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1.
Sci Rep ; 14(1): 6860, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38514725

RESUMO

When testing earthquake simulation shaking tables, it is commonly assumed that the test load, table, and actuator are integrated, which differs significantly from the actual situation and negatively impacts the accuracy of system waveform reproduction. This paper simplifies the connection between the three as a spring-damping model for simulation modeling. The effects of different load mass, different connection intrinsic frequency, different connection damping ratios, and other factors on the control performance of the system are analyzed, and based on the results of the analysis, a method to improve the effects of the connection characteristics on the performance of the system, called flexible connection reaction force compensation algorithm, is proposed. Resonance peaks caused by flexible connections reduce the effective bandwidth. To broaden the bandwidth and enhance system stability, the paper introduces a flexible connection force compensation algorithm based on a multi-parameter control algorithm to compensate for the interaction force caused by the connection characteristics. This compensation strategy expands the effective bandwidth, eliminates resonance peaks, improves the waveform correlation coefficient (CC), and reduces the root-mean-square error (RMSE).

2.
FASEB J ; 38(5): e23526, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430456

RESUMO

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.


Assuntos
Barreira Hematotesticular , Histona Desacetilases , Células de Sertoli , Animais , Masculino , Camundongos , Barreira Hematotesticular/metabolismo , Diferenciação Celular , Células de Sertoli/metabolismo , Espermatócitos/metabolismo , Espermatogênese/genética , Testículo/metabolismo , Junções Íntimas/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo
3.
Front Oncol ; 14: 1337219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380369

RESUMO

Background: Laparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models' performance. Methods: We retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model. Results: A total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors. Conclusions: This study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

4.
J Colloid Interface Sci ; 661: 740-749, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38325172

RESUMO

Perovskite nanocrystals (PNCs) have attracted extensive attention for their potential applications in biology. However, only a handful of PNCs have been scrutinized in the biological domain due to issues such as instability, poor dispersion, and size inhomogeneity in polar solvents. The development of dual-functional perovskite nanomaterials with hydrogen sulfide (H2S) sensing and antibacterial capabilities is particularly intriguing. In this study, we prepared chiral quasi-two-dimensional (quasi-2D) perovskite nanomaterials, Bio(S-PEA)2CsPb2Br7 and Bio(R-PEA)2CsPb2Br7, that were uniformly dispersed in aqueous media. The effective encapsulation of methoxypolyethylene glycol amine (mPEG-NH2) improved water stability and uniformity of particle size. Circular dichroism (CD) signals were created by the successful insertion of chiral cations. These perovskites as probes showed a rapid and sensitive fluorescence quenching response to H2S, and the effect of imaging detection was observed at the Escherichia coli (E. coli) level. As antibacterial agents, their pronounced positive charge properties facilitated membrane lysis and subsequent E. coli death, indicating a significant antibacterial effect. This work has preliminary explored the application of chiral perovskites in biology and provides insight into the development of bifunctional perovskite nanomaterials for biological applications.


Assuntos
Compostos de Cálcio , Sulfeto de Hidrogênio , Óxidos , Polietilenoglicóis , Titânio , Sulfeto de Hidrogênio/farmacologia , Escherichia coli , Água , Antibacterianos/farmacologia
5.
Virulence ; 14(1): 2265108, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37941402

RESUMO

The control of Ostrinia furnacalis, a major pest of maize in Xinjiang, is challenging owing to the occurrence of resistant individuals. Entomopathogenic fungi (EPF) are natural insect regulators used as substitutes for synthetic chemical insecticides. The fungus Aspergillus nomius is highly pathogenic to O. furnacalis; however, its virulence characteristics have not been identified. This study aimed to analyse the lethal efficacy, mode of infection on the cuticle, and extracellular enzyme activity of A. nomius against O. furnacalis. We found that the mortality and mycosis of O. furnacalis were dose-dependent when exposed to A. nomius and varied at different life stages. The egg-hatching and adult emergence rates decreased with an increase in conidial suspension. The highest mortality (83.33%, 7 d post-infection [DPI]) and mycosis (74.33%, 7 DPI) and the lowest mortality response (8.52 × 103 conidia mL-1) and median lethal time (4.91 d) occurred in the 3rd instar larvae of O. furnacalis. Scanning electron microscopy indicated that numerous conidia germination and infection structure formation may have contributed to the high pathogenicity of A. nomius against O. furnacalis. There were significant correlations between O. furnacalis mortality and the activities of extracellular protease, lipase, and chitinase of A. nomius. This study revealed the infection process of the highly pathogenic A. nomius against O. furnacalis, providing a theoretical basis and reference for strain improvement and field application of EPF.


Assuntos
Lepidópteros , Mariposas , Humanos , Animais , Lepidópteros/microbiologia , Zea mays , Virulência , Mariposas/fisiologia , Aspergillus , Larva/fisiologia
6.
Small ; : e2308600, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974554

RESUMO

The rise of MXene-based materials with fascinating physical and chemical properties has attracted wide attention in the field of biomedicine, because it can be exploited to regulate a variety of biological processes. The biomedical applications of MXene are still in its infancy, nevertheless, the comprehensive evaluation of MXene's biosafety is desperately needed. In this review, the composition and the synthetic methods of MXene materials are first introduced from the view of biosafety. The evaluation of the interaction between MXene and cells, as well as the safety of different forms of MXene applied in vivo are then discussed. This review provides a basic understanding of MXene biosafety and may bring new inspirations to the future applications of MXene-based materials in biomedicine.

8.
Nanoscale ; 15(4): 1947-1952, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36625286

RESUMO

Low-temperature fuel cells have great application potential in electric vehicles and portable electronic devices, which need advanced electrocatalysts. Controlling the composition and morphology of electrocatalysts can effectively improve their catalytic performance. In this work, a Rh metallene (Rhlene)-supported Pt nanoparticle (Pt/Rhlene) electrocatalyst is successfully synthesized by a simple chemical reduction method, in which ultra-small Pt nanoparticles are uniformly attached to the Rhlene surface due to the high surface area of Rhlene. Pt/Rhlene reveals a 3.60-fold Pt-mass activity enhancement for the ethylene glycol oxidation reaction in alkaline solution compared with commercial Pt black, and maintains high stability and excellent poisoning-tolerance during electrocatalysis, owing to the specific physical/chemical properties of Rhlene. The superior electrocatalytic performance of Pt/Rhlene may open an avenue to synthesize other metallene-supported noble metal nanoparticle hybrids for various electrocatalytic applications.

9.
Anal Chim Acta ; 1241: 340778, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36657871

RESUMO

Endogenous peroxynitrite plays a very important role in the regulation of life activities. However, validated tools for ONOO- tests are currently insufficient. We designed a fluorescent probe TPA-F-NO2 with a low fluorescence background in water based on the D-π-A structure for the imaging of endogenous ONOO- in living cells. TPA-F-NO2 can realize the naked eye detection of ONOO- due to the obvious color change. TPA-F-NO2 has the advantages of large stokes shift, high signal-to-noise ratio, high selectivity and sensitivity. The quantitative detection can be achieved in the range of 0-14 µM ONOO-. Due to its solvatochromic characteristics, TPA-F-NO2 has the potential to be used in OLEDs and other fields. In addition, 4-methylumbelliferone has a wide range of anticancer effects as an inhibitor of hyaluronic acid. We prepared TPA-MU-NPs by assembling TPA-F-NO2 and 4-methylumbelliferone. It also endows TPA-MU-NPs with ONOO- imaging function and anti-proliferation effect on breast cancer cells and other cells. This 'probe-drug' assembly strategy provides ideas for the design and optimization of dual-functional probes.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Humanos , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/química , Ácido Peroxinitroso/química , Himecromona , Dióxido de Nitrogênio , Imagem Óptica
10.
Front Psychol ; 14: 1278899, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187415

RESUMO

As positive psychology is imported into second language acquisition, we witness the increasing interest in the research of English enjoyment. Therefore, investigating the antecedents of English enjoyment is of paramount importance. Although internal and external factors have been scrutinized by researchers, scarce studies have explored the effect of peer support and regulatory emotional self-efficacy on English enjoyment. Thus, this study was designed to further clarify the association between these two constructs and English enjoyment. A questionnaire involving the three variables of peer support, English enjoyment, and regulatory emotional self-efficacy was administered to 324 non-English major undergraduate students at a comprehensive university in Eastern China. Correlation analysis and mediation effect tests indicated that peer support and regulatory emotional self-efficacy positively predicted English enjoyment, and regulatory emotional self-efficacy played a mediating role between peer support and English enjoyment. This study highlights the significance of peer support and positive emotions in second language learning and extends our understanding of enhancing students' learning enjoyment through teachers' positive intervention to facilitate peer support and regulatory emotional self-efficacy.

11.
PLoS One ; 17(12): e0279092, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36576934

RESUMO

It is difficult to accurately establish a model of the real mesa system. Furthermore, a model of a seismic simulation vibration table array system is critical to increasing the accuracy of seismic testing in laboratory settings. Herein a model of the nine subarray shaking table system is identified by recursive extension of the least square method, which is used to accurately identify the structure parameters by simulation of the structure assuming a single degree-of-freedom. Then, through the displacement of the empty shaking table and the application of the recursive least squares algorithm, the model of the seismic simulation vibration table array is established. Through this study, the vibration table model of different construction forms can be obtained, and the parameters that are difficult to measure for some complex structures can effectively be determined.


Assuntos
Algoritmos , Vibração , Simulação por Computador , Análise dos Mínimos Quadrados
12.
Chem Commun (Camb) ; 58(79): 11139-11142, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36106578

RESUMO

Electrostatically assembled ultrathin rhodium nanosheet-gold nanowire nanocomposites (Rh-Au CNSs) were used as an advanced electrocatalyst for the methanol oxidation reaction, which revealed a mass activity of 355 mA mgRh-1 at 0.607 V potential, much higher than single metal Rh nanosheets (273 mA mgRh-1) and commercial Rh nanoparticles (165 mA mgRh-1).

13.
J Appl Microbiol ; 133(5): 2979-2992, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35943823

RESUMO

AIMS: This study aimed to isolate and identify entomopathogenic fungi (EPF) from fungus-infected Ostrinia furnacalis larvae, screen their bio-efficacy against O. furnacalis, and select the most suitable virulent native EPF for biocontrol agent development. METHODS AND RESULTS: The occurrence of EPF isolated from various maize production regions in Xinjiang was investigated. Of 13,864 O. furnacalis cadavers surveyed, 536 were selected, and of 136 fungal specimens collected, 14 species were identified. Four fungal isolates were highly pathogenic to O. furnacalis: Aspergillus sp., Lecanicillium attenuatum, Beauveria bassiana and Penicillium polonicum. The Aspergillus sp. was the most abundant (42.25% distribution frequency). Bioassay results revealed that it was as pathogenic as B. bassiana (positive control), with 96.58% lethality against O. furnacalis (LC50 : 1.40 × 104 conidia ml-1 , LT50 : 3.41 days). Through morphological examination and rDNA-benA and rDNA-CaM homogeneity analyses, the isolate was identified as Aspergillus nomius. CONCLUSIONS: Four EPF species were highly pathogenic, with A. nomius being the most prevalent in Xinjiang. A. nomius is a potential biocontrol agent. SIGNIFICANCE AND IMPACT OF STUDY: For sustainable prevention and control of O. furnacalis infestation, identifying biocontrol agents with high virulence against O. furnacalis is crucial. The findings of this study support the development of EPF-based biocontrol approaches.


Assuntos
Beauveria , Mariposas , Animais , Zea mays/genética , Larva/microbiologia , Beauveria/genética , DNA Ribossômico
14.
Sci Adv ; 8(34): eabq2945, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36001654

RESUMO

Meiosis entry during spermatogenesis requires reprogramming from mitotic to meiotic gene expression profiles. Transcriptional regulation has been extensively studied in meiosis entry, but gain of function for master transcription factors is insufficient to down-regulate mitotic genes. RNA helicase YTHDC2 and its partner MEIOC emerge as essential posttranscriptional regulators of meiotic entry. However, it is unclear what governs the RNA binding specificity of YTHDC2/MEIOC. Here, we identified RNA binding protein RBM46 as a component of the YTHDC2/MEIOC complex. Testis-specific Rbm46 knockout in mice causes infertility with defective mitotic-to-meiotic transition, phenocopying global Ythdc2 or Meioc knockout. RBM46 binds to 3' UTR of mitotic transcripts within 100 nucleotides from YTHDC2 U-rich motifs and targets these transcripts for degradation. Dysregulated RBM46 expression is associated with human male fertility disorders. These findings establish the RBM46/YTHDC2/MEIOC complex as the major posttranscriptional regulator responsible for down-regulating mitotic transcripts during meiosis entry in mammalian spermatogenesis, with implications for understanding meiosis-related fertility disorders.


Assuntos
Meiose , Proteínas de Ligação a RNA , Espermatogênese , Animais , Humanos , Masculino , Camundongos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Mamíferos/metabolismo , Meiose/genética , Camundongos Knockout , RNA Helicases/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Espermatogênese/genética , Testículo/metabolismo
15.
Food Chem ; 394: 133477, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35728469

RESUMO

A pulsed electric field (PEF) treatment exhibits different effects on trypsin; however, the mechanism of enzyme activation remains unclear. Herein, chemical experiments combined with molecular dynamics simulations revealed the mechanism of trypsin activation by PEF treatment at the molecular level. The results indicated that compared with the values at 0 kV/cm, the enzyme activity, Vmax, and Kcat at 20 kV/cm increased by 9.30%, 4.74%, and 4.30%, respectively, and Km decreased by 11.14%, indicating an improved interaction between the enzyme and substrate. The simulation results revealed that PEF treatment increased the number of molecular hydrogen bonds and the solvent-accessible surface area, while decreasing the rotation radius and random coil content by 5.00% and 3.37%, respectively. Molecular docking indicated that PEF treatment altered the active center and increased the affinity between the enzyme and substrate. The simulation results were consistent with those of the spectroscopic experiments conducted on trypsin after PEF treatment.


Assuntos
Eletricidade , Simulação de Dinâmica Molecular , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Tripsina
16.
Genes Genomics ; 44(12): 1577-1591, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35567714

RESUMO

BACKGROUND: It has been well established that the long non-coding RNAs (lncRNAs) plays a critical role in tumor progression. However, the function of these transcripts and mechanisms responsible for their deregulation in colorectal cancer (CRC) remain to be investigated. OBJECTIVE: To explore the potential effect and regulation mechanism of lncRNA H19X in colorectal cancer. METHODS: We predicted and validated long non-coding RNA H19X from microarray data of colorectal cancer tissues. In addition, the biological behaviors of H19X and miR-503-5p on CRC were examined in vitro and in vivo, including MTT, colony formation assay, Hoechst33342 and transwell assay. The mRNA and protein levels of KN Motif and Ankyrin Repeat Domains 1 (KANK1) were analyzed by Quantitative real-time PCR (qRT-PCR), western blotting (WB) assay. Moreover, bioinformatics tools and dual-luciferase reporter assay were applied to demonstrate the relationship between KANK1 and miR-503-5p. RESULTS: H19X was remarkably up-regulated in CRC tissues. Its expression related to tumor size (p = 0.041), lymph node metastasis (p = 0.037), distal metastasis (p = 0.028), advanced TNM stage (p = 0.034) and poor survival in CRC. H19X acted as an oncogenic lncRNA that induced CRC cell proliferation, invasion and metastasis. Through a number of functional studies, we found that H19X silencing inhibited the malignance phenotype of cancer cells through loss of miR-503-5p. Further studies demonstrated that miR-503-5p was involved in the progression of CRC by directly regulating the downstream target KANK1. CONCLUSION: Collectively, the findings of the present study indicate H19X/miR-503-5p/KANK1 axis has critical role in the progression of colorectal cancer, providing an effective prognostic indicator and promising target in treatment of colorectal cancer.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Invasividade Neoplásica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal
17.
Pharmaceutics ; 13(12)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34959340

RESUMO

Small interfering RNA (siRNA) can specifically silence disease gene expression. This project investigated the overexpression of programmed death receptor ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) on the surface of tumor cells. However, the main obstacle to the development of gene therapy drugs is the lack of an efficient delivery vector, which should be able to overcome multiple delivery barriers and protect siRNA to enter the target cells. Therefore, a novel fluorine-modified endogenous molecular carrier TFSPEI was constructed by linking fluorinated groups with hydrophobic and hydrophilic characteristics on the surface of PEI and spermine. The results showed that lower toxicity, higher endocytosis, and silencing efficiency were achieved. We found that the inhibition of VEGF targets can indirectly activate the immune response to promote the tumor-killing and invasion effects of T cells. The combined delivery of anti-VEGF siRNA and anti-PD-L1 siRNA could inhibit the expression of corresponding proteins, restore the anti-tumor function of T cells and inhibit the growth of neovascularization, and obtained significant anti-tumor effects. Therefore, this safe and efficient fluorinated spermine and small molecule PEI-based anti-PD-L1 and anti-VEGF siRNA delivery system is expected to provide a new strategy for gene therapy of tumors.

18.
J Gastrointest Oncol ; 12(4): 1543-1557, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532109

RESUMO

BACKGROUND: RNA binding proteins (RBPs) play an important role in regulating post-transcriptional gene expression and have been reported to be closely associated with the occurrence and development of tumors. However, the effect of RBPs in colon cancer remains unclear. METHODS: We downloaded clinical information and transcriptome data of colon adenocarcinoma (COAD) from The Cancer Genome Atlas database (TCGA) database. After combining this data, we identified differentially expressed RBPs in normal and cancer tissues and subsequently performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Prognosis-related RBPs were identified via Cox regression analysis. The samples were randomly divided into two groups; an experimental group and a control group. A predictive model was constructed by dividing the experimental group into high- and low-risk subgroups based on the scores of the prognostic-related RBPs, and the prognosis of samples in these two subgroups was compared. Then, this model was applied to the control group. Finally, the model results were verified based on an online survival database and the Human Protein Atlas (HPA) database. RESULTS: A total of 469 differentially expressed RBPs were identified in normal and cancer tissues. Ten prognosis-related RBPs were determined by Cox regression analysis. In the prognostic prediction model, the prognosis of high-risk patients in the experimental group was worse than that in the low-risk group, and the same result was obtained in the control group. In addition, the risk score in the Cox regression analysis showed that the model could be used as an independent prognostic factor (P<0.001). The results of the online survival analysis tool, HPA database, and the model were consistent. CONCLUSIONS: Some specific RBPs are significantly associated with the prognosis of patients with COAD, and this finding may provide important information for the future diagnosis and treatment of patients with COAD.

19.
Food Funct ; 11(7): 6487-6495, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32628240

RESUMO

Endogenous nanoparticles produced during food processing have received considerable attention due to their unique physicochemical properties and potential safety risks. However, the bio-impact of endogenous nanoparticles on cell metabolism has not been fully studied. In this work, the effects of carbon dots (CDs) derived from the Maillard reaction of glucose and lysine on the cellular substance and energy metabolism were assessed using HepG2 cells as a model. When the HepG2 cells were incubated with 10.0 mg mL-1 of CDs, the mitochondrial membrane potential decreased significantly and the mitochondrial function was affected. The extracellular acidification rate and oxygen consumption rate were decreased in comparison to normal cells without CDs. The CDs blocked the glycolysis pathway by reducing the activities of key enzymes including phosphofructokinase and pyruvate kinase. The energy supply pathway of HepG2 cells changed from glycolysis to TCA cycle, but the increase of the TCA cycle flux could not meet the requirements for restoring cell proliferation. The increase of the compensatory flux in the TCA cycle may be the result of up-regulation of the metabolism of glucogenic amino acids and ketogenic amino acids, while lipid metabolism did not seem to be affected in this process.


Assuntos
Carbono/química , Metabolismo Energético/fisiologia , Reação de Maillard , Aminoácidos/metabolismo , Ciclo do Ácido Cítrico/fisiologia , Glucose/metabolismo , Glicólise , Células Hep G2 , Humanos , Metabolismo dos Lipídeos , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Nanopartículas , Consumo de Oxigênio , Piruvato Quinase/metabolismo
20.
Biomater Sci ; 8(8): 2129-2142, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32232257

RESUMO

Hemangioma, one of the most common angiogenic diseases in infants and children, is characterized by the abnormal and aggressive proliferation of vascular endothelial cells. Advanced therapeutic strategies like RNA interference can inhibit the expression of target proteins at the translational level, but they are rarely used in hemangioma treatment owing to the lack of safe carriers. In this study, we showed for the first time that RNAi technology targeting HIF-1α (hypoxia-inducible factor-1 alpha) could benefit hemangioma therapy effectively. Heptafluorobutyric anhydride (HFAA) was used to modify low-molecular-weight PEI (PEI1.8k), and a novel fluorinated polycation carrier named fluorinated PEI (FPEI) was synthesized. Furthermore, HIF-1α-shRNA-pDNA was condensed by FPEI to fabricate FPEI polyplexes. Compared with PEI25k polyplexes, which are usually the gold standard used in gene delivery, FPEI polyplexes showed lower cytotoxicity and higher serum stability, transfection efficiency and gene silencing efficiency both in vitro and in vivo. In addition, we confirmed that FPEI polyplexes could efficiently inhibit the formation of new capillaries and tumor growth in vivo, which may provide a practicable strategy for clinical hemangioma treatment in the future.


Assuntos
Fluorocarbonos/administração & dosagem , Hemangioma/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polietilenoimina/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/administração & dosagem , DNA/química , Endocitose , Feminino , Fluorocarbonos/química , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Plasmídeos , Polietilenoimina/química , Interferência de RNA
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