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1.
Int Immunopharmacol ; 143(Pt 1): 113261, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39353381

RESUMEN

Tumor cells can escape immune surveillance by changing their own escape or expressing abnormal genes and proteins, resulting in unlimited proliferation and invasive growth of cells. These changes are related to microRNAs (miRNAs), which reduce the killing effect of immune cells, devastate the immune response, and interfere with apoptosis through the aberrant expression of relevant miRNAs. In the preliminary phase of this study, miRNAs in clinical plasma exosomes of colorectal cancer patients were differentially analyzed by RNA sequencing technology, and miR-372-5p derived from extracellular vesicles (sEVs) was found to be a key signaling molecule mediating the regulation of macrophages by colorectal cancer (CRC). miRNA-372-5p is upregulated in colorectal cancer patient tissues and serum, as well as colorectal cancer cell lines and their exosomes. Subsequently, we found that macrophages could take up sEV secreted by colorectal cancer cells HCT116, affecting the expression of the immune checkpoint PD-L1, resulting in the generation of a tumor-immunosuppressive microenvironment and suppression of T cell activation in CRC. Gene enrichment mapping and database revealed that miR-372-5p regulates PD-L1 expression in colorectal cancer through the homologous phosphatase-tensin (PTEN)-phosphatidylinositol 3-kinase-protein kinase B (AKT)-nuclear factor-κB (NF-κB) pathway. Further studies confirmed that miRNA-372-5p-treated macrophages co-cultured with T cells affected the regulation of PD-L1 expression through the PTEN/AKT/NF-κB signaling pathway, resulting in decreased CD3+CD8+ T cell activity, decreased cytokine IL-2 and increased IFN-γ. And miRNA-372-5p could down-regulate the expression of PD-L1 in HCT116 through the PTEN/AKT/NF-κB pathway, inhibit tumor cell proliferation and promote apoptosis. Conclusion: Colorectal cancer cell-derived exosome miR-372-5p can be phagocytosed by colorectal cancer and macrophage cells, regulate the expression of PD-L1 in colorectal cancer cells and macrophages by targeting the PTEN/AKT/NF-κB pathway, and induce the immunosuppressive microenvironment of CRC to promote CRC development. This suggests that inhibiting the secretion of HCT116-specific sEV-miR-372-5p or targeting PD-L1 in tumor-associated macrophages could be a novel approach for CRC treatment and possibly a sensitizing approach for CRC anti-PD-L1 therapy.

2.
Front Oncol ; 14: 1452666, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372872

RESUMEN

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125104, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39260240

RESUMEN

A novel method for the rapid identification of hemp fibers is proposed in this paper, utilizing terahertz time-domain spectroscopy (THz-TDS) combined with the LargeVis (LV) dimensionality reduction technique. This approach takes advantage of the strengths of THz-TDS while enhancing classification accuracy through LV. To verify the efficacy of this method, terahertz absorption spectral data from three types of hemp fibers were processed. The THz absorption spectra were initially preprocessed using Hanning filtering. Following this, the filtered data underwent dimensionality reduction through three distinct methods: linear Principal Component Analysis (PCA), nonlinear t-Distributed Stochastic Neighbor Embedding (t-SNE), and the LV method. This sequence of steps resulted in a two-dimensional feature data matrix derived from the THz source spectral data. The resultant feature data matrices were then input into both K-Nearest Neighbors (KNN) and Decision Tree (DT) classifiers for analysis. The classification accuracies of six models were evaluated, revealing that the LV-KNN model achieved a 86.67% accuracy rate for the three hemp fiber types. Impressively, the LV-DT model achieved a perfect 100.00% accuracy rate for the same fibers. The LV-DT model, when integrated with THz spectroscopy technology, offers a quick and precise method for identifying various types of hemp fibers. This development introduces an innovative optical measurement scheme for the characterization of textile materials.

4.
Int Immunopharmacol ; 142(Pt B): 113168, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39298813

RESUMEN

The most frequent cancer in women to be diagnosed is breast cancer, and chemotherapy's ability to be effective is still significantly hampered by drug resistance. Tumor-derived exosomes play a significant role in drug resistance, immunological modulation, metastasis, and tumor proliferation. In this work, the differential miRNAs in the exosomes of drug-resistant and susceptible breast cancer cell lines were screened using miRNA-seq. It was demonstrated that drug-resistant human breast cancer cells and their exosomes expressed more miR-99b-3p than did susceptible cells and their exosomes. While drug-resistant cells' migration and paclitaxel resistance can be inhibited by driving down the expression of miR-99b-3p in those cells, exosomes containing miR-99b-3p from those cells can help susceptible cells migrate and become resistant. miR-99b-3p affects cell migration and paclitaxel resistance by targeting PPP2CA to promote AKT/mTOR phosphorylation. The drug-resistant cell exosome miR-99b-3p can be taken up by macrophages and affect the drug resistance and migration ability of sensitive cells by promoting the M2 polarization of macrophages. Downregulating miR-99b-3p has been shown in vivo to reverse macrophage M2 polarization, suppress tumor development, and prevent treatment resistance. The present study shows that drug-resistant cell exosomes miR-99b-3p can directly influence the migration, proliferation, and paclitaxel sensitivity of sensitive cells via PPP2CA. Additionally, the exosomes from drug-resistant cells can influence the polarization of macrophage M2 in the tumor microenvironment, which can also have an impact on the proliferation, migration, and paclitaxel sensitivity of sensitive cells.


Asunto(s)
Neoplasias de la Mama , Movimiento Celular , Resistencia a Antineoplásicos , Exosomas , Macrófagos , MicroARNs , Paclitaxel , Proteína Fosfatasa 2 , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo , Resistencia a Antineoplásicos/genética , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , Femenino , Movimiento Celular/efectos de los fármacos , Paclitaxel/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Serina-Treonina Quinasas TOR/metabolismo , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-akt/metabolismo
5.
Int J Nanomedicine ; 19: 4199-4215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766657

RESUMEN

Background: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Ferroptosis , Hidróxidos , Simvastatina , Ferroptosis/efectos de los fármacos , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Hidróxidos/química , Hidróxidos/farmacología , Simvastatina/farmacología , Simvastatina/química , Simvastatina/administración & dosificación , Apoptosis/efectos de los fármacos , Animales , Línea Celular Tumoral , Nanopartículas/química , Sinergismo Farmacológico , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Desnudos , Ratones Endogámicos BALB C , Células MCF-7 , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5162-5171, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114106

RESUMEN

This study aims to investigate the impact of the invasive pest Corythucha marmorata on the growth and quality of Artemi-sia argyi. The signs of insect damage at the cultivation base of A. argyi in Huanggang, Hubei were observed. The pests were identified based on morphological and molecular evidence. The pest occurrence pattern and damage mechanism were investigated. Electron microscopy, gas chromatography-mass spectrometry(GC-MS), and high performance liquid chromatography(HPLC) were employed to analyze the microstructure, volatile oils, and flavonoid content of the pest-infested leaves. C. marmorata can cause destructive damage to A. argyi. Small decoloring spots appeared on the leaf surface at the initial stage of infestation. As the damage progressed, the spots spread along the leaf veins and aggregated into patches, causing yellowish leaves and even brownish yellow in the severely affected areas. The insect frequently appeared in summer because it thrives in hot dry conditions. After occurrence on the leaves, microscopic examination revealed that the front of the leaves gradually developed decoloring spots, with black oily stains formed by the black excrement attaching to the glandular hairs. The leaf flesh was also severely damaged, and the non-glandular hairs were broken, disor-ganized, and sticky. The content of neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acids A and B, hispidulin, jaceosidin, and eupatilin at the early stage of infestation was significantly higher than that at the middle stage, and the content decreased at the last stage of infestation. The content of eucalyptol, borneol, terpinyl, and caryophyllin decreased in the moderately damaged leaves and increased in the severely damaged leaves. C. marmorata was discovered for the first time on A. argyi leaves in this study, and its prevention and control deserves special attention. The germplasm materials resistant to this pest can be used to breed C. marmorata-resis-tant A. argyi varieties.


Asunto(s)
Artemisia , Aceites Volátiles , Artemisia/química , Fitomejoramiento , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles/análisis , Cromatografía Líquida de Alta Presión , Hojas de la Planta/química
7.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5474-5486, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114140

RESUMEN

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, ß-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.


Asunto(s)
Artemisia , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Fitomejoramiento , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Gases y Espectrometría de Masas , Artemisia/química , Medicamentos Herbarios Chinos/química
8.
J Clin Oncol ; 41(31): 4829-4836, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37890277

RESUMEN

PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METHODS: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. RESULTS: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P < .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.

9.
Int J Biol Macromol ; 253(Pt 2): 126645, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37659487

RESUMEN

Windmill palm, a tree species that is native to China, has gained attention with regard to the production of substantial amounts of biomass fibers via yearly pruning. This study investigates the structure and thermal properties of cellulose nanofibrils (CNFs) obtained from windmill palm biomass, with the goal of promoting the usage of these CNFs. Alkali-ultrasound treatments are employed herein to prepare samples of the CNFs. The micromorphology of the prepared samples is observed using scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. Furthermore, X-ray diffraction analysis is used to examine the aggregated structure of the samples, and thermogravimetric analysis is used to investigate their thermal properties. Results indicate that during alkali hydrolysis when obtaining CNFs, the fiber cell wall exhibits distinct spiral cracking. The diameter of the obtained nanocellulose is <90 nm. The removal of lignin and hemicellulose materials from the fiber cell enhances the crystallinity of CNFs to as high as 60 %, surpassing that of windmill palm single fibers. The thermal decomposition temperatures of the CNFs are found to be 469 °C and 246 °C for the crystalline and amorphous regions, respectively.


Asunto(s)
Celulosa , Nanofibras , Celulosa/química , Nanofibras/química , Espectroscopía Infrarroja por Transformada de Fourier , Lignina/química , Microscopía Electrónica de Rastreo
10.
Cell Signal ; 111: 110884, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37690660

RESUMEN

Colorectal cancer (CRC) is the most common malignancy in the digestive system, and tumor metastasis is the main cause of death in clinical patients with CRC. It has been shown that exosomes promote phenotypic changes in macrophages and tumor metastasis in the CRC tumor microenvironment. In this study, we used miRNA-seq technology to screen out the highly expressed miR-372-5p among the miRNAs differentially expressed in plasma exosomes of clinical CRC patients. It was found that miR-372-5p highly expressed in HCT116 exosomes could be phagocytosed by macrophages and promote their polarization into M2 macrophages by regulating the PTEN/AKT pathway. Meanwhile, co-culture of CRC cells with conditioned medium (CM) of macrophages enhanced the EMT, stemness and metastasis of CRC cells. Mechanistically, CRC cells exosome-derived miR-372-5p induced polarized M2 macrophages to secrete chemokine C-X-C-Motif Ligand 12 (CXCL12), which activated the WNT/ß-catenin pathway to promote the EMT, stemness and metastatic ability of CRC cells. In summary, this study elucidated the molecular mechanism of exosomal miR-372-5p promoting metastasis and stemness in CRC, which may provide new therapeutic targets for CRC metastasis and prognosis assessment.

11.
J Plant Res ; 136(6): 879-889, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37535187

RESUMEN

Phosphorus is essential in critical plant processes such as signaling, photosynthesis, energy metabolism, and enzyme activity during respiration. Phosphorus stress therefore has a significant impact on plant growth and metabolism. Here, we characterized the biochemical responses of Artemisia argyi Level. et Vant to low phosphorus (LP) and high phosphorus (HP) stress. Plants were treated with 0 g (LP), 1.5 g (control), or 3 g (HP) P per 10 kg of soil. The results demonstrated that CK encouraged the most plant growth, as quantified by leaf size and plant biomass. We also found that the total amounts of phenolic and flavonoid compounds (such as chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, cryptochlorogenic acid, neochlorogenic acid, hispidulin, jaceosidin, eupatilin, and casticin) were increased in the leaves of A. argyi plants exposed to LP stress compared to those raised under CK conditions. The levels of these compounds were inversely related to the amount of phosphorus added, and therefore peaked in plants treated with LP stress. Levels of terpenoids were also found to fluctuate under LP and HP stress compared to CK conditions. Furthermore, transcriptomic analyses showed up-regulation of several genes encoding key enzymes in the flavonoid and phenolic acid metabolic pathways under LP stress. There were also alterations in the expression levels of genes in the methylerythritol 4-phosphate and mevalonate pathways of terpene synthesis. This study contributes to a deeper understanding of the physiological and molecular mechanisms underlying phosphorus stress responses and their impacts on the growth and quality of the economically important species A. argyi.


Asunto(s)
Artemisia , Fósforo , Metabolismo Secundario , Terpenos , Flavonoides
12.
Sci Rep ; 13(1): 12866, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553416

RESUMEN

Nitrogen is a key factor in various physiological and metabolic processes in plants. Providing an adequate supply of nitrogen is essential for improving the total yield and quality of the medicinal plant Artemisia argyi (A. argyi), but the underlying mechanisms of how this nutrient alters the crop remains unclear. In this study, we conducted a series of pot experiments to investigate the agronomic traits and active components in the leaves of A. argyi plants under low and high nitrogen stress. Additionally, we used transcriptome analysis and RT-qPCR to explore the molecular pathways associated with nitrogen stress. Our results demonstrate a dramatic increase in the accumulation of phenolic acids and flavonoids in the low nitrogen (LN) stress group compared to the control (CK), with increases of 40.00% and 79.49%, respectively. Interestingly, plants in the high nitrogen (HN) stress group exhibited enhanced plant growth with larger leaves, thicker stems, and a 3% increase in volatile oil content compared to the CK. Moreover, A. argyi in the HN group displayed a 66% increase in volatile oil concentration compared to the LN group. Our combined transcriptome and q-PCR results indicate that LN stress promotes the expression of genes involved in flavonoid synthesis, while HN stress promotes the expression of genes related to terpene skeleton production and photosynthesis. Taken together, these findings suggest that different gene expression levels under LN and HN stress contribute to the photosynthesis capacity and the accumulation of active ingredients in A. argyi leaves. Our results elucidate the physiological and molecular mechanisms of nitrogen stress on A. argyi secondary metabolites and guide fertilization strategies for plant cultivation.


Asunto(s)
Artemisia , Medicamentos Herbarios Chinos , Aceites Volátiles , Nitrógeno , Artemisia/genética , Hojas de la Planta
13.
Gene ; 885: 147692, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37562585

RESUMEN

(1) Background: Tumor-associated macrophages (TAMs) are important immunocytes associated with liver metastasis of colorectal cancer (CRLM). However, the molecular processes underpinning the interaction between the TME and the tumour-derived exosomal miRNAs in CRLM are not being fully understood; (2) Methods: Transmission electron microscopy was utilized to confirm the existence of exosomes after differential ultracentrifugation. To determine the roles of exosomal miR-203a-3p, an in vivo and in vitro investigation was conducted. The mechanism by which exosomal miR-203a-3p governs the interaction between CRC cells and M2 macrophages was investigated using a dual-luciferase reporter assay, western blot, and other techniques; (3) Results: Overexpression of miR-203a-3p was associated with poor prognosis and liver metastasis in CRC patients. Exosomal miR-203a-3p was upregulated in the plasma of CRC patients and highly metastatic CRC cells HCT116, and it could be transported to macrophages via exosomes. Exosomal miR-203a-3p induced M2 polarization of macrophages by controlling PTEN and activating the PI3K/Akt signaling pathway. M2-polarized macrophages secreted the CXCL12, which increased cancer metastasis and resulted in pre-metastatic niches in CRLM by CXCL12/CXCR4/NF-κB signaling pathway. Co-culture of macrophages with miR-203a-3p-transfected or exosome-treated cells increased the ability of HCT116 cells to metastasize both in vitro and in vivo; (4) Conclusions: Exosomes produced by highly metastatic CRC cells and rich in miR-203a-3p may target PTEN and alter the TME, promoting liver metastasis in CRC patients. These findings offer fresh understanding of the liver metastatic process in CRC.


Asunto(s)
Neoplasias Colorrectales , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Exosomas/metabolismo , Neoplasias Hepáticas/patología , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo
14.
Biomed Pharmacother ; 165: 115009, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37343435

RESUMEN

Tumor cells are able to use glycolysis to produce energy under hypoxic conditions, and even under aerobic conditions, they rely mainly on glycolysis for energy production, the Warburg effect. Conventional tumor therapeutic drugs are unidirectional, lacking in targeting and have limited therapeutic effect. The development of a large number of nanocarriers and targeted glycolysis for the treatment of tumors has been extensively investigated in order to improve the therapeutic efficacy. This paper reviews the research progress of nanocarriers based on targeting key glycolytic enzymes and related transporters, and combines nanocarrier systems with other therapeutic approaches to provide a new strategy for targeted glycolytic treatment of tumors, providing a theoretical reference for achieving efficient targeted treatment of tumors.


Asunto(s)
Antineoplásicos , Sistema de Administración de Fármacos con Nanopartículas , Neoplasias , Efecto Warburg en Oncología , Sistema de Administración de Fármacos con Nanopartículas/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/farmacología , Neoplasias/tratamiento farmacológico , Efecto Warburg en Oncología/efectos de los fármacos , Proteínas Facilitadoras del Transporte de la Glucosa/antagonistas & inhibidores , Hexoquinasa/antagonistas & inhibidores , Fosfofructoquinasas/antagonistas & inhibidores , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Humanos
15.
ACS Omega ; 8(21): 18435-18448, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37273596

RESUMEN

MicroRNAs (miRNAs) play an essential role in cancer therapy, but the disadvantages of its poor inherent stability, rapid clearance, and low delivery efficiency affect the therapeutic efficiency. Loading miRNAs by nanoformulations can improve their bioavailability and enhance therapeutic efficiency, which is an effective miRNA delivery strategy. In this study, we synthesized layered double hydroxides (LDH), which are widely used as carriers of drugs or genes due to the characteristics of good biocompatibility, high loading capacity, and pH sensitivity. We loaded the suppressor oncogene miR-30a on LDH nanomaterials (LDH@miR-30a) and determined the mass ratio of miRNA binding to LDH by agarose gel electrophoresis. LDH@miR-30a was able to escape the lysosomal pathway and was successfully phagocytosed by breast cancer SKBR3 cells and remained detectable in the cells after 24 h of co-incubation. In vitro experiments showed that LDH@miR-30a-treated SKBR3 cells showed decreased proliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30a was able to regulate the epithelial-mesenchymal transition (EMT) process and inhibit cell migration and invasion by targeting SNAI1. Meanwhile, in vivo experiments showed that nude mice treated with LDH@miR-30a showed a significant reduction in their solid tumors and no significant impairment of vital organs was observed. In conclusion, LDH@miR-30a is an effective drug delivery system for the treatment of breast cancer.

16.
Gene ; 860: 147230, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36717039

RESUMEN

The lncRNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) has been associated with the development, metastasis and drug resistance of breast cancer (BC). However, the mechanisms underlying NEAT1-induced paclitaxel resistance in the microenvironment of BC remain unclear. In this study, NEAT1 expression was found to be high in paclitaxel-resistant BC cells (SKBR3/PR cells) and exosomes derived from these cells. NEAT1 promoted the migration of BC cells and their resistance to paclitaxel, whereas its downregulation reduced the drug resistance. In addition, downregulation of NEAT1 decreased the migration and proliferation of BC cells by inhibiting the expression of CXCL12 by reducing the adsorption of miR-133b. Furthermore, inhibition of miR-133b reversed the interference of NEAT1 and CXCL12 in paclitaxel resistance, migration and proliferation of BC cells. Knockdown of NEAT1 in a xenograft-bearing mouse model remarkably inhibited cancer progression and improved the response to paclitaxel. Altogether, this study revealed that SKBR3/PR cell-derived exosomal lncRNA NEAT1 can induce paclitaxel resistance and cell migration and growth in the tumour microenvironment of BC and may serve as a new target for the clinical treatment of BC.


Asunto(s)
Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Paclitaxel/farmacología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Microambiente Tumoral/genética , Resistencia a Antineoplásicos
17.
3 Biotech ; 13(2): 57, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36698769

RESUMEN

Different collections and accessions of Artemisia argyi (Chinese mugwort) harbour considerable diversity in morphology and bioactive compounds, but no mechanisms have been reported that explain these variations. We studied genome size in A. argyi accessions from different regions of China by flow cytometry. Genome size was significantly distinct among origins of these 42 Chinese mugwort accessions, ranging from 8.428 to 11.717 pg. There were no significant intraspecific differences among the 42 accessions from the five regions of China. The clustering analysis showed that these 42 A. argyi accessions could be divided into three groups, which had no significant relationship with geographical location. In a genome survey, the total genome size of A. argyi (A15) was estimated to be 7.852 Gb (or 8.029 pg) by K-mer analysis. This indicated that the results from the two independent methods are consistent, and that the genome survey can be used as an adjunct to flow cytometry to compensate for its deficiencies. In addition, genome survey can provide the information about heterozygosity, repeat sequences, GC content and ploidy of A. argyi genome. The nuclear DNA contents determined here provide a new reference for intraspecific variation in genome size in A. argyi, and may also be a potential resource for the study of genetic diversity and for breeding new cultivar.

18.
Carbohydr Polym ; 297: 119996, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36184129

RESUMEN

Windmill palm fibres are well-known plant fibres exhibiting the largest elongation at break. In this study, lignin or hemicellulose was removed from windmill palm fibres in a targeted manner to prepare materials with different chemical compositions. The structure and mechanical properties of the windmill palm fibres were analysed using in situ scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry, X-ray diffraction analysis and tensile testing. The large elongation at break was attributed to the unwinding of the single fibre, the micro cracks and the small degree of orientation (<62 %). On a microscopic scale, the lumen shape of fibre cross section influences the local stress distribution. The hemicellulose-removed fibres exhibited a high breaking strength of 236 MPa with deterioration of the thermal property. The binding force between single fibres is the weakest after lignin removal. The removal of hard lignin softens the fibres and increases the elongation at break to >30 %.


Asunto(s)
Fibras de la Dieta , Lignina , Lignina/química , Fenómenos Mecánicos , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría
19.
BMC Plant Biol ; 22(1): 368, 2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35879664

RESUMEN

BACKGROUND: Allelopathy is expressed through the release of plant chemicals and is considered a natural alternative for sustainable weed management. Artemisia argyi (A. argyi) is widely distributed throughout Asia, and often dominates fields due to its strong allelopathy. However, the mechanism of A. argyi allelopathy is largely unknown and need to be elucidated at the physiological and molecular levels. RESULTS: In this study, we used electron microscopy, ionomics analysis, phytohormone profiling, and transcriptome analysis to investigate the physiological and molecular mechanisms of A. argyi allelopathy using the model plant rice (Oryza sativa) as receptor plants. A. argyi water extract (AAWE)-treated rice plants grow poorly and display root morphological anomalies and leaf yellowing. We found that AAWE significantly inhibits rice growth by destroying the root and leaf system in multiple ways, including the integrity of ultrastructure, reactive oxygen species (ROS) homeostasis, and the accumulation of soluble sugar and chlorophyll synthesis. Further detection of the hormone contents suggests that AAWE leads to indole-3-acetic acid (IAA) accumulation in roots. Moreover, ionomics analysis shows that AAWE inhibits the absorption and transportation of photosynthesis-essential mineral elements, especially Mg, Fe, and Mn. In addition, the results of transcriptome analysis revealed that AAWE affects a series of crucial primary metabolic processes comprising photosynthesis in rice plants. CONCLUSIONS: This study indicates that A. argyi realizes its strongly allelopathy through comprehensive effects on recipient plants including large-scale IAA synthesis and accumulation, ROS explosion, damaging the membrane system and organelles, and obstructing ion absorption and transport, photosynthesis and other pivotal primary metabolic processes of plants. Therefore, AAWE could potentially be developed as an environmentally friendly botanical herbicide due to its strong allelopathic effects.


Asunto(s)
Artemisia , Oryza , Alelopatía , Hormonas/metabolismo , Oryza/metabolismo , Fotosíntesis , Especies Reactivas de Oxígeno/metabolismo
20.
Front Plant Sci ; 13: 906725, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35795352

RESUMEN

Artemisia argyi Levl. et Van is an important Asteraceae species with a high medicinal value. There are abundant A. argyi germplasm resources in Asia, especially in China, but the evolutionary relationships of these varieties and the systematic localization of A. argyi in the family Asteraceae are still unclear. In this study, the chloroplast (cp) genomes of 72 A. argyi varieties were systematically analyzed. The 72 varieties originated from 47 regions in China at different longitudes, latitudes and altitudes, and included both wild and cultivated varieties. The A. argyi cp genome was found to be ∼151 kb in size and to contain 114 genes, including 82 protein-coding, 28 tRNA, and 4 rRNA genes. The number of short sequence repeats (SSRs) in A. argyi cp genomes ranged from 35 to 42, and most of them were mononucleotide A/T repeats. A total of 196 polymorphic sites were detected in the cp genomes of the 72 varieties. Phylogenetic analysis demonstrated that the genetic relationship between A. argyi varieties had a weak relationship with their geographical distribution. Furthermore, inverted repeat (IR) boundaries of 10 Artemisia species were found to be significantly different. A sequence divergence analysis of Asteraceae cp genomes showed that the variable regions were mostly located in single-copy (SC) regions and that the coding regions were more conserved than the non-coding regions. A phylogenetic tree was constructed using 43 protein-coding genes common to 67 Asteraceae species. The resulting tree was consistent with the traditional classification system; Artemisia species were clustered into one group, and A. argyi was shown to be closely related to Artemisia lactiflora and Artemisia montana. In summary, this study systematically analyzed the cp genome characteristics of A. argyi and compared cp genomes of Asteraceae species. The results provide valuable information for the definitive identification of A. argyi varieties and for the understanding of the evolutionary relationships between Asteraceae species.

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