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1.
Chemistry ; 29(45): e202301024, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37218025

RESUMO

Rapid and scalable self-assembly of an amphiphilic 21-arm star copolymer, (polystyrene-block-polyethylene glycol)21 [(PS-b-PEG)21 ] in aqueous solution has been performed by reverse solvent exchange procedure. Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) reveal the formation of nanoparticles with narrow size distribution. Further investigation indicates a kinetically controlled self-assembly mechanism of the copolymers, in which the star topology of the amphiphilic copolymer and deep quenching condition by reverse solvent exchange are key to accelerate intrachain contraction of the copolymer during phase separation. When interchain contraction dominant over interchain association, nanoparticles with low aggregation number could be formed. Thanks to the high hydrophobic contents of the (PS-b-PEG)21 polymers, the resulted nanoparticles could encapsulate a high capacity of hydrophobic cargo up to 19.84 %. The kinetically controlled star copolymer self-assembly process reported here provides a platform for the rapid and scalable fabrication of nanoparticle with high drug loading capacity (LC), which may find broad range of applications in, for example drug delivery, nanopesticide.

2.
Oral Dis ; 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37486619

RESUMO

OBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.

3.
Oral Dis ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37727981

RESUMO

OBJECTIVE: The objective of the study was to assess the prognostic value of muscle invasion (MI), a key histopathological feature of tumor aggressiveness, and construct a superior prognostic prediction model combining the current TNM staging system. MATERIALS AND METHODS: MI was analyzed in the whole-slide images from a total of 301 patients with primary buccal mucosa squamous cell carcinoma (BMSCC). Survival times of patients with/without MI were evaluated by Kaplan-Meier analysis. MI was further combined with the TNM staging system to explore its predictive value for prognosis. Moreover, 204 cases of head and neck carcinoma from the TCGA database were included. RESULTS: MI positive rate reached to 76% (229/301) in patients with BMSCC. MI was associated with poor overall survival (p = 0.012) and disease-free survival (p = 0.022). The novel system (TNM staging combined with MI) revealed strong predictive performance, with the largest area under the curve (OS: p < 0.001, DFS: p < 0.004). MI and the established classification system were also had good predictive ability in the TCGA cohort. CONCLUSIONS: MI is an independent predictor of poor prognosis of BMSCC. The inclusion of MI in prediction system can augment the risk stratification of patients with oral squamous cell carcinoma and may assist in the clinical decision-making process.

4.
Mikrochim Acta ; 191(1): 50, 2023 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-38141100

RESUMO

A sensitive immunochromatographic assay (ICA) using time-resolved fluorescence microspheres (TRFMs) coupled with an indirect-labeling mode was developed for simultaneously determining 22 kinds of ß-lactams in milk samples. The TRFMs labeled anti-receptor monoclonal antibodies (mAbs) conjugated to penicillin-binding proteins (PBPs) as ternary TRFMs-mAb-PBPs (TMP) nanoscaffolds provide excellent solubility, brightness, and stability. Thanks to the fact that they not only fully expose the binding sites of PBPs, thereby enhancing the biological affinity of PBPs towards the target, but also generated superb fluorescence signals, the versatile TMP manifested unique possibilities as efficient probes for ICA with remarkable enhancement in sensitivity in ß-lactams screening. The results showed that the standard curves of the 22 varying ß-lactams displayed linearity in their respective concentration ranges (R2 > 0.98), with the cutoff values of 1-100 ng/mL. The constructed TMP-ICA was successfully applied to the analysis of real milk, with consistent results compared with liquid chromatography-tandem mass spectrometry (LC-MS), providing an effective method for sensing ß-lactams in food matrices.


Assuntos
Penicilinas , beta-Lactamas , Animais , beta-Lactamas/análise , Penicilinas/análise , Proteínas de Ligação às Penicilinas , Leite/química , Microesferas , Anticorpos/análise , Imunoensaio
5.
Clin Oral Investig ; 27(10): 6097-6109, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37632578

RESUMO

OBJECTS: Changes in condylar position and morphology after mandibular reconstruction are important to aesthetic and functional rehabilitation. We evaluated changes in condylar position and morphology at different stages after mandibular reconstruction using vascularized fibular free flap with condyle preservation. MATERIALS AND METHODS: A total of 23 patients who underwent mandibular reconstruction with fibular flap were included in this retrospective study. CT data of all patients were recorded before surgery (T0), 7 to 14 days after surgery (T1), and at least 6 months after surgery (T2). Five parameters describing the condylar position and 4 parameters describing the morphology were measured in sagittal and coronal views of CT images. The association between clinical characteristics and changes in condylar position and morphology was analyzed. A finite element model was established to investigate the stress distribution and to predict the spatial movement tendency of the condyle after reconstruction surgery. RESULTS: The condylar position changed over time after mandibular reconstruction. The ipsilateral condyles moved inferiorly after surgery (T0 to T1) and continually move anteriorly, inferiorly, and laterally during long-term follow-up (T1 to T2). Contrary changes were noted in the contralateral condyles with no statistical significance. No morphological changes were detected. The relationship between clinical characteristics and changes in condylar position and morphology was not statistically significant. A consistent result was observed in the finite element analysis. CONCLUSION: Condylar positions showed obvious changes over time after mandibular reconstruction with condylar preservation. Nevertheless, further studies should be conducted to evaluate the clinical function outcomes and condylar position. CLINICAL RELEVANCE: These findings can form the basis for the evaluation of short-term and long-term changes in condylar position and morphology among patients who have previously undergone mandibular reconstruction by FFF with condyle preservation.

6.
J Am Chem Soc ; 144(46): 21267-21277, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36374167

RESUMO

Tandem semi-stable complementary domains play an important role in life, while the role of these domains in the folding process of nucleic acid molecules has not been systematically studied. Here, we designed a clean model system by synthesizing sequence-defined DNA-OEG copolymers composed of ssDNA fragments with palindromic sequences and orthogonal oligo(tetraethylene glycol) (OEG) linkers. By altering the lengths of DNA units (6-12 nt) and OEG linkers (Xn = 0-4) separately, we systematically studied how stabilities of tandem complementary domains and connecting flexibilities affect the assembly topology. Combining experimental methods and coarse-grained molecular simulation analysis, distributions of multiple assembled conformations (mainly monomers, dimers, and clusters) were characterized. Both results indicated that tandem semi-stable complementary domains tend to form homogeneous closed circular dimers instead of larger clusters due to the synergistic enhancement effect, and the distributions of each conformation highly depend on flexibilities.


Assuntos
DNA , Polímeros , DNA de Cadeia Simples
7.
Metabolomics ; 18(11): 82, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36282338

RESUMO

INTRODUCTION: Metabolite stability is critical for tissue metabolomics. However, changes in metabolites in tissues over time from the operating room to the laboratory remain underexplored. OBJECTIVES: In this study, we evaluated the effect of postoperative freezing delay time on the stability of metabolites in normal and oral squamous cell carcinoma (OSCC) tissues. METHODS: Tumor and paired normal tissues from five OSCC patients were collected after surgical resection, and samples was sequentially quenched in liquid nitrogen at 30, 40, 50, 60, 70, 80, 90 and 120 min (80 samples). Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry in positive and negative ion modes was used to identify metabolic changes associated with delayed freezing time. The trends of metabolite changes at 30-120 and 30-60 min of delayed freezing were analyzed. RESULTS: 190 metabolites in 36 chemical classes were detected. After delayed freezing for 120 min, approximately 20% of the metabolites changed significantly in normal and tumor tissues, and differences in the metabolites were found in normal and tumor tissues. After a delay of 60 min, 29 metabolites had changed significantly in normal tissues, and 84 metabolites had changed significantly in tumor tissues. In addition, we constructed three tissue freezing schemes based on the observed variation trends in the metabolites. CONCLUSION: Delayed freezing of tissue samples has a certain impact on the stability of metabolites. For metabolites with significant changes, we suggest that the freezing time of tissues be reasonably selected according to the freezing schemes and the actual clinical situation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Metabolômica/métodos , Congelamento , Carcinoma de Células Escamosas de Cabeça e Pescoço , Nitrogênio
8.
Soft Matter ; 18(5): 975-982, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35014653

RESUMO

The newly developed porous liquids known as liquids with permanent microporosity, have considerable application potential in many unknown areas. Herein, a supramolecular system composed of α-cyclodextrin porous liquid, chiral silver nanoparticles and planar conjugated molecules (methylene blue and indigo carmine) was designed and the induced chirality of the system was observed. It was found that the induced chirality can be easily tuned by changing the pH value of the mixture solution. The induced chiral signal of methylene blue in the developed self-assembled supramolecular system occurred when the pH was between 8 and 10, and furthermore the induced chirality of indigo carmine was found when the pH was between 6.5 and 7.5. The intensity of induced chirality decreases upon increasing temperatures and ionic strength. This study may offer a new approach for the creation of a chiral supramolecular system based on host-guest and electrostatic interaction and make cyclodextrin porous liquids promising candidates for applications in chiral induction.

9.
Appl Microbiol Biotechnol ; 106(23): 7857-7866, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36326838

RESUMO

Xenorhabdus can produce a large number of secondary metabolites with insecticidal, bacteriostatic, and antitumor activities. Efficient gene editing tools will undoubtedly facilitate the functional genomics research and bioprospecting in Xenorhabdus. In this study, BlastP analysis using the amino acid sequences of Redαß or RecET recombinases as queries resulted in the identification of an operon (XBJ1_operon 0213) containing RecET-like recombinases encoding genes from the genome of Xenorhabdus bovienii strain SS-2004. Three proteins encoded by this operon was indispensable for full activity of recombineering, namely XBJ1-1173 (RecE-like protein), XBJ1-1172 (RecT-like protein), and XBJ1-1171 (single-strand annealing protein). Using this newly developed recombineering system, a gene cluster responsible for biosynthesis of a novel secondary metabolite (Min16) was identified from X. stockiae HN_xs01 strain. Min16 which exhibited antibacterial and cytotoxic activities was determined to be a cyclopeptide composed of Acyl-Phe-Thr-Phe-Pro-Pro-Leu-Val by using high-resolution mass spectrometry and nuclear magnetic resonance analysis, and was designated as changshamycin. This host-specific recombineering system was proven to be effective for gene editing in Xenorhabdus, allowing for efficient discovery of novel natural products with attractive bioactivities. KEY POINTS: • Screening and identification of efficient gene editing tools from Xenorhabdus • Optimization of the Xenorhabdus electroporation parameters • Discovery of a novel cyclopeptide compound with multiple biological activities.


Assuntos
Produtos Biológicos , Xenorhabdus , Xenorhabdus/genética , Recombinases/genética , Recombinases/metabolismo , Produtos Biológicos/metabolismo , Óperon , Peptídeos Cíclicos/metabolismo
10.
Chin J Physiol ; 65(6): 290-300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36588355

RESUMO

The effect of different duration of exercise preconditioning (EP) on protecting from exhaustive exercise-induced cardiac injury (EECI) has been optimized in rats. Male Sprague-Dawley rats were divided into six groups: the control group, exhaustive exercise (EE) group, EP 20-min + EE group, EP 40-min + EE group, EP 60-min + EE group and EP 80-min + EE group. The EP groups were subjected to treadmill running at the intensity of 74.0% V̇O2 max. Changes of exercise capacity, cardiac pathology, myocardial enzymology, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function were compared. Compared to the C group, the EE group has shown significant decrease of exercise capacity, elevation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTn-I) levels, cardiac morphology change, ECG disturbance, cardiac dysfunction and reduction of myocardial mitochondrial respiration function. Compared to the EE group, the EP groups have shown significant elevation of exercise capacity, decrease of serum NT-proBNP and cTn-I, improvement of cardiac function and myocardial mitochondrial electron transfer pathway complex I, II and IV activity. The correlation analyses showed protection of EP was proportional to EP duration from 20-min to 60-min. EE caused cardiac injury. EP could protect from EECI by alleviating myocardial damage, improving cardiac function and mitochondrial ETP complex I, II and IV activity. EP protection was positively correlated to EP duration from 20-min to 60-min with EP intensity fixed at 74.0% V̇O2 max.


Assuntos
Condicionamento Físico Animal , Corrida , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Miocárdio/metabolismo , Miocárdio/patologia
11.
Int J Mol Sci ; 23(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35409315

RESUMO

Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV-host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways.


Assuntos
Infecções por Coronavirus , Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Alphacoronavirus , Animais , Interações Hospedeiro-Patógeno , Suínos
12.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077190

RESUMO

Since the beginning of the 21st century, humans have experienced three coronavirus pandemics, all of which were transmitted to humans via animals. Recent studies have found that porcine deltacoronavirus (PDCoV) can infect humans, so swine enteric coronavirus (SeCoV) may cause harm through cross-species transmission. Transmissible gastroenteritis virus (TGEV) and PDCoV have caused tremendous damage and loss to the pig industry around the world. Therefore, we analyzed the genome sequence data of these two SeCoVs by evolutionary dynamics and phylogeography, revealing the genetic diversity and spatiotemporal distribution characteristics. Maximum likelihood and Bayesian inference analysis showed that TGEV could be divided into two different genotypes, and PDCoV could be divided into four main lineages. Based on the analysis results inferred by phylogeography, we inferred that TGEV might originate from America, PDCoV might originate from Asia, and different migration events had different migration rates. In addition, we also identified positive selection sites of spike protein in TGEV and PDCoV, indicating that the above sites play an essential role in promoting membrane fusion to achieve adaptive evolution. In a word, TGEV and PDCoV are the past and future of SeCoV, and the relatively smooth transmission rate of TGEV and the increasing transmission events of PDCoV are their respective transmission characteristics. Our results provide new insights into the evolutionary characteristics and transmission diversity of these SeCoVs, highlighting the potential for cross-species transmission of SeCoV and the importance of enhanced surveillance and biosecurity measures for SeCoV in the context of the COVID-19 epidemic.


Assuntos
COVID-19 , Doenças dos Suínos , Vírus da Gastroenterite Transmissível , Animais , Teorema de Bayes , Deltacoronavirus , Humanos , Filogeografia , Suínos , Doenças dos Suínos/epidemiologia , Vírus da Gastroenterite Transmissível/genética
13.
Angew Chem Int Ed Engl ; 61(30): e202202520, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35445515

RESUMO

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self-assembly of a novel l-DNA hydrogel, which inherited the extraordinary physical properties of a d-DNA hydrogel. With the mirror-isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l-DNA hydrogel has been verified both in vitro and in vivo. Hence, this l-DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell-culture matrix and implanted bio-scaffold for long-term biomedical applications.


Assuntos
DNA , Hidrogéis
14.
Langmuir ; 37(1): 339-347, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33356306

RESUMO

Targeting delivery is a promising technique for the therapy of cancers. A molecule FA-EEYSV-NH2, which consists of target recognition site folic acid (FA), dipeptide linker, and peptide drug, was designed as a novel anticancer prodrug. The molecules could self-assemble into nanoparticles at pH 7.0 and nanofibers at pH 5.0. By the aid of pH-responsiveness, the self-assemblies were used purposefully as targeted vehicles of self-delivery prodrugs. The results of cell toxicity and internalization assays have proved that the self-assemblies have good cancer cell selectivity. The selection was mainly attributed to the pH-responsive structure transition of self-assemblies and the FA active-targeting effect. We hope that our work could provide a useful strategy for finely tuning the properties and activities of peptide-based supramolecular nanomaterials, thus optimizing nanomedicines with enhanced performance.


Assuntos
Nanopartículas , Pró-Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ácido Fólico , Concentração de Íons de Hidrogênio , Peptídeos
15.
Chin J Physiol ; 64(2): 97-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938820

RESUMO

To investigate the persistence time and the effectiveness of exercise preconditioning (EP) on myocardial protection in exhausted rats from myocardial enzymes, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function after cessation of exercise training. One hundred and twelve healthy male Sprague-Dawley rats were randomly divided into seven groups (n = 16): control group (CON), exhaustive exercise (EE) group, EP group, and EE after EP (EP + EE); furthermore, EP + EE group was randomly divided into 1D, 3D, 9D, and 18D groups (1D, 3D, 9D, and 18D) and performed exhaustive treadmill exercise at a speed of 30 m/min on the 1st, 3rd, 9th, and 18th days separately after EP exercise stopped. We detected the serum contents of N-terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) by the enzyme-linked immunosorbent assays method, recorded ECG, detected heart function by pressure volume catheter, measured the respiratory rates of rat myocardial mitochondria state 3 and 4 of complex I, complex II, and IV by high-resolution breathing apparatus. EP could decrease the serum content of NT-proBNP and cTnI, improved the electrical derangement and the left ventricular function in exhausted rats. Moreover, the protective effect was more obvious in the 9th day after EP stopped, whereas it would disappear when EP stopped for more than 18 days. Compared with EE group, the respiratory rate value of myocardial mitochondrial complex increased in 1D, 3D, and 9D groups. Therefore, the protective effect of EP on the heart of exhausted rats decreased with the prolongation of stopping training time, and the effect was significant within 3 days of discontinuing training, then decreased gradually, and completely disappeared in the 18th day. EP enhanced the cardiac function in exhausted rats through raising the nicotinamide adenine diphosphate hydride (NADH) electron transport chain and increased the respiration rates of mitochondrial respiratory complex I and IV state 3, thereby improved myocardial mitochondrial respiratory function and energy metabolism.


Assuntos
Condicionamento Físico Animal , Animais , Coração , Masculino , Miocárdio , Ratos , Ratos Sprague-Dawley , Troponina I
16.
Chembiochem ; 21(1-2): 94-97, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31659823

RESUMO

The first thermally stable and pH-responsive quadruplex intercalated motif (i-motif) structure formed by l-DNA is presented. Although this l-type i-motif exhibits the same physiochemical properties as its d isomer, its inverted chirality and good enzymatic resistance potentially open the way to the development of new DNA materials of pharmaceutical and biological interest.


Assuntos
DNA/química , Concentração de Íons de Hidrogênio , Conformação de Ácido Nucleico , Motivos de Nucleotídeos , Termodinâmica
17.
Ecotoxicol Environ Saf ; 204: 111065, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32784014

RESUMO

In the present study, chemical analysis of contaminants (three classes of organic pollutants and seven metals) and elutriate toxicity test were adopted to evaluate the potential environmental hazards of dredged sediment samples from five sites (SS1-5) along Huangpu River Channel (Shanghai Harbor, China). The metal Pb, Cu, Cr, Zn and the organic pollutants including total hexachlorocyclohexane (HCHs) and total dichlorodiphenyltrichloroethane (DDTs) in the five samples exceeded the threshold for effects level (TEL) to varying degrees. The probable effect concentration quotients (QPECm) of contaminants from the five dredged samples were all above 0.25, which means potential toxicity risks. Elutriate toxicity tests using medaka fish (Oryzias melastigma) and manila clam (Ruditapes philippinarum) showed that SS2 caused mortality to both species and SS1 caused mortality to fish. To explore the molecular biomarkers that may reflect the toxic effects, differential expressed genes were identified by RNA-Seq-based transcriptome profiling from the survived clams exposed to the two polluted elutriates (SS1, SS2). In clams exposed to SS1 and SS2 elutriate, 368 and 860 differential expressed genes (DEGs) were up-regulated, 199 and 1304 genes were down-regulated, respectively. Fourteen DEGs were selected from the enriched pathways that reflect cytotoxicity and responses to xenobiotics for the following quantitative real time PCR analysis. The transcriptomic profiling and the selected gene's expression patterns from clams exposed to SS1 and SS2 showed significant differences with the non-contaminated and control groups. Using the expression data of the selected gene battery in Factor Analysis allowed the discrimination between contaminated and non-contaminated sites and may reflect an influence gradient of sites. The development of the assay of these molecular biomarkers may provide a rapid and high-throughput tool for the quality assessment of the dredging sediments.


Assuntos
Bivalves/efeitos dos fármacos , Monitoramento Ambiental/métodos , Expressão Gênica/efeitos dos fármacos , Sedimentos Geológicos/química , Rios/química , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/genética , China , DDT/toxicidade , Hexaclorocicloexano/toxicidade , Metais Pesados/toxicidade , Testes de Toxicidade
18.
J Cell Physiol ; 234(10): 18970-18984, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30916359

RESUMO

Traditional Chinese medicine (TCM) are both historically important therapeutic agents and important source of new drugs. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been shown to exert strong antiproliferative effects that differ markedly among various cell lines. However, whether HF inhibits MCF-7 cell growth in vitro and underlying mechanisms of this process are not yet clear. Here, we offer the strong evidence of the connection between HF treatment, exosome production and proliferation of MCF-7 cells. Our results showed that HF inhibits MCF-7 cell growth in both time- and dose-dependent manner. Further microRNA (miRNA) profiles analysis in HF treated and nontreated MCF-7 cell and exosomes observed that six miRNAs are particularly abundant and sorted in exosomes. miRNAs knockdown experiment in exosomes and the MCF-7 growth inhibition assay showed that exosomal microRNA-31 (miR-31) modulates MCF-7 cells growth by specially targeting the histone deacetylase 2 (HDAC2), which increases the levels of cyclin-dependent kinases 2 (CDK2) and cyclin D1 and suppresses the expression of p21. In conclusion, these data indicate that inhibition of exosome production reduces exosomal miR-31, which targets the HDAC2 and further regulates the level of cell cycle regulatory proteins, contributing to the anticancer functions of HF. Our data suggest a new role for HF and the exosome production in tumorigenesis and may provide novel insights into prevention and treatment of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Exossomos/genética , Histona Desacetilase 2/metabolismo , MicroRNAs/genética , Piperidinas/farmacologia , Quinazolinonas/farmacologia , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Humanos , Células MCF-7 , Medicina Tradicional Chinesa
19.
Langmuir ; 35(40): 13174-13181, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31532218

RESUMO

Novel lipopeptide vesicles are prepared from self-assembled nanomembranes through an extrusion method. The size of vesicles can be controlled by the pore diameter of the extrusion filter. The vesicles are rather stable because hydrogen bonds exist among the peptide headgroups. When doxorubicin hydrochloride (DOX·HCl) is encapsulated in the vesicles, it could be released sustainably, and its side effect would also be reduced due to encapsulation. The leakage rate of DOX·HCl depends on the pH via charge regulation. As drug carriers, lipopeptide vesicles have been proved to have nontoxicity to normal cells. A magnetic surfactant CH3(CH2)14CH2N(CH3)3+ [FeCl3Br]- (CTAFe) was mixed with lipopeptide to modify the vesicles. Also, the results demonstrated that the vesicles is endowed with magnetic property after the addition of CTAFe. We believe that the strategy of lipopeptide vesicle preparation would enrich the drug carrier family and expand the application of lipopeptide materials.

20.
Langmuir ; 35(30): 9841-9847, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31268331

RESUMO

The coassembly behavior of peptide amphiphiles (PAs) C4-Bhc-EE-NH2 and C14-FKK-NH2 has been investigated by transmission electron microscopy, atomic force microscopy, fluorescence microscopy, circular dichroism, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance. These two PAs coassembled into nanofibers by electrostatic and π-π stacking interactions at a low concentration and further aggregated into nanofiber bundles via charge complementation on the surface of nanofibers. As the charge number varied with pH, the bundles could be disassembled/assembled with pH regulation. More interestingly, as C4-Bhc-EE-NH2 was a photodegradable molecule, the bundles could also be responsive to both ultraviolet (UV) and near-infrared (NIR) light. In contrast to the reversible pH-dependent response, the light responses were irreversible as C4-Bhc-EE-NH2 broke under UV or NIR radiation. The highlight of this article is that structural changes were realized for control at the aggregate level, not only at the molecular level. With this inspiration, we hope that we can support the novel biomaterial construction and exploitation of new functions of biomaterials.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Luz , Peptídeos/química , Concentração de Íons de Hidrogênio
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