obtain new insights into the pathogenesis of viral infections and development of antiviral therapeutic treatments. However, current human-virus PPI database resources are incomplete, lack annotation and usually do not provide the opportunity to computationally predict human-virus PPIs. Here, we present the Human-Virus Interaction DataBase (HVIDB, http://zzdlab.com/hvidb/) that provides comprehensively annotated human-virus PPI data as well as seamlessly integrates online PPI prediction tools. Currently, HVIDB highlights 48 643 experimentally verified human-virus PPIs covering 35 virus families, 6633 virally targeted host complexes, 3572 host dependency/restriction factors as well as 911 experimentally verified/predicted 3D complex structures of human-virus PPIs. Furthermore, our database resource provides tissue-specific expression profiles of 6790 human genes that are targeted by viruses and 129 Gene Expression Omnibus series of differentially expressed genes post-viral infections. Based on these multifaceted and annotated data, our database allows the users to easily obtain reliable information about PPIs of various human viruses and conduct an in-depth analysis of their inherent biological significance. In particular, HVIDB also integrates well-performing machine learning models to predict interactions between the human host and viral proteins that are based on (i) sequence embedding techniques, (ii) interolog mapping and (iii) domain-domain interaction inference. We anticipate that HVIDB will serve as a one-stop knowledge base to further guide hypothesis-driven experimental efforts to investigate human-virus relationships.

16.
J Inorg Biochem ; 216: 111354, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33454609

RESUMO

Multifunctional drugs with synergistic effects have been widely developed to enhance the treatment efficiency of various diseases, such as malignant tumors. Herein, a novel bifunctional manganese(I)-based prodrug [MnBr(CO)3(APIPB)] (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl)benzamide) with inhibitory histone deacetylase (HDAC) activity and light-controlled carbon monoxide (CO) delivery was successfully designed and synthesized. [MnBr(CO)3(APIPB)] readily released CO under visible light irradiation (λ > 400 nm) through which the amount of released CO could be controlled by manipulating light power density and illumination time. In the absence of light irradiation, the cytotoxic effect of [MnBr(CO)3(APIPB)] on cancer cells was greater than that of the commercially available HDAC inhibitor MS-275. Consequently, with a combination of CO delivery and HDAC inhibitory activity, [MnBr(CO)3(APIPB)] showed a remarkably enhanced antitumor effect on HeLa cells (IC50 = 3.2 µM) under visible light irradiation. Therefore, this approach shows potential for the development of medicinal metal complexes for combined antitumor therapies.


Assuntos
Antineoplásicos , Monóxido de Carbono , Inibidores de Histona Desacetilases , Luz , Manganês , Neoplasias/tratamento farmacológico , Pró-Fármacos , Monóxido de Carbono/química , Monóxido de Carbono/farmacocinética , Monóxido de Carbono/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Complexos de Coordenação/farmacologia , Células HeLa , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacocinética , Inibidores de Histona Desacetilases/farmacologia , Humanos , Manganês/química , Manganês/farmacocinética , Manganês/farmacologia , Neoplasias/enzimologia , Neoplasias/patologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia
17.
Nanomedicine ; 32: 102335, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33220508

RESUMO

Targeted T1-T2 MRI contrast agents, which can eliminate the difficulty of image matching across multiple imaging instruments and permit specific localization of lesions, are promising candidates for more accurate diagnosis of tumors. In this study, ultrasmall Fe@Fe3O4 nanoparticles were designed and synthesized as T1-T2 dual-mode MRI contrast agents for accurate tumor imaging. First, to investigate the influence of nanoparticle size, Fe@Fe3O4 nanoparticles with diameters of 4, 8, and 12 nm were prepared, among which the 8 nm 3-(3,4-dihydroxyphenyl)propionic acid (DHCA)-modified nanoparticles exhibited the optimal T1-T2 dual-mode MRI performance. Next, to develop a tumor-targeted contrast agent, the DHCA-Fe@Fe3O4 nanoparticles were conjugated with the F56 peptide, which targets the vascular endothelial growth factor receptor, and the resulting F56-DHCA-Fe@Fe3O4 nanoparticles were found to exhibit good T1-T2 dual-mode imaging and tumor-targeting performance both in vitro and in vivo, indicating the nanoparticles represent a new research tool for accurate tumor diagnosis.

18.
Acta Biomater ; 121: 592-604, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33316398

RESUMO

The oxygen consumption-induced hypoxia and the high concentration of glutathione in tumor microenvironment limit the treatment outcomes of sonodynamic therapy (SDT). SDT needs to be combined with other treatment modalities to achieve the desired therapeutic efficiency. In this study, an oxidized g-C3N4 (OCN) nanosheet-based theranostic nanoplatform is developed for sonodynamic and nitric oxide (NO) combination therapy of cancer. The OCN nanosheets are successively modified with amino-terminated 6-armed polyethylene glycol, chlorin e6, and Gd3+ ions, and then the as-prepared OCN-PEG-(Ce6-Gd3+) nanosheets are loaded with the NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6). Upon ultrasound (US) irradiation, the OCN-PEG-(Ce6-Gd3+)/BNN6 nanocomposite can induce the generation of reactive oxygen species (ROS) and simultaneously release NO molecules to effectively kill the cancer cells, thereby significantly suppressing the tumor growth. Moreover, a good in vivo T1-weighted magnetic resonance imaging (MRI) contrast effect is achieved after intravenous injection of OCN-PEG-(Ce6-Gd3+)/BNN6 due to remarkably enhanced contrast performance of the nanocomposite. Therefore, the OCN-PEG-(Ce6-Gd3+)/BNN6 formulation can serve as a promising theranostic agent for MRI-guided sonodynamic-NO combination therapy.


Assuntos
Óxido Nítrico , Polietilenoglicóis , Linhagem Celular Tumoral , Imageamento por Ressonância Magnética , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica
19.
Sci Rep ; 10(1): 22070, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328559

RESUMO

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Invasividade Neoplásica , Fatores de Risco , Taxa de Sobrevida
20.
mSystems ; 5(6)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144314

RESUMO

Human immunodeficiency virus type 1 (HIV-1) depends on a class of host proteins called host dependency factors (HDFs) to facilitate its infection. So far experimental efforts have detected a certain number of HDFs, but the gene inventory of HIV-1 HDFs remains incomplete. Here, we implemented an existing network-based gene discovery strategy to predict HIV-1 HDFs. First, an encoding scheme based on a publicly available human tissue-specific gene functional network (GIANT; http://giant.princeton.edu/) was designed to convert each human gene into a 25,825-dimensional feature vector. Then, a random forest-based predictive model was trained on a data set containing 868 known HDFs and 1,736 non-HDFs. Through 5-fold cross-validation, an independent test, and comparison with one existing method, the proposed prediction method consistently revealed accurate and competitive performance. The highlight of our method should be ascribed to the introduction of the GIANT encoding scheme, which contains rich information regarding gene interactions. By merging known HDFs and genome-wide HDF prediction results, network analysis was conducted to catch the common patterns of HDFs in the context of the GIANT network. Interestingly, HDFs reveal significantly lower betweenness than HIV-1-interacting human proteins (i.e., HIV targets). In the meantime, the functional roles of HDFs were also examined by mapping all the HDF candidates into human protein complexes. Especially, we observed the frequent co-occurrence of HDFs and HIV targets at the protein complex level. Collectively, we hope the proposed prediction method not only can accelerate the HDF identification and antiviral drug target discovery, but also can provide some mechanistic insights into human-virus relationships.IMPORTANCE Identification of HIV-1 HDFs remains a crucial step to understand the complicated relationships between human and HIV-1. To complement the experimental identification of HDFs, we have implemented an existing network-based gene discovery strategy to predict HDFs from the human genome. The core idea of the proposed method is that the rich information deposited in host gene functional networks can be effectively utilized to infer the potential HDFs. We hope the proposed prediction method could further guide hypothesis-driven experimental efforts to interrogate human-HIV-1 relationships and provide new hints for the development of antiviral drugs to combat HIV-1 infection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...