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1.
Front Oncol ; 10: 571167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304845

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.

2.
Biomater Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201168

RESUMO

The whole is a collection of parts and fulfills specific functions that the parts do not have. In this work, 50 nm Au NPs were in situ synthesized and close packed into a superorganism-like superstructure by means of microgel 3D networks. The combined microgel is endowed with ultra-wide absorption in visible and near-infrared regions between 500 and 1100 nm in spite of Au NPs not having this property. The strong collective plasmon coupling between neighboring Au NPs induces high photothermal conversion efficiency of the microgel system under irradiation at various laser wavelengths. Due to the good loading capability, microgels with nanocomposites can also load photosensitive drugs simultaneously and be used for combined cancer treatments of photothermal therapy and photodynamic therapy.

3.
Oncol Rep ; 44(1): 29-42, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32627007

RESUMO

Matrix metalloproteinases (MMPs) are involved in the cleavage of several components of the extracellular matrix and serve important roles in tumor growth, metastasis and invasion. Previous studies have focused on the expression of one or several MMPs in esophageal squamous cell carcinoma (ESCC); however, in the present study, the transcriptomics of all 23 MMPs were systematically investigated with a focus on the prognostic value of the combination of MMPs. In this study, 8 overlapping differentially expressed genes of the MMP family were identified based on data obtained from Gene Expression Omnibus and The Cancer Genome Atlas. The prognostic value of these MMPs were investigated; the receiver operating characteristic curves, survival curves and nomograms showed that the combination of 6 selected MMPs possessed a good predictive ability, which was more accurate than the prediction model based on Tumor­Node­Metastasis stage. Gene set enrichment analysis and gene co­expression analysis were performed to investigate the potential mechanism of action of MMPs in ESCC. The MMP family was associated with several signaling pathways, such as epithelial­mesenchymal transition (EMT), Notch, TGF­ß, mTOR and P53. Cell Counting Kit­8, colony formation, wound healing assays and western blotting were used to determine the effect of BB­94, a pan­MMP inhibitor, on proliferation and migration of ESCC cells. BB­94 treatment decreased ESCC cell growth, migration and EMT. Therefore, MMPs may serve both as diagnostic and prognostic biomarkers of ESCC, and MMP inhibition may be a promising preventive and therapeutic strategy for patients with ESCC.

4.
Microorganisms ; 8(5)2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32397545

RESUMO

Dickeya zeae is the causal agent of bacterial soft rot disease, with a wide range of hosts all over the world. At present, chemical agents, especially agricultural antibiotics, are commonly used in the prevention and control of bacterial soft rot, causing the emergence of resistant pathogens and therefore increasing the difficulty of disease prevention and control. This study aims to provide a safer and more effective biocontrol method for soft rot disease caused by D. zeae. The spot-on-lawn assay was used to screen antagonistic bacteria, and three strains including SC3, SC11 and 3-10 revealed strong antagonistic effects and were identified as Pseudomonas fluorescens, P. parafulva and Bacillus velezensis, respectively, using multi-locus sequence analysis (MLSA) based on the sequences of 16S rRNA and other housekeeping genes. In vitro antimicrobial activity showed that two Pseudomonas strains SC3 and SC11 were only antagonistic to some pathogenic bacteria, while strain 3-10 had broad-spectrum antimicrobial activity on both pathogenic bacteria and fungi. Evaluation of control efficacy in greenhouse trials showed that they all restrained the occurrence and development of soft rot disease caused by D. zeae MS2 or EC1. Among them, strain SC3 had the most impressive biocontrol efficacy on alleviating the soft rot symptoms on both monocotyledonous and dicotyledonous hosts, and strain 3-10 additionally reduced the occurrence of banana wilt disease caused by Fusarium oxysporum f. sp. cubensis. This is the first report of P. fluorescens, P. parafulva and B. velezensis as potential bio-reagents on controlling soft rot disease caused by D. zeae.

5.
ACS Appl Mater Interfaces ; 12(19): 21433-21440, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32319760

RESUMO

Dipeptide self-assembled hydrogels have potential biomedical applications because of their great biocompatibility, bioactivity, and tunable physicochemical properties, which can be modulated in the molecular level by design of amino acid sequences. Herein, a series of dipeptides (Fmoc-FL, -YL, -LL, and -YA) are designed to form shear-thinning hydrogels with self-healing and tunable mechanical properties by adjusting the synergetic effect of hydrophobic interactions (π-π stacking and hydrophobic effect) and hydrogen bonds of peptides through substitution of amino acid residues. The enhancement of hydrophobic interactions is a primary factor to promote mechanical rigidity of hydrogels, and strong hydrogen-bonding interactions between molecules contribute to the instantaneous self-healing property, which is supported by experimental studies (FTIR, CD, SEM, AFM, and rheology) and molecular dynamics simulations. The injectable dipeptide hydrogels were certified as an ideal endoscopic submucosal dissection filler to make operation convenient and secure in mice and living mini-pig's experiments with a longer duration time, higher stiffness, and lower inflammatory response than commercial clinical fillers.

6.
Biomater Sci ; 8(11): 3072-3077, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32270804

RESUMO

Triplet-triplet annihilation upconversion (TTA-UC) has great potential in many fields. However, a stable TTA-UC system with adjustable UC efficiency in non-deoxygenated water is still in urgent demand. Here, the first example of short peptide-tuned UC luminescence in water is reported. With only a small amount of peptides, UC chromophores can assemble into tetrahedral microrods with adjustable size and UC efficiency. Successful TTA-UC luminescence of these microrods in water is achieved due to the regular and dense organization of molecular upconversion chromophores tuned by peptides, which allows rapid triplet exciton migration, avoids aggregation-induced quenching and screens molecular oxygen to upconversion chromophores.

7.
ACS Appl Mater Interfaces ; 11(50): 46419-46426, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31769283

RESUMO

Supramolecular hydrogels self-assembled from short peptides have shown great potential as biomimetic extracellular matrices with controllable properties designed at the molecular level. However, their weak mechanical strength still remains a big challenge for 3D bioprinting. Herein, two oppositely charged dipeptides are designed and used as bioinks in a ″layer-by-layer″ alternative bioprinting strategy. During printing, in situ gelation is achieved by electrostatic interactions between two dipeptides without additional cross-linking procedures. The binary hydrogels have tunable mechanical properties with elastic moduli ranging from 4 to 62 kPa and controllable biodegradability from days to weeks, which can ideally mimic the natural environment of a variety of cell types. It is demonstrated that the hydrogel scaffold enables the formation, growth, and natural release of HepaRG spheroids with sizes up to millimeters. This strategy may be suitable to develop a series of new bioink materials based on peptides and other supramolecular polymers for 3D bioprinting.


Assuntos
Bioimpressão/métodos , Dipeptídeos/química , Hidrogéis/química , Engenharia Tecidual , Matriz Extracelular/química , Fenômenos Mecânicos , Impressão Tridimensional , Esferoides Celulares , Tecidos Suporte
8.
PeerJ ; 7: e7705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598423

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers. Methods: Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC. Results: A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc. Conclusion: Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.

9.
Chem Commun (Camb) ; 55(22): 3191-3194, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30734038

RESUMO

Peptide-based nanoparticles were employed to load and disperse hydrophobic porphyrins in a one-step co-assembly method in aqueous media. The isolated porphyrins doped within nanoparticles showed enhanced two-photon absorption ability and could effectively generate 1O2 to induce the apoptosis of cancer cells, which holds great prospects in two-photon PDT.


Assuntos
Nanopartículas/química , Peptídeos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Porfirinas/química , Apoptose , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fótons , Eletricidade Estática
10.
Soft Matter ; 15(8): 1704-1715, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30724947

RESUMO

Peptide-based hydrogels have been proven to be preeminent biomedical materials due to their high water content, tunable mechanical stability, great biocompatibility and excellent injectability. The ability of peptide-based hydrogels to provide extracellular matrix-mimicking environments opens up opportunities for their biomedical applications in fields such as drug delivery, tissue engineering, and wound healing. In this review, we first describe several methods commonly used for the fabrication of robust peptide-based hydrogels, including spontaneous hydrogelation, enzyme-controlled hydrogelation and cross-linking-enhanced hydrogelation. We then introduce some representative studies on their applications in drug delivery and antitumor therapy, antimicrobial and wound healing materials, and 3D bioprinting and tissue engineering. We hope that this review facilitates the advances of hydrogels in biomedical applications.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Peptídeos/química , Humanos
11.
ACS Appl Mater Interfaces ; 11(4): 4408-4415, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30604609

RESUMO

Microgel loading with inorganic nanoparticle (NP) composites attracts interest for various biomedical applications. However, the encapsulation of NPs into microgels usually is a diffusion process driven by osmotic pressure, which depends highly on the concentration of NPs and causes low loading efficiency. In this work, we demonstrate preparation of microgels with ultrahigh content of various nano-objects (up to 92%, wt %) by a gelatin "casting" strategy using porous CaCO3 particles as templates. This approach could encapsulate various NPs with different charged, hydrophilic, and hydrophobic surfaces, shape, and size within microgels, without causing aggregation or change of physicochemical properties of NPs. The hybrid microgels coupled with properties of both inorganic NPs and hydrogels can be taken as an effective photothermal therapy system with great stability, reusability, and degradability and show high effective photothermal activity which is highly related to the content of NPs within microgels. The strategy of fabrication of microgels with nanocomposites is certified to be simple, facile, and low cost, which has potential applications in cancer therapy, drug delivery, catalysis, detecting system, and sewage treatment.


Assuntos
Hidrogéis/química , Nanocompostos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas
12.
BMC Microbiol ; 18(1): 136, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30336787

RESUMO

BACKGROUND: Dickeya zeae is the causal agent of maize and rice foot rot diseases, but recently it was also found to infect banana and cause severe losses in China. Strains from different sources showed significant diversity in nature, implying complicated evolution history and pathogenic mechanisms. RESULTS: D. zeae strains were isolated from soft rot banana plants and ornamental monocotyledonous Clivia miniata. Compared with D. zeae strain EC1 isolated from rice, clivia isolates did not show any antimicrobial activity, produced less extracellular enzymes, had a much narrow host ranges, but released higher amount of extracellular polysaccharides (EPS). In contrast, the banana isolates in general produced more extracellular enzymes and EPS than strain EC1. Furthermore, we provided evidence that the banana D. zeae isolate MS2 produces a new antibiotic/phytotoxin(s), which differs from the zeamine toxins produced by rice pathogen D. zeae strain EC1 genetically and in its antimicrobial potency. CONCLUSIONS: The findings from this study expanded the natural host range of D. zeae and highlighted the genetic and phenotypic divergence of D. zeae strains. Conclusions can be drawn from a series of tests that at least two types of D. zeae strains could cause the soft rot disease of banana, with one producing antimicrobial compound while the other producing none, and the D. zeae clivia strains could only infect monocot hosts. D. zeae strains isolated from different sources have diverse virulence characteristics.


Assuntos
Amaryllidaceae/microbiologia , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidade , Musa/microbiologia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Bactérias/genética , China , Variação Genética , Filogenia , Virulência
13.
ACS Appl Mater Interfaces ; 10(34): 28420-28427, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30067331

RESUMO

Employing nanoscaled materials as photosensitizer (PS) carriers is an effective strategy to solve the problem of poor solubility and low tumor selectivity of hydrophobic PS in photodynamic therapy (PDT), which compulsorily requires the PS release in PDT implementation. However, the complicated environment in vivo makes it difficult to precisely design and control the release process and the delivery process requires real-time tracking. Developing a delivery strategy of hydrophobic PS in the monomeric form with fluorescent emission and without consideration of the PS release in the PDT process, is in urgent demand. Herein, we report a versatile and potent strategy for fabrication of photodynamic nanoparticles (nanoPSs) with featuring the monomeric PS based on aromatic peptide-modulated self-assembly of porphyrin derivatives. Aromatic peptides within nanoPSs can isolate hydrophobic porphyrins from each other, resulting in monomeric porphyrin delivery with real-time fluorescence tracking property and avoiding self-aggregation and hence porphyrin release. Moreover, partially charged porphyrins tend to expose on the surface of nanoPSs, facilitating production and diffusion of 1O2. The highest 1O2 yield can be achieved with porphyrin loading as low as 6 wt %, reducing side effects of excessive porphyrin injection. The nanoPSs show enhanced PDT efficacy in vitro and in vivo leading to complete tumor eradication. This study highlights opportunities for development of active photodynamic nanoparticles and provides an alternative strategy for delivery of hydrophobic photosensitive drugs with enhanced therapeutic effects.


Assuntos
Fármacos Fotossensibilizantes/química , Nanopartículas , Peptídeos , Fotoquimioterapia , Porfirinas
14.
ACS Nano ; 12(2): 1455-1461, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29361225

RESUMO

Plant thylakoids have a typical stacking structure, which is the site of photosynthesis, including light-harvesting, water-splitting, and adenosine triphosphate (ATP) production. This stacking structure plays a key role in exchange of substances with extremely high efficiency and minimum energy consumption through photosynthesis. Herein we report an artificially designed honeycomb multilayer for photophosphorylation. To mimic the natural thylakoid stacking structure, the multilayered photosystem II (PSII)-ATP synthase-liposome system is fabricated via layer-by-layer (LbL) assembly, allowing the three-dimensional distributions of PSII and ATP synthase. Under light illumination, PSII splits water into protons and generates a proton gradient for ATP synthase to produce ATP. Moreover, it is found that the ATP production is extremely associated with the numbers of PSII layers. With such a multilayer structure assembled via LbL, one can better understand the mechanism of PSII and ATP synthase integrated in one system, mimicking the photosynthetic grana structure. On the other hand, such an assembled system can be considered to improve the photophosphorylation.


Assuntos
Trifosfato de Adenosina/metabolismo , Materiais Biomiméticos/metabolismo , Lipossomos/metabolismo , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Plantas/metabolismo , Tilacoides/metabolismo , Materiais Biomiméticos/química , Lipossomos/química , ATPases Mitocondriais Próton-Translocadoras/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Fotofosforilação , Complexo de Proteína do Fotossistema II/química , Plantas/química , Prótons , Tilacoides/química
15.
Chem Asian J ; 11(19): 2667-2670, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27166977

RESUMO

Nanotube-nanoparticle composites are fabricated by template-directed automatic layer-by-layer assembly with the assistance of pressure. This assembly strategy above allows the facile construction of uniform complex nanostructures with ultra-multilayers (≈200). Importantly, it takes much less time than conventional manual manipulation.

16.
Chem Commun (Camb) ; 51(65): 13044-6, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26186258

RESUMO

Multilayer film coated CaCO3 microspheres were employed as pH responsive ATP carriers to drive kinesin movement. The production of oxygen scavengers in a kinesin-microtubule system induces the decomposition of ATP-loaded CaCO3 microspheres and then leads to the release of ATP.


Assuntos
Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/metabolismo , Carbonato de Cálcio/química , Preparações de Ação Retardada/química , Cinesina/metabolismo , Animais , Concentração de Íons de Hidrogênio , Microesferas , Modelos Moleculares , Movimento
17.
Nanoscale ; 7(1): 82-5, 2015 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-25254951

RESUMO

A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time.


Assuntos
Preparações de Ação Retardada/química , Cinesina/química , Microtúbulos/química , Proteínas Motores Moleculares/química , Nanocápsulas/química , Robótica/métodos , Cinesina/ultraestrutura , Teste de Materiais , Microtúbulos/ultraestrutura , Proteínas Motores Moleculares/ultraestrutura , Movimento (Física) , Nanocápsulas/ultraestrutura , Tamanho da Partícula
18.
Nano Lett ; 14(11): 6160-4, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25303630

RESUMO

LbL-assembled tubes were employed for micro/nanoscale cargo transportation through the kinesin-microtubule system. Selectively modified with kinesins onto the inner tube walls through Ni-NTA complexes, these tubes can work as channels for microtubules. A motility assay shows the smooth movement of microtubules along the tube inner wall powered by the inside immobilized kinesins. It could be envisioned that cargoes with different sizes can be transported through these tubular channels with little outside interruption.

19.
Zhongguo Zhen Jiu ; 31(8): 692-6, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21894689

RESUMO

OBJECTIVE: To verify the efficacy on autism treated with scalp acupuncture for regaining the consciousness and opening the orifice in children. METHODS: Seventy cases of child autism were divided into an observation group (30 cases) and a control group (40 cases). In observation group, the cases were treated with scalp acupuncture for regaining the consciousness and opening the orifice, in combination with music therapy and structure education method. Scalp acupuncture was applied to intelligent nine needles (frontal five needles, Sishencong (EX-HN 1)), affection area, heart and liver area, once a day, at the interval once every one week. Totally, 60 treatments made one session. In control group, music therapy and structure education method were applied simply. Clancy Autism Behavior Scale, Childhood Autism Behavior Scale (CARS), Autism Behavior Checklist (ABC) and Gesell Developmental Scale (social adaptive behaviors and language development) were adopted to assess the scores before treatment and after 1 session of treatment. RESULTS: After treatment, the scores in Clancy Autism Behavior Scale, CARS and ABC were lower apparently in observation group as compared with those before treatment (all P < 0.01), and the scores in Clancy Autism Behavior Scale and ABC were lower than those in control group (both P < 0.01). In observation group, the scores of social adaptive behavior scale and language development scale were improved obviously after treatment (both P < 0.01), which were all higher than those in control group (both P < 0.01). In observation, between the group aged from 4 to 6 years and the group aged from 2 to 3 years, the value differences in Clancy Autism Behavior Scale, ABC and social adaptive development scale did not present statistical significance in group comparison before and after treatment (all P > 0.05). CONCLUSION: Scalp acupuncture for regaining the consciousness and opening the orifice can significantly improve the efficacy on autism, effectively relieve child autism symptoms and enhance the intelligence, language ability and social adaptive ability. Moreover, the efficacy cannot be impacted by child's age.


Assuntos
Terapia por Acupuntura , Transtorno Autístico/terapia , Couro Cabeludo , Adaptação Psicológica , Transtorno Autístico/psicologia , Comportamento Infantil , Pré-Escolar , Feminino , Humanos , Masculino
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