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The precise quantitative analysis using surface-enhanced Raman spectroscopy (SERS) in an uncontrollable environment still faces a significant obstacle due to the poor reproducibility of Raman signals. Herein, we propose a facile method to fabricate a self-calibrating substrate based on a flexible polyvinyl alcohol (PVA) film comprising assemblies of Prussian blue (PB) and Au NPs (PB@Au) for reliable detection. PB cores were coated with an Au shell through simple electrostatic interaction, forming core-shell nanostructure PB@Au assemblies within the PVA film. The outer Au layer provided identical trends in enhancement for both the PB core and neighboring targets while PB cores served as an internal standard (IS) to correct signal fluctuations. The prevention of competitive adsorption on the metal surface between targets and ISs was achieved. The proposed PVA/PB@Au film exhibited enhanced stability of Raman signals after IS correction, resulting in improved spot-to-spot and batch-to-batch reproducibility with significantly reduced standard deviation (RSD) values from 11.42% and 25.02% to 4.43% and 9.39%, respectively. Simultaneously, a higher accuracy in the quantitative analysis of 4-mercaptobenzoic acid (4-MBA) and malachite green (MG) was achieved with fitting coefficient (R2) values improving from 0.9675 and 0.9418 to 0.9974 and 0.9832, respectively. Moreover, the PVA/PB@Au film was successfully applied to detect residual MG in real fish samples. This work opens up an avenue to improve the reproducibility of Raman signals for flexible SERS substrates in the detection of residues under various complex conditions.
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The Chinese hamster ovary (CHO) cell is an epithelial-like cell that produces proteins with post-translational modifications similar to human glycosylation. It is widely used in the production of recombinant therapeutic proteins and monoclonal antibodies. Culturing CHO cells typically requires the addition of a certain proportion of fetal bovine serum (FBS) to maintain cell proliferation and passaging. However, serum is characterized by its complex composition, batch-to-batch variability, high cost, and potential risk of exogenous contaminants such as mycoplasma and viruses, which impact the purity and safety of the synthesized proteins. Therefore, search for serum alternatives and development of serum-free media for CHO-based protein biomanufacturing are of great significance. This review systematically summarizes the application advantages of CHO cells and strategies for high-density expression. It highlights the developmental trends of serum substitutes from human platelet lysates to animal-free extracts and microbial-derived substances and elucidates the mechanisms by which these substitutes enhance CHO cell culture performance and recombinant protein production, aiming to provide theoretical guidance for exploring novel serum alternatives and developing serum-free media for CHO cells.
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Cricetulus , Proteínas Recombinantes , Células CHO , Animales , Medio de Cultivo Libre de Suero , Proteínas Recombinantes/metabolismo , Humanos , Técnicas de Cultivo de Célula/métodos , Cricetinae , Proliferación CelularRESUMEN
Silicosis is a systemic disease with predominantly diffuse fibrosis of the lungs due to prolonged inhalation of free SiO2 dust during the manufacturing process, for which there is no effective treatment. In this study, we used a combined epigenetic and transcriptomic approach to reveal the chromatin-opening features of silicosis and identify the key transcription factor activator protein 1 (AP-1) that responds to silicosis fibrosis. Therapeutic administration of an AP-1 inhibitor inhibits the PI3K/AKT signaling pathway, reduces fibrosis marker proteins, and significantly ameliorates lung fibrosis in a mouse model of silicosis. In addition, it was observed that the expression of Jun and JunB was significantly up-regulated in a TGF-ß1-induced in vitro transdifferentiation model of NIH/3T3 cells, and Co-IP confirmed that a protein complex could be formed between Jun and JunB. Mechanistically, silencing of Jun and JunB expression reversed the activation of the PI3K/AKT signaling pathway and the upregulation of fibrosis marker proteins in NIH/3 T3 cells after TGF-ß1 stimulation. Taken together, Jun/JunB is expected to be a potential therapeutic target for silicosis fibrosis.
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Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.
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Cobre , Silicosis , Humanos , Animales , Ratones , Cobre/toxicidad , Silicosis/genética , Apoptosis , Biología Computacional , Modelos Animales de Enfermedad , ARN Mensajero , Dióxido de Silicio/toxicidadRESUMEN
Long-term exposure to inhalable silica particles may lead to severe systemic pulmonary disease, such as silicosis. Exosomes have been demonstrated to dominate the pathogenesis of silicosis, but the underlying mechanisms remain unclear. Therefore, this study aimed to explore the roles of exosomes by transmitting miR-107, which has been linked to the toxic pulmonary effects of silica particles. We found that miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in exosomes extracted from the serum of patients with silicosis. Notably, an increase in miR-107 in serum exosomes and lung tissue was observed in the experimental silicosis mouse model, while the inhibition of miR-107 reduced pulmonary fibrosis. Moreover, exosomes helped the migration of miR-107 from macrophages to lung fibroblasts, triggering the transdifferentiation of cell phenotypes. Further experiments demonstrated that miR-107 targets CDK6 and suppresses the expression of retinoblastoma protein phosphorylation and E2F1, resulting in cell-cycle arrest. Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets.
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Exosomas , MicroARNs , Fibrosis Pulmonar , Dióxido de Silicio , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Animales , Dióxido de Silicio/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Ratones , Humanos , Silicosis/metabolismo , Silicosis/patología , Silicosis/genética , Silicosis/etiología , Comunicación Celular , Masculino , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Macrófagos/metabolismo , Pulmón/patología , Pulmón/metabolismoRESUMEN
Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.
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Manganeso , Linfocitos T , Ratas , Animales , Manganeso/toxicidad , Inmunoglobulina M , Inmunoglobulina G , BiomarcadoresRESUMEN
Mn (Manganese, Mn) is an essential trace element involved in various biological processes such as the regulation of immune, nervous and digestive system functions. However, excessive Mn exposure can lead to immune damage. Occupational workers in cement and ferroalloy manufacturing and other related industries are exposed to low levels of Mn for a long time. Mn exposure is one of the important occupational hazards, but the research on the effect of Mn on the immune system of the occupational population is not complete, and there is no reliable biomarker. Therefore, this study aimed to evaluate the immunotoxicity of Mn from the soluble immune checkpoint TIM-3 (T-cell immunoglobulin and mucin containing protein 3, TIM-3) and complement C3. A total of 144 Mn-exposed workers were recruited from a bus manufacturing company and a railroad company in Henan Province. An inductively coupled plasma mass spectrometer was used to detect the concentration of RBC Mn (Red blood cell Mn, RBC Mn), and ELISA kits were used to detect serum complement C3 and TIM-3. Finally, the subjects were statistically analyzed by dividing them into low and high Mn groups based on the median RBC Mn concentration. We found that Mn exposure resulted in elevated serum TIM-3 expression and decreased complement C3 expression in workers; that serum TIM-3 and complement C3 expression showed a dose-response relationship with RBC Mn; and that the mediating effect of complement C3 between RBC Mn and TIM-3 was found to be significant. The above findings indicate that this study has a preliminary understanding of the effect of Mn exposure on the immune system of the occupational population exposed to Mn, and complement C3 and TIM-3 may be biomarkers of Mn exposure, which may provide clues for the prevention and control of Mn occupational hazards.
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Complemento C3 , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Manganeso/toxicidad , BiomarcadoresRESUMEN
Silicosis, a disease characterized by diffuse fibrosis of the lung tissue, is caused by long-term inhalation of free silica (SiO2) dust in the occupational environment and is currently the most serious occupational diseases of pneumoconiosis. Several studies have suggested that alveolar type â ¡ epithelial cells (AEC â ¡) undergo epithelial-mesenchymal transition (EMT) as one of the crucial components of silicosis in lung fibroblasts. A2aR can play a critical regulatory role in fibrosis-related diseases by modulating the Wnt/ß-catenin pathway, but its function in the EMT process of silicosis has not been explained. In this study, an EMT model of A549 cells was established. The results revealed that A2aR expression is reduced in the EMT model. Furthermore, activation of A2aR or suppression of the Wnt/ß-catenin pathway reversed the EMT process, while the opposite result was obtained by inhibiting A2aR. In addition, activation of A2aR in a mouse silicosis model inhibited the Wnt/ß-catenin pathway and ameliorated the extent of silica-induced lung fibrosis in mice. To sum up, we uncovered that A2aR inhibits fibrosis and the EMT process in silicosis by regulating the Wnt/ß-catenin pathway. Our study can provide an experimental basis for elucidating the role of A2aR in the development of silicosis and offer new ideas for further exploration of interventions for silicosis.
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Transición Epitelial-Mesenquimal , Fibrosis Pulmonar , Receptor de Adenosina A2A , Silicosis , beta Catenina , Animales , Ratones , beta Catenina/genética , beta Catenina/metabolismo , Dióxido de Silicio/toxicidad , Silicosis/metabolismo , Silicosis/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Vía de Señalización Wnt , Receptor de Adenosina A2A/genética , Receptor de Adenosina A2A/metabolismo , Agonistas del Receptor de Adenosina A2/farmacologíaRESUMEN
Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6.
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Exosomas , MicroARNs , Fibrosis Pulmonar , Dióxido de Silicio , Silicosis , Animales , Ratones , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Dióxido de Silicio/toxicidad , Silicosis/genética , Silicosis/patología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Exosomas/genética , Exosomas/metabolismoRESUMEN
Epithelial-mesenchymal transdifferentiation of alveolar type â ¡ epithelial cells is a vital source of pulmonary myofibroblasts, and myofibroblasts formation is recognized as an important phase in the pathological process of silicosis. miR-30c-5p has been determined to be relevant in the activation of the epithelial-mesenchymal transition (EMT) in numerous disease processes. However, elucidating the role played by miR-30c-5p in the silicosis-associated EMT process remains a great challenge. In this work, based on the establishment of mouse silicosis and A549 cells EMT models, miR-30c-5p was interfered with in vivo and in vitro models to reveal its effects on EMT and autophagy. Moreover, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), connective tissue growth factor (CTGF), autophagy-related gene 5 (ATG5), and autophagy were further interfered with in the A549 cells models to uncover the possible molecular mechanism through which miR-30c-5p inhibits silicosis associated EMT. The results demonstrated the targeted binding of miR-30c-5p to CTGF, ATG5, and MALAT1, and showed that miR-30c-5p could prevent EMT in lung epithelial cells by acting on CTGF and ATG5-associated autophagy, thereby inhibiting the silicosis fibrosis process. Furthermore, we also found that lncRNA MALAT1 might competitively absorb miR-30c-5p and affect the EMT of lung epithelial cells. In a word, interfering with miR-30c-5p and its related molecules (MALAT1, CTGF, and ATG5-associated autophagy) may provide a reference point for the application of silicosis intervention-related targets.
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Células Epiteliales Alveolares , Proteína 5 Relacionada con la Autofagia , Factor de Crecimiento del Tejido Conjuntivo , Transición Epitelial-Mesenquimal , MicroARNs , ARN Largo no Codificante , Silicosis , Animales , Ratones , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Proteína 5 Relacionada con la Autofagia/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Dióxido de Silicio/toxicidad , Silicosis/genética , Silicosis/metabolismoRESUMEN
In this review, we report the recent advances of SERS in fungi, bacteria, and viruses. Firstly, we briefly introduce the advantage of SERS over fluorescence on virus identification and detection. Secondly, we review the feasibility analysis of Raman/SERS spectrum analysis, identification, and fungal detection on SERS substrates of various nanostructures with a signal amplification mechanism. Thirdly, we focus on SERS spectra for nucleic acid, pathogens for the detection of viruses and bacteria, and furthermore introduce SERS-based microdevices, including SERS-based microfluidic devices, and three-dimensional nanostructured plasmonic substrates.
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BACKGROUND: Excessive accumulation of extracellular matrix is a key feature of pulmonary fibrosis (PF), and myofibroblasts are the main producers of extracellular matrix. Fibroblasts are the major source of myofibroblasts, but the mechanisms of transdifferentiation are unclear. METHODS: In vitro, transforming growth factor-ß1 was used to induce NIH-3T3 cell transdifferentiation. DMOG was used to increase hypoxia-inducible factor-1α subunit (HIF-1α) expression. KC7F2 and siRNA decreased HIF-1α expression. In vivo, silica particles were used to induce PF in C57BL/6N mice, and KC7F2 was used to reduce HIF-1α expression in C57BL/6N mice. Western blot was used to detect the expression of collagen type 1 alpha 1(COL1A1), α-smooth muscle actin (α-SMA), SMAD family member (SAMD) 3, Phospho-SMAD3 (PSMAD3), and HIF-1α. PCR was used to detect the expression of COL1A1, α-SMA, and HIF-1α. Immunohistochemistry was used to detect the expression of COL1A1 and HIF-1α. RESULTS: In vitro, compared to the control group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression were elevated in the DMOG group, and COL1A1, α-SMA, PSMAD3, and HIF-1α expression were decreased in the KC7F2 group and siRNA group. Compared to the DMOG group, COL1A1, α-SMA, and PSMAD3 expression were decreased in the DMOG + SIS3 group. In vivo, compared to the saline group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression were increased in the pulmonary tissue of C57BL/6N mice in the silica group. Compared to the silica group, COL1A1, α-SMA, PSMAD3, and HIF-1α expression and the degree of PF were decreased in the silica + KC7F2 group. CONCLUSION: Inhibition of HIF-1α reduced α-SMA, decreased COL1A1 expression, and attenuated the degree of PF in C57BL/6N mice. Therefore, HIF-1α may be a new target for the treatment of silica-induced PF.
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Fibrosis Pulmonar , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , ARN Interferente Pequeño/genética , Dióxido de Silicio/toxicidadRESUMEN
The main clinical manifestations are pulmonary fibrosis, silicosis, is one of the most common types of pneumoconiosis, and its pathogenesis is still unclear. The proliferation and transdifferentiation of fibroblasts are considered to be the key link leading to pulmonary fibrosis. Type II alveolar epithelial cells can be transformed into lung fibroblasts through epithelial-mesenchymal transition (EMT) to promote lung fibrosis. Involved in the EMT process of a variety of cancers, lncRNA UCA1 (UCA1) has been shown to competitively adsorb miR-204-5p, and play an effect on the downstream target gene E-box binding zinc finger protein 1 (ZEB1), thereby promoting EMT to facilitate the invasion and migration of cancer cells. This is an important potential intervention target that affects the process of EMT, but it has not been reported in the study of EMT related to silicosis. Therefore, this study established a SiO2 dust-treated mouse silicosis model and an in vitro EMT model of A549 cells to observe the changes and effects of UCA1 and miR-204-5p, and intervene on the two respectively. The results showed that the EMT process existed in the aforementioned models, while UCA1 was upregulated in the in vitro model. Double luciferase reporter assay demonstrated the targeted binding of UCA1 and miR-204-5p. Silencing UCA1 can up-regulate the expression of miR-204-5p and reduce the level of ZEB1, thus inhibiting EMT process, while intervention of miR-204-5p can change the level of ZEB1 and regulate EMT. Therefore, UCA1 may release its target gene ZEB1 through competitive adsorption of miR-204-5p to regulate EMT process.
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MicroARNs , Fibrosis Pulmonar , ARN Largo no Codificante , Silicosis , Células A549 , Adsorción , Animales , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pulmón/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Dióxido de Silicio/metabolismo , Silicosis/genética , Silicosis/patología , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismoRESUMEN
Silicosis is a systemic disease characterized by diffuse fibrosis of lung tissue. However, its pathogenesis has not been fully elucidated. Previous studies have demonstrated that there is a close relationship between EMT and pulmonary fibrosis. However, LncRNA XIST and miR-101-3p regulate the expression of ZEB1 which is a key transcription factor in the process of EMT through competitive endogenous RNA, thus affecting the process of EMT has not been reported. In this work, an experimental silicosis mouse model and cell model of TGF-ß1 stimulated lung epithelial cells (A549) for 48 h are established to investigate the biological effects of LncRNA XIST/ miR-101-3p/ZEB1 axis in the EMT process. The results reveal that LncRNA XIST and ZEB1 are up-regulated while the miR-101-3p expression is down-regulated in vivo and vitro models. Furthermore, the knockdown of LncRNA XIST prevents the EMT process and the inhibition of miR-101-3p markedly promotes EMT stimulated by TGF-ß1. Moreover, the results also illustrate that LncRNA XIST is mainly localized in the cytoplasm used FISH and possesses binding site with miR-101-3p which was identified as the target of ZEB1 used bioinformatics prediction website and Dual-luciferase reporter assay. The above demonstrated that LncRNA-XIST regulates ZEB1 by directly sponging miR-101-3p. To sum up, we uncovered that the up-regulated LncRNA XIST can modulate miR-101-3p and then up-regulate the expression of ZEB1, thus promoting the EMT process of alveolar epithelial cells in the process of silicosis-related pulmonary fibrosis EMT. Our study provides a new research idea for related targets of silicosis treatment.
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MicroARNs , ARN Largo no Codificante , Silicosis , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Células A549 , Animales , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Humanos , Ratones , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Silicosis/genéticaRESUMEN
Understanding the exact localization of nanoparticles within cell is of particular importance for rational design of high-effective nanomedicines. In the present study, direct stochastic optical reconstruction microscopy (dSTORM) is employed to elucidate the precise localization of nanoparticles within cells owing to its superiority of nanometric resolution, multicolour ability and minimal invasiveness. The localization of the Cy5 labelled mesoporous silica nanoparticles (MSNs-Cy5) in MCF-7 cells are monitored by dSTORM and conventional fluorescence microscopy, respectively. The dSTORM images demonstrate much higher spatial resolution for locating MSNs-Cy5 within cells compared to that of the conventional fluorescence images. Moreover, the distribution of MSNs-Cy5 within three cell lines over time are obtained. For the MCF-7 and HeLa cells, MSNs-Cy5 nanoparticles distribute nearly all around the cytoplasm after 5 h incubation. In contrast, MSNs-Cy5 nanoparticles within NIH 3T3 cells are quite different that they are found to be either attached to or embedded into cell membranes, without penetrating into the cytoplasm. Overall, we provide a practical method to reveal the in situ precise imaging of nanoparticles in cells with nanometric resolution precision. This method may open up new opportunities for organelle-specific targeting drug delivery to achieve maximum therapeutic benefit.
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Nanopartículas , Dióxido de Silicio , Animales , Sistemas de Liberación de Medicamentos/métodos , Células HeLa , Humanos , Ratones , Microscopía Fluorescente/métodos , PorosidadRESUMEN
Ferroptosis is a mode of cell death dependent on iron ions, which is mainly induced by the decrease of the biological activity of glutathione peroxidase or the accumulation of lipid peroxidation and reactive oxygen species (ROS). It is significantly different from autophagy and other forms of cell death in terms of cell morphology and biochemistry. The exact mechanisms of ferroptosis are not clear. More and more studies have shown that various tumor diseases and nervous system diseases are closely related to ferroptosis. The occurrence and development of related diseases can be tolerated by stimulating or inhibiting the occurrence of ferroptosis. Therefore, ferroptosis has occupied a very important position in recent years. This article reviews the discovery process, characteristics, mechanisms, inducers, inhibitors of ferroptosis and its related clinical applications to lay a foundation for follow-up researchers to study ferroptosis and provide some reference value.
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Autofagia , Ferroptosis , Hierro/metabolismo , Neoplasias/patología , Enfermedades del Sistema Nervioso/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Humanos , Neoplasias/metabolismo , Enfermedades del Sistema Nervioso/metabolismoRESUMEN
Organic-inorganic hybrid materials have been considered to be promising carriers or immobilization matrixes for biomolecules due to their high efficiency and significantly enhanced activities and stabilities of biomolecules. Here, the well-defined dopamine/calcium phosphate organic-inorganic hybrids (DACaPMFs) are fabricated via one-pot dopamine-mediated biomineralization, and their structure and properties are also characterized. Direct stochastic optical reconstruction microscopy (dSTORM) is first used to probe the distribution of organic components in these hybrids. Combined with spectroscopic data, the direct observation of dopamine in the hybrids helps to understand the formation of a physical chemistry mechanism of the biomineralization. The obtained DACaPMFs with multiple-level pores allow the loading of doxorubicin with a high loading efficiency and a pH-responsive property. Furthermore, thrombin is entrapped by the hybrids to prove the controlled release. It is expected that such organic-inorganic hybrid materials may hold great promise for application in drug delivery as well as scaffold materials in bone tissue engineering and hemostatic material.
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Fosfatos de Calcio/química , Dopamina/química , Biomineralización , Sistemas de Liberación de Medicamentos , Estructura Molecular , Tamaño de la PartículaRESUMEN
HYPOTHESIS: In view of the photothermal effect of polydopamine (PDA) nanoparticles and their internal D-π-D structures during assembly, the two-photon excited properties of PDA were studied toward the biomedical application. Further, the PDA molecules were coordinated with Mn2+ and the assembled nanoparticles were covered by cancer cell membranes, the complex system could be used directly for the treatment of cancer with photothermal and chemodynamic therapy. EXPERIMENTS: The two-photon excited PDA-Mn2+ nanoparticles were used for the photothermal therapy combined with chemodynamic therapy. The complexes were coated with cancer cell membranes in order to enhance the tumor homologous efficiency. Multi-modal bioimaging and anti-tumor detections were carried out both in vitro and in vivo. FINDINGS: PDA nanoparticles were demonstrated to have both good two-photon excited fluorescence and photothermal efficiency. The assembled nanoparticles modified with Mn2+ and cancer cell membranes have an obvious targeting and synergetic anti-cancer efficiency. The system creates a simple way for a precise operation with multi-modal imaging function.
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Nanopartículas , Neoplasias , Membrana Celular , Indoles , Neoplasias/tratamiento farmacológico , Fototerapia , Terapia Fototérmica , PolímerosRESUMEN
HYPOTHESIS: Crystalline self-assemblies of diphenylalanine (FF) are since long back considered to be related to Alzheimer's disease. An improved understanding of the mechanism behind the formation of such structures can lead to strategies for investigating the dynamic processes of assembly and disassembly of FF. EXPERIMENT: The assembly, disassembly and reassembly of FF crystals are influenced by the solvent composition and can be triggered by evaporation of solvent. In this work these processes are directly monitored, and the structures obtained are analyzed. FINDINGS: The role of the solvent for assembly, disassembly and reassembly of diphenylalanine crystals has been demonstrated. The initial crystal structure formed via self-assembly of FF monomers can be transformed into needle-like crystals and further to hollow hexagonal microtubes through evaporation of the solvent. It is shown that all the assembly-disassembly processes are spontaneous and driven by thermodynamics. It is also found that some of the crystalline structures exhibit optical waveguiding properties.