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1.
Toxicol Mech Methods ; : 1-8, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39081123

RESUMEN

In medical practice, iodine contrast media are necessary for diagnostic techniques. However, it comes with a potential risk to the patient in the form of allergic reactions. The aim of this research is to study the effects of iodine contrast media on endothelial cells in an in vitro system at various concentrations, specifically investigating their impact on cell viability, cell cycle, and apoptosis in the treated cells within the field of diagnostic radiology. Our results showed that in iodine contrast media, when the concentration was within the range of 2.5-50 mgI/ml, cell viability decreased by 50%. Conversely, exposure to ioversol at concentrations between 12.5 and 50.0 mgI/ml resulted in a notable increase in the percentage of total apoptotic cells, including both early and late apoptosis. In conclusion, our in vitro investigation sheds light on the effect of iodinated contrast media on endothelial cell viability, cell cycle progression, and apoptosis. These findings contribute valuable insights to ensure the safety of their use, aligning with guidelines in radiological procedures. Further research and adherence to established guidelines are crucial for refining our understanding and promoting the safe application of iodinated contrast media in the field of radiology.

2.
Metallomics ; 16(7)2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38936837

RESUMEN

Ferric-tannic nanoparticles (FTs) are now considered to be new pharmaceuticals appropriate for the prevention of brain aging and related diseases. We have previously shown that FTs could activate axon guidance pathways and cellular clearance functioning in neuronal cell lines. Herein, we further investigated whether FTs could activate the two coordinated neuronal functions of axon guidance and synaptic function in rat brains and neuronal cell lines. A single intravenous injection of a safe dose of FTs has been shown to activate a protein expression of axon attractant Netrin-1 and neurotransmitter receptor GABRA4 in the cerebral cortexes of male Wistar rats. According to RNA-seq with targeted analysis, axon guidance and synapses have been enriched and Ephrin membered genes have been identified as coordinating a network of genes for such processes. In vitro, as expected, FTs are also found to activate axon guidance markers and promote neuronal tubes in neuronal cell lines. At the same time, pre-synaptic markers (synaptophysin), post-synaptic markers (synapsin), and GABRA4 neurotransmitter receptors have been found to be activated by FTs. Interestingly, synaptophysin has been found to localize along the promoted neuronal tubes, suggesting that enhanced axon guidance is associated with the formation and transportation of pre-synaptic vesicles. Preliminarily, repeated injection of FTs into adult rats every 3 days for 10 times could enhance an expression of synaptophysin in the cerebral cortex, as compared to control rats. This work demonstrates that FTs can be used for activating brain function associated with axon guidance and synaptic function.


Asunto(s)
Orientación del Axón , Ratas Wistar , Sinapsis , Animales , Masculino , Ratas , Sinapsis/metabolismo , Encéfalo/metabolismo , Sinaptofisina/metabolismo , Compuestos Férricos/metabolismo , Receptores de GABA-A/metabolismo , Netrina-1/metabolismo , Nanopartículas/química , Biomarcadores/metabolismo , Neuronas/metabolismo , Axones/metabolismo
3.
Arch Biochem Biophys ; 756: 110020, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692471

RESUMEN

Iron deposits in the brain are a natural consequence of aging. Iron accumulation, especially in the form of labile iron, can trigger a cascade of adverse effects, eventually leading to neurodegeneration and cognitive decline. Aging also increases the dysfunction of cellular proteostasis. The question of whether iron alters proteostasis is now being pondered. Herein, we investigated the effect of ferric citrate, considered as labile iron, on various aspects of proteostasis of neuronal cell lines, and also established an animal model having a labile iron diet in order to evaluate proteostasis alteration in the brain along with behavioral effects. According to an in vitro study, labile iron was found to activate lysosome formation but inhibits lysosomal clearance function. Furthermore, the presence of labile iron can alter autophagic flux and can also induce the accumulation of protein aggregates. RNA-sequencing analysis further reveals the upregulation of various terms related to proteostasis along with neurodegenerative disease-related terms. According to an in vivo study, a labile iron-rich diet does not induce iron overload conditions and was not detrimental to the behavior of male Wistar rats. However, an iron-rich diet can promote iron accumulation in a region-dependent manner. By staining for autophagic markers and misfolding proteins in the cerebral cortex and hippocampus, an iron-rich diet was actually found to alter autophagy and induce an accumulation of misfolding proteins. These findings emphasize the importance of labile iron on brain cell proteostasis, which could be implicated in developing of neurological diseases.


Asunto(s)
Encéfalo , Hierro , Enfermedades Neurodegenerativas , Proteostasis , Ratas Wistar , Animales , Proteostasis/efectos de los fármacos , Enfermedades Neurodegenerativas/metabolismo , Masculino , Hierro/metabolismo , Ratas , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Autofagia/efectos de los fármacos , Humanos , Lisosomas/metabolismo
4.
Sci Rep ; 14(1): 2348, 2024 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287075

RESUMEN

Acacetin, one of the flavonoid compounds, is a natural product found in various plants, including Silver birch, and Damiana. Previous studies showed that acacetin has anti-cancer effects on many kinds of cancer cells, however, the role of and the mechanisms of actions of acacetin on non-small cell lung cancer (NSCLC) cells is still not fully understood. Herein, we found that, in vitro, acacetin inhibited the proliferation, invasion, and migration of NSCLC cells, A549 and H460, in a dose-dependent manner. Meanwhile, flow cytometry assay results showed that acacetin induced G2/M phase cell cycle arrest, and apoptosis of NSCLC cells. In vivo, acacetin suppressed tumor formation of A549-xenografted nude mice model with no obvious toxicities. Western blotting results showed that the protein levels of cell cycle-related proteins cyclin B1, cyclin D, and anti-apoptotic protein Bcl-2 had decreased, while the apoptosis-related protein Bak had increased both in NSCLC cells and in A549-xenografted tumor tissues. For investigating the molecular mechanism behind the biological effects of acacetin on NSCLC, we found that acacetin induced the expression levels of tumor suppressor p53 both in vitro and in vivo. MicroRNA, miR-34a, the direct target of p53, has been shown anti-NSCLC proliferation effects by suppressing the expression of its target gene programmed death ligand 1 (PD-L1). We found that acacetin upregulated the expression levels of miR-34a, and downregulated the expression levels of PD-L1 of NSCLC cells in vitro and of tumors in vivo. In vitro, knockdown p53 expression by siRNAs reversed the induction effects of acacetin on miR34a expression and abolished the inhibitory activity of acacetin on NSCLC cell proliferation. Furthermore, using agomir and antagomir to overexpress and suppress the expression miR-34a in NSCLC cells was also examined. We found that miR-34a agomir showed similar effects as acacetin on A549 cells, while miR-34a antagomir could partially or completely reverse acacetin's effects on A549 cells. In vivo, intratumor injection of miR-34a antagomir could drastically suppress the anti-tumor formation effects of acacetin in A549-xenografted nude mice. Overall, our results showed that acacetin inhibits cell proliferation and induces cell apoptosis of NSCLC cells by regulating miR-34a.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Flavonas , Neoplasias Pulmonares , MicroARNs , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antígeno B7-H1/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ratones Desnudos , Antagomirs/farmacología , Línea Celular Tumoral , MicroARNs/metabolismo , Proliferación Celular , Proteínas de Ciclo Celular/metabolismo , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica
5.
Metallomics ; 16(1)2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38148121

RESUMEN

Iron dyshomeostasis is involved in many neurological disorders, particularly neurodegenerative diseases where iron accumulates in various brain regions. Identifying mechanisms of iron transport in the brain is crucial for understanding the role of iron in healthy and pathological states. In neurons, it has been suggested that iron can be transported by the axon to different brain regions in the form of labile iron; a pool of reactive and exchangeable intracellular iron. Here we report a novel approach to imaging labile ferrous iron, Fe(II), in live primary hippocampal neurons using confocal and TauSTED (stimulated emission depletion) microscopy. TauSTED is based on super-resolution STED nanoscopy, which combines high spatial resolution imaging (<40 nm) with fluorescence lifetime information, thus reducing background noise and improving image quality. We applied TauSTED imaging utilizing biotracker FerroFarRed Fe(II) and found that labile iron was present as submicrometric puncta in dendrites and axons. Some of these iron-rich structures are mobile and move along neuritic pathways, arguing for a labile iron transport mechanism in neurons. This super-resolution imaging approach offers a new perspective for studying the dynamic mechanisms of axonal and dendritic transport of iron at high spatial resolution in living neurons. In addition, this methodology could be transposed to the imaging of other fluorescent metal sensors.


Asunto(s)
Hierro , Neuronas , Microscopía Fluorescente/métodos , Colorantes Fluorescentes/química , Hipocampo , Compuestos Ferrosos
6.
Toxicol Mech Methods ; 33(8): 667-674, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37403420

RESUMEN

Iodine contrast agents are essential for diagnostic purposes in radiology and have significant medical benefits. However, they pose a risk of causing allergic reactions or adverse cellular effects. In this study, we examine the in vitro effects of iodine contrast agents (Iopamiro 370, Ultravist 370, Visipaque 320, and Optiray 350) on cellular functions of human peripheral blood mononuclear. The findings reveal that a concentration of 50 mgI/ml of iodine contrast agents causes a 50% reduction in cell viability, but lower concentrations of 2.5, 5.0, and 10.0 mgI/ml do not affect the cell cycle. Furthermore, the contrast agents decrease oxidative stress levels in cells. In conclusion, this study demonstrates that iodine contrast agents can be used safely in appropriate concentrations for diagnostic purposes without affecting the cell cycle and preventing oxidative stress on normal cells. The insights gained from this study could aid in the development of diagnostic contrast agents in the future of medicine.


Asunto(s)
Medios de Contraste , Yodo , Humanos , Medios de Contraste/toxicidad , Supervivencia Celular , Leucocitos Mononucleares , Yodo/toxicidad , Ciclo Celular
7.
Anal Chem ; 95(27): 10241-10248, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37358189

RESUMEN

Herein, we present molecular nanoparticles of ferric-tannic complexes (so called ferric-tannic nanoparticles, FT NPs) used to enhance the MRI signal in the early stage of hepatocarcinoma. FT NPs were found to accumulate in the hepatic parenchyma without tumor nodules of Wistar rats in which hepatocarcinogenicity had been induced using diethylnitrosamine (DEN). The MRI enhancement and accumulation of FT NPs were clearly observed in the early phase of hepatocarcinogenicity, which was possibly modulated by various solute carrier family members present in the entire hepatic parenchyma of the DEN-induced rats. These findings suggest that MRI with FT NPs is promising for the assessment of the early stage of hepatocarcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Ratas , Animales , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Carcinogénesis , Ratas Wistar , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/diagnóstico por imagen , Imagen por Resonancia Magnética , Hierro
8.
Polymers (Basel) ; 15(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36679309

RESUMEN

Radiation protection in radiology is important because radiation may cause harm to the human body. The equipment for radiation protection is essential to ensure safe operations. Currently, there is widespread research on lead-free radiation shielding material. The aim of this research was to study lead-free material containing epoxy and iodine contrast media that was easy to form, low in cost, and environmentally friendly. The results showed that 2-cm material thickness with a concentration of 20% iodine had the greatest properties of radiation attenuate in the peak potential applied at technique 60-120 kVp, but the structure and strength of the shielding materials were decreased in accordance with increasing concentrations of iodine contrast media. It can be concluded that the lead-free epoxy radiation-shielding materials are able to absorb radiation at energy levels of 60-120 kVp. However, with improvement on homogeneity in the future, it could be used as a refractory shielding material in the radiology department.

9.
Cancer Med ; 12(4): 4993-5008, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36226375

RESUMEN

BACKGROUND: Regulatory T cells (Tregs) have an important role in accelerating the immunosuppression of tumor. Tregs regulation is a hopeful strategy to improve the dismal prognosis of Esophageal cancer (EC), while its mechanisms have not yet been fully clarified. METHODS: To characterize the role of Tregs in EC, we comprehensively explored its prognostic value, clinical pathology partnership, related biological functions and potential mechanisms at transcriptome level. Through the integrated analysis of GEO and TCGA datasets, we comprehensively evaluated the Tregs infiltration patterns in EC patients. The correlation between Tregs infiltration and genomic characteristics, as well as biological functions were analyzed by a variety of computational algorithms. RESULTS: We observed that Tregs were significantly upregulated in EC and involved in various immune processes. According to TCGA and GEO transcriptional classification schemes, Tregs specific genes were observed to be highly expressed in tumor samples, as well as were closely associated with poor prognosis and worse clinical outcomes. In addition, EC patients can be stratified into high-risk and low-risk immune subgroups according to Tregs/macrophages infiltration level, and the results showed significant differences in tumor development, biological processes and probe gene expression pattern. The multi-variate analysis revealed that the interaction between STAT3 and Foxp3 was a potential prognostic signature of Tregs in EC, especially the modulation effect of STAT3 on Foxp3 expression, which has not been well studied in EC. We also identified that STAT3 and Foxp3 expression presented a high accuracy in predicting Tregs infiltration level in EC patients (AUC: 0.817; 95% CI: 0.756-0.878). CONCLUSIONS: Our results revealed that Tregs have the potential to predict prognosis and tumor deterioration in EC patients. A comprehensive landscape of Tregs regulation mechanisms will help us interpret the immunosuppression of tumor microenvironment (TME) and novel strategies for EC immunotherapy.


Asunto(s)
Neoplasias Esofágicas , Linfocitos T Reguladores , Humanos , Neoplasias Esofágicas/patología , Pronóstico , Factores de Transcripción/metabolismo , Microambiente Tumoral , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
10.
Molecules ; 27(18)2022 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-36144639

RESUMEN

Lung cancer is the second leading cause of cancer-related death worldwide. In recent decades, investigators have found that microRNAs, a group of non-coding RNAs, are abnormally expressed in lung cancer, and play important roles in the initiation and progression of lung cancer. These microRNAs have been used as biomarkers and potential therapeutic targets of lung cancer. Polyphenols are natural and bioactive chemicals that are synthesized by plants, and have promising anticancer effects against several kinds of cancer, including lung cancer. Recent studies identified that polyphenols exert their anticancer effects by regulating the expression levels of microRNAs in lung cancer. Targeting microRNAs using polyphenols may provide a novel strategy for the prevention and treatment of lung cancer. In this review, we reviewed the effects of polyphenols on oncogenic and tumor-suppressive microRNAs in lung cancer. We also reviewed and discussed the potential clinical application of polyphenol-regulated microRNAs in lung cancer treatment.


Asunto(s)
Anticarcinógenos , Neoplasias Pulmonares , MicroARNs , Anticarcinógenos/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevención & control , MicroARNs/metabolismo , Polifenoles/farmacología , Polifenoles/uso terapéutico
11.
Anal Chem ; 94(38): 12960-12970, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-36102901

RESUMEN

Iron-containing drugs can be considered beneficial for noninvasive magnetic resonance imaging (MRI) and induction of essential biochemical processes. Herein, we present a new type of iron-containing drug based on molecular nanoparticles of ferric-tannic complexes (FTs), which could be used to enhance noninvasive brain MRI and modulate brain clearance pathways. Once intravenously administered to healthy Wistar rats, the maximum enhancement of the T1-weighted MRI signal was observed at 0.5 h postinjection, corresponding to their maximum accumulation in the brain. After this time, FTs were rapidly cleared by the brain, which was possibly modulated by organic anion transporters present at the blood-brain barrier. This result describes the "come-and-run" concept of FTs, which could be utilized as a brain-targeting agent for various purposes. Although the "come-and-run" mechanism allows them to have a short half-life in the brain, they remain long enough to activate brain clearance pathways such as autophagy, lysosomal function, and cellular clearance. Therefore, FTs could be considered new clinically translatable pharmaceuticals for brain MRI and the prevention of brain aging and related diseases.


Asunto(s)
Nanopartículas , Transportadores de Anión Orgánico , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Medios de Contraste/química , Compuestos Férricos/química , Hierro/metabolismo , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Transportadores de Anión Orgánico/metabolismo , Ratas , Ratas Wistar
12.
Nanomaterials (Basel) ; 12(7)2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35407158

RESUMEN

Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione S-transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD50 value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.

13.
Nanotheranostics ; 6(2): 195-204, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34976594

RESUMEN

Assessment and enhancement of liver clearance are promising strategies for protection of liver from various liver diseases. Iron-tannic nanoparticles (FTs) were previously considered as imageable autophagic enhancers with biodegradation potential. Herein, we present a new approach for utilizing Iron-tannic nanoparticles (FTs) as a tool for imaging and increasing liver clearance. Pharmacokinetic profiling suggested that FTs were initially found in blood circulation and thereafter were distributed to the liver. By using MR imaging (T1 weighted), maximum MRI signal enhancement was found to occur after 30 minutes post-injection (i.v.) and gradually decreased afterward. Decreasing MRI signal may be due to FTs metabolism by the liver. By assessing imaging-derived pharmacokinetics, we can simply determine the rate constant of liver degradation of FTs. Potentially, we might use this parameter to monitor liver function, where its clearance is of concern. Once functional implication of FTs in liver clearance was investigated, FTs were found to induce hepatocyte autophagy along with activation of lysosomes. Consequently, the hepatocytes were capable of efficiently clearing cellular debris. From these results, it is clear that FTs should be considered as a molecular tool for quantitative MRI-derived liver function assessment, and for enhancing clearance function in liver parenchyma. Hopefully, our findings will pave the way to develop new strategies for non-invasive assessment and enhancement of liver clearance.


Asunto(s)
Hierro , Nanopartículas , Medios de Contraste/farmacocinética , Hierro/metabolismo , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética/métodos
14.
Front Oncol ; 11: 740484, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745960

RESUMEN

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is rising worldwide, and there is limited therapeutic efficacy due to tumor microenvironment heterogeneity and difficulty in early-stage screening. This study aimed to develop and validate a gene set-based signature for early-stage HCC (eHCC) patients and further explored specific marker dysregulation mechanisms as well as immune characteristics. METHODS: We performed an integrated bioinformatics analysis of genomic, transcriptomic, and clinical data with three independent cohorts. We systematically reviewed the crosstalk between specific genes, tumor prognosis, immune characteristics, and biological function in the different pathological stage samples. Univariate and multivariate survival analyses were performed in The Cancer Genome Atlas (TCGA) patients with survival data. Diethylnitrosamine (DEN)-induced HCC in Wistar rats was employed to verify the reliability of the predictions. RESULTS: We identified a Cluster gene that potentially segregates patients with eHCC from non-tumor, through integrated analysis of expression, overall survival, immune cell characteristics, and biology function landscapes. Immune infiltration analysis showed that lower infiltration of specific immune cells may be responsible for significantly worse prognosis in HCC (hazard ratio, 1.691; 95% CI: 1.171-2.441; p = 0.012), such as CD8 Tem and cytotoxic T cells (CTLs) in eHCC. Our results identified that Cluster C1 signature presented a high accuracy in predicting CD8 Tem and CTL immune cells (receiver operating characteristic (ROC) = 0.647) and cancerization (ROC = 0.946) in liver. As a central member of Cluster C1, overexpressed PRKDC was associated with the higher genetic alteration in eHCC than advanced-stage HCC (aHCC), which was also connected to immune cell-related poor prognosis. Finally, the predictive outcome of Cluster C1 and PRKDC alteration in DEN-induced eHCC rats was also confirmed. CONCLUSIONS: As a tumor prognosis-relevant gene set-based signature, Cluster C1 showed an effective approach to predict cancerization of eHCC and its related immune characteristics with considerable clinical value.

15.
Cell Biochem Biophys ; 79(1): 133-139, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33064258

RESUMEN

Herein, we studied the effect of labile iron (ferric chloride) on the progression of liver cancer cells (HepG2.2.15). The iron was found to induce cell proliferation, growth, and migration in both traditional two-dimensional (2D) and three-dimensional cell (3D) culture models. Biophysical and cell cycle determinations also showed the change in functional cellular biophysical features (cell morphology) and cell cycle kinetic during cancer cell growth induced by the labile iron. According to immunofluorescence and the iron uptake inhibition studies, L-type calcium channel was found to plays a role in the iron uptake in the liver cancer cells. This report gives new insights into iron-mediated cancer cell growth and will pave the new way to diagnosis and treatment of liver cancer.


Asunto(s)
Canales de Calcio Tipo L/metabolismo , Hierro/metabolismo , Neoplasias Hepáticas/metabolismo , Transporte Biológico , Biofisica , Calcio/metabolismo , Bloqueadores de los Canales de Calcio , Ciclo Celular , Proliferación Celular , Cloruros , Progresión de la Enfermedad , Compuestos Férricos , Células Hep G2 , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Cinética , Metástasis de la Neoplasia , Transducción de Señal , Sales de Tetrazolio/química , Tiazoles/química
16.
Nanoscale ; 12(11): 6556-6561, 2020 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-32159197

RESUMEN

We herein report a new biological consequence from a unique interaction between nanoparticles of ferric-tannic complexes (Fe-TA NPs) and liver cancer cells (HepG2.2.15). The Fe-TA NPs were found to accumulate into the cells via specific cellular uptake mechanisms and thereafter disturbed cellular autophagy and cellular pH homeostasis, which led the cells to undergo autophagic stress and eventual death. According to biophysical analysis, the cells undergoing autophagic stress were found to lose their capability of attachment, migration, and movement. Similarly, KEGG analysis demonstrated the down-regulation of TGF-beta indicating that the autophagic stress is capable of reducing cancer cell invasion. Therefore, the Fe-TA NPs could be considered beneficial as a new pharmaceutical nanoplatform for liver cancer treatment via induction of autophagic stress.


Asunto(s)
Muerte Celular Autofágica/efectos de los fármacos , Compuestos Férricos , Neoplasias Hepáticas , Nanopartículas , Taninos , Compuestos Férricos/química , Compuestos Férricos/farmacología , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Nanopartículas/química , Nanopartículas/uso terapéutico , Invasividad Neoplásica , Metástasis de la Neoplasia , Taninos/química , Taninos/farmacología
17.
RSC Adv ; 10(58): 35419-35425, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-35515681

RESUMEN

The most challenging part of liver cancer detection is finding it in the very early stages. It has been argued that liver preneoplasia is found at the very earliest stages of liver cancer. The presence of a lesion is closely related to the development of HCC. We report herein a new class of iron-based T1 MRI contrast agents which are nanoparticles of iron-tannic complexes (so-called Fe-TA NPs) that can be used for detecting liver preneoplasia. Preliminary assessment of their toxicity in healthy rats provides suitable imaging dose ranges with acceptable toxicity. In diethylnitrosamine (DEN) induced rats, it is shown that Fe-TA NPs are capable of enhancing MRI signals in rat livers having pre-neoplastic lesions within 60 minutes post-injection. The enhancement efficacy is strongly dependent on the characteristics of pre-neoplastic foci (GST-P+ foci). The highest enhancement was in good correlation with the size of GST-P+ foci and amount of Fe-TA NPs accumulated in the liver, and might be caused by the dysfunction of liver sinusoids along with cellular uptake capability of pre-neoplastic hepatocytes. Our results show that Fe-TA NPs are of great interest to develop as an efficient MRI imaging agent for risk assessment of liver cancer.

18.
ACS Chem Neurosci ; 10(9): 4136-4144, 2019 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-31355625

RESUMEN

Targeting cellular clearance function in brain cells provides new opportunities for the prevention of dementia by clearance of potentially dangerous molecules. Herein, we present a new approach to enhancing neuroactive and neuroprotective activities in a neuronal cell line using ferric-tannic nanoparticles (FTs). Major biological functions mediated by FTs were clearly found to promote neuronal tube growth through the activation of axon guidance pathways. A number of neuronal tubes were found to increase under stimulation of amyloid beta-peptides, oxidative stress, and serum deprivation. The neuronal tubes generated play a role in clearing debris and amyloid beta-peptides. Another key function in cellular clearance mediated by FTs was their capability of inducing autophagy with the activation of lysosomes. Therefore, FTs are a promising new strategy for brain cell protection through the activation of the cellular clearance function. Hopefully, our findings will pave the way for the development of new methods for the prevention and therapy of dementia.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Nanopartículas del Metal , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Humanos , Lisosomas/metabolismo , Neuronas/metabolismo
19.
Eur J Pharm Sci ; 114: 64-73, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29225106

RESUMEN

This report presents the potential utilization of tannic acid (TA) as a natural iron chelator. TA is capable of binding with small ferric complexes without competitive binding with endogenous iron-containing molecules such as ferritin and transferrin. It was observed that the extracellular iron binding of TA resulted in the formation of self-assembled Fe3+-TA complexes, which were then taken up by HepG2 cells via phagocytosis pathway with autophagy-inducing properties. Obviously, TA was found to inhibit iron-induced HepG2 cell growth. However, cellular interactions and biological responses to the treatment were found to depend on availability of iron. Based on the results of the iron efflux experiment, it can be stated that TA has the capability to mobilize iron from cells in the form of assembled Fe3+-TA complexes. Interestingly, TA-mediated cellular iron influx and efflux were successfully monitored via MRI. The results of this study suggest that TA can be used as a molecular tool for chelating and imaging labile iron. This might be a promising approach for prevention and treatment of iron-associated cancer or other iron overload disorders.


Asunto(s)
Quelantes/metabolismo , Cloruros/metabolismo , Compuestos Férricos/metabolismo , Hierro/metabolismo , Taninos/metabolismo , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Quelantes/farmacología , Cloruros/farmacología , Compuestos Férricos/farmacología , Células Hep G2 , Humanos , Hierro/farmacología , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Taninos/farmacología
20.
Biointerphases ; 12(2): 021005, 2017 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-28592112

RESUMEN

Herein, a new magnetic resonance imaging (MRI) agent based on molecular nanoparticles of iron(III)-tannic complexes (Fe-TA NPs) is reported. The paramagnetic and molecularlike Fe-TA NPs were successfully synthesized at room temperature within a few minutes without the use of any toxic agents or expensive equipment. The coordination states of the Fe-TA NPs were pH-dependent. The r1 relaxivity values of the bis-dominated and tris-dominated structures of the Fe-TA NPs were determined to be 6.31 and 5.24 mM-1 s-1, respectively, by using a Philips Achieva 1.5T MRI scanner. The Fe-TA NPs were 177 ± 12 nm in diameter (hydrodynamic size) with a zeta potential value of -28 ± 0.9 mV, dispersing very well in aqueous solution and were highly stable in phosphate buffered saline buffer (pH 7.4) containing competitive ligands and metals. From in vitro studies, it was evident that the Fe-TA NPs exhibited good biocompatibility, with high cellular uptake in HepG2 cells. Clearly, the Fe-TA NPs were found to induce signal enhancement in the T1-weighted image of the HepG2 cells. As a result, it can be stated that the Fe-TA NPs may have the potential for being developed as low-cost and clinically translatable magnetic resonance imaging agents in the near future.


Asunto(s)
Medios de Contraste , Complejos de Coordinación , Hierro , Imagen por Resonancia Magnética/métodos , Nanopartículas , Taninos , Medios de Contraste/química , Medios de Contraste/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Células Hep G2 , Humanos , Hierro/química , Hierro/farmacología , Ensayo de Materiales/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico , Taninos/química , Taninos/farmacología
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