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BACKGROUND: Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. METHODS: Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function. RESULTS: miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells. CONCLUSIONS: Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.
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Biomarcadores , Diabetes Mellitus , Exosomas , MicroARNs , Animales , Humanos , Ratones , Biomarcadores/metabolismo , Diabetes Mellitus/metabolismo , Células Endoteliales/metabolismo , Exosomas/genética , Exosomas/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Hibridación Fluorescente in Situ , MicroARNs/metabolismoRESUMEN
The design of efficient, stable and cost-effective electrocatalysts for the hydrogen evolution reaction holds substantial significance in water electrolysis, but it remains challenging. Tremella-like nickel-molybdenum bimetal phosphide encapsulated cobalt phosphide (NiMoP/CoP) with hierarchical architectures has been effectively synthesized on nickel foam (NF) via a straightforward hydrothermal followed by low-temperature phosphating method. Based on the unique structural benefits, it significantly increases the number of redox active centers, enhances the electrical conductivity of materials, and diminishes the ion diffusion path lengths, thereby promoting efficient electrolyte penetration and reducing the inherent resistance. The as-obtained NiMoP/CoP/NF electrocatalyst exhibited remarkable catalytic activity with an ultralow overpotential of 38 mV (10 mA cm-2) and low Tafel slope of 83 mV dec-1. The straightforward synthesis process and exceptional electrocatalytic properties of NiMoP/CoP/NF demonstrate great potential for the HER to replace the precious metal catalyst.
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BACKGROUND: As a chronic skin disease, psoriasis often affects the physical, psychological and social status of the patient, which in turn impacts on their experience of illness and needs. However, there is no review of qualitative research that integrates and analyses the experiences and needs of these three influences from a holistic perspective. METHODS: This review follows the ENTREQ guidelines. Six English databases (JBI, Cochrane Library, PubMed, PsyINFO, CINAHL and Embase) and three Chinese databases (CNKI, VIP and Wanfang) were searched from January 2012 to October 2022. Literature was included if it was relevant to the experience of illness and caring needs of patients with psoriasis. The JBI-QARI was used to rate the quality of included studies. RESULTS: Eleven studies were included in the meta-synthesis. Four analytical themes were identified for analysis: physical challenges, psychological discomfort, social phenomena and caring needs. CONCLUSIONS: The combined physical, psychological and social effects of psoriasis and the consequent caring needs should be emphasised. Health professionals, including doctors and nurses, should be aware of the multiple changes in patients and their coping strategies, provide information about psoriasis, monitor and follow-up regularly over time and obtain feedback to inform further treatment and care so as to develop high-quality therapeutic interventions to help and guide patients with their coping strategies. RELEVANCE TO CLINICAL PRACTICE: These findings describe the physical, psychological and social experiences of illness and caring needs of patients with psoriasis. Healthcare professionals should be more aware of patients' easily overlooked psychological and social distress, providing prompt attention and recognition of patients' experiences and needs, offering relevant assistance and support and enhancing daily, regular follow-up to help them improve their understanding of and ability to manage their illness. NO PATIENT OR PUBLIC CONTRIBUTION: This is a meta-synthesis without direct patient involvement.
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Psoriasis , Investigación Cualitativa , Psoriasis/psicología , Psoriasis/enfermería , Humanos , Adaptación Psicológica , Femenino , Masculino , Adulto , Persona de Mediana EdadRESUMEN
The preparation of an electrocatalyst for the oxygen evolution reaction (OER) with high catalytic activity, good long-term durability and rapid reaction kinetics through interface engineering is of great significance. Herein, we have developed a bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel (FeNiS@GA), which serves as an efficient electrocatalyst for OER, by a one-step hydrothermal method. Profiting from the synergy of the FeNiS particle cluster with high capacitance and GA with its three-dimensional porous nanostructure, FeNiS@GA shows a high specific surface area, large pore volume, low contact resistance, and decreases the electron and ion transport routes. FeNiS@GA exhibits outstanding OER activity (when the current density is 50 mA cm-2, the overpotential is 341 mV), low Tafel slope (63.87 mV dec-1) and remarkable stability in alkaline solutions, outperforming FeNiS, NiS@GA, FeS@GA and RuO2. Due to its simple synthesis process and excellent electrocatalytic performance, FeNiS@GA shows great potential to replace noble metal-based catalysts in practical applications.
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Efficient non-noble metal bifunctional electrocatalysts can increase the conversion rate of electric energy in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, a ball & sheet MoS2/Ni3S2 composite with wide-layer-spacing and high 1T-rich MoS2 is assembled on nickel foam (NF) via a two-step solvothermal method with polymeric sulfur (S-r-DIB) as the sulfur source. The obtained material serves as both the cathode and the anode toward overall water splitting in an alkaline electrolyte. The results proved that the interpenetration of MoS2/Ni3S2-p with a ball and sheet structure increased the material active surface area and exposed more catalytic active sites, which contributed to the penetration of solution and the transfer of charge/hydrion. Meanwhile, two different semiconductors of MoS2 and Ni3S2 along with the presence of ample active sulfur edge sites and few-layer, wide-layer-spacing structures of MoS2 lead to an outstanding electrocatalytic activity. In particular, the electrodes of MoS2/Ni3S2-p only need a battery voltage of 1.55 V at 10 mA cm-2. The bifunctional electrocatalyst MoS2/Ni3S2-p also shows excellent stability at large current densities during the electrochemical test.
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Non-coding RNAs have been shown to play vital roles in muscle development. However, the biological roles of long non-coding natural antisense transcripts, antisense lncRNAs (ASlncRNAs), are largely unknown in embryonic muscle development. Here, we identified a total of 466 ASlncRNAs in the longissimus dorsi muscle. And 48 differentially expressed ASlncRNAs were identified based on pairwise comparisons (P < 0.05), sixteen of which were validated by qPCR. Additionally, 466 ASlncRNAs were predicted to target 335 protein coding genes based on complementary base-pairing. Enrichment analysis suggests that ASlncRNAs may be involved in muscle development by negatively regulating the expression of target genes. Furthermore, 170 ASlncRNAs were identified as potential miRNA precursors, suggesting that these ASlncRNAs may be involved in the regulation of muscle development by producing miRNA precursors. Our results provide a catalog of goat muscle-related ASlncRNAs, and will contribute to a fuller understanding of the roles of ASlncRNAs in muscle development.
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MicroARNs , ARN Largo no Codificante , Animales , Perfilación de la Expresión Génica/métodos , Cabras/genética , MicroARNs/genética , Desarrollo de Músculos/genética , ARN Largo no Codificante/genética , TranscriptomaRESUMEN
CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.
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Inflamación , Cicatrización de Heridas , Humanos , TemperaturaRESUMEN
The long non-coding RNAs (lncRNAs) are emerging as essential regulators of the growth and development of skeletal muscles. However, little is known about the expression profiles of lncRNAs during the proliferation and differentiation of skeletal muscle satellite cells (MuSCs) in goats. In this study, we investigate potential regulatory lncRNAs that govern muscle development by performing lncRNA expression profiling analysis during the proliferation (cultured in the growth medium, GM) and differentiation (cultured in the differentiation medium, DM1/DM5) of MuSCs. In total, 1001 lncRNAs were identified in MuSC samples, and 314 differentially expressed (DE) (FDR < 0.05, |log2FC| > 1) lncRNAs were screened by pairwise comparisons from three comparison groups (GM-vs-DM1, GM-vs-DM5, DM1-vs-DM5). Moreover, we identified the cis-, trans-, and antisense-regulatory target genes of DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these target genes were significantly enriched in muscle development-related GO terms and KEGG pathways. In addition, the network of interactions between DE lncRNAs and their target genes was identified, which included well-known myogenesis regulators such as Myogenic differentiation 1 (MyoD), Myogenin (MyoG), and Myosin heavy chain (MyHC). Meanwhile, competing endogenous RNA (ceRNA) network analysis showed that 237 DE lncRNAs could bind to 329 microRNAs (miRNAs), while miRNAs could target 564 mRNAs. Together, our results provide a genome-wide resource of lncRNAs that may contribute to myogenic differentiation in goats and lay the groundwork for future investigation into their functions during skeletal muscle development.
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MicroARNs , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cabras/genética , Cabras/metabolismo , Redes Reguladoras de Genes , Perfilación de la Expresión Génica/métodos , MicroARNs/genética , MicroARNs/metabolismo , Diferenciación Celular/genética , Desarrollo de Músculos/genética , TranscriptomaRESUMEN
Cadmium (Cd) is one of the most toxic environmental pollutants affecting the growth and reproduction of various plants. Analysis of the biological adaptation and tolerance mechanisms of the hyperaccumulator Erigeron annuus to Cd stress may help identify new plant species for phytoremediation and in optimizing the process. This study is to the first to analyze the molecular composition and diversity of dissolved organic matter (DOM) secreted by roots using FT-ICR MS, and multiple physiological and biochemical indexes of E. annuus seedlings grown in solutions containing 0-200 Cd µmol L-1. The results showed that E. annuus had strong photosynthetic adaptation and protection ability under Cd stress. Cd was immobilized or compartmentalized by cell walls and vacuoles in the plant, thus alleviating Cd stress. Activation of anti-oxidation defense mechanisms also played an important role in alleviating or eliminating Cd toxicity in E. annuus. High Cd stress promoted production of a higher proportion of new molecules in DOM secreted by E. annuus roots compared to low Cd stress. DOM secreted by roots contributed to plant resistance to Cd-induced stress via producing more carbohydrates, aromatic structures and tannins. Results indicate the mechanisms underpinning the potential use of E. annuus as a phytoremediator in environments with moderate Cd pollution.
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Biodegradación Ambiental , Cadmio/toxicidad , Erigeron/fisiología , Contaminantes del Suelo/toxicidad , Tolerancia a Medicamentos , Exudados y Transudados , Oxidación-Reducción , Raíces de Plantas/crecimiento & desarrollo , Plantas , PlantonesRESUMEN
Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.
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Catequina/análogos & derivados , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Antioxidantes/farmacología , Vendajes/tendencias , Catequina/metabolismo , Catequina/farmacología , Cicatriz/prevención & control , Humanos , Hidrogeles/farmacología , Piel/efectos de los fármacos , Piel/metabolismo , Té/metabolismo , Cicatrización de Heridas/fisiologíaRESUMEN
The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM-1 s-1), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T1-MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.
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Ferrocianuros/química , Ácido Hialurónico/administración & dosificación , Indoles/química , Fármacos Fotosensibilizantes/administración & dosificación , Polímeros/química , Porfirinas/administración & dosificación , Neoplasias del Cuello Uterino/terapia , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Clorofilidas , Endocitosis/efectos de los fármacos , Femenino , Células HeLa , Humanos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Imagen por Resonancia Magnética , Ratones , Células 3T3 NIH , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Porfirinas/química , Nanomedicina Teranóstica , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Many cell death regulators physically or functionally interact with metabolic enzymes. These interactions provide insights into mechanisms of anticancer treatments from the perspective of tumor cell metabolism and apoptosis. Recent studies have shown that zinc and p53 not only induce tumor cell apoptosis, but also regulate tumor cell metabolism. However, the underlying mechanism is complex and remains unclear, making further research imperative to provide clues for future cancer treatments. In this study, we found that hexokinase 2 (HK2), which has dual metabolic and apoptotic functions, is downstream of zinc and p53 in both prostate cancer patient tissue and prostate cancer cell lines. Notably, the mitochondrial location of HK2 is crucial for its function. We demonstrate that zinc and p53 disrupt mitochondrial binding of HK2 in prostate cancer cells by phosphorylating VDAC1, which is mediated by protein kinase B (Akt) inhibition and glycogen synthase kinase 3ß (GSK3ß) activation. In addition, we found that zinc combined with p53 significantly inhibited tumor growth in a prostate cancer cell xenograft model. Therefore, interference of the mitochondrial localization of HK2 by zinc and p53 may provide a new treatment approach for cancer.
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Hexoquinasa/metabolismo , Mitocondrias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Zinc/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A composite of Ag3PO4@g-C3N4 with the Z-scheme structure was synthesized, and used as the photoanode in a photocatalytic fuel cell (PFC). With the help of the Z-scheme design, both the degradation of tetracycline and the output of maximum power density (Pmax) were greatly enhanced in this PFC system. The degradation rate of tetracycline in the Ag3PO4@g-C3N4 PFC was 2.53 times and 3.65 times that in the PFC systems with the Ag3PO4 photoanode and the g-C3N4 photoanode, respectively. The Pmax of the Ag3PO4@g-C3N4 PFC was 6.06⯵Wâ¯cm-2, which was 1.46 times and 90.4 times that of the Ag3PO4 PFC (4.16⯵Wâ¯cm-2) and the g-C3N4 PFC (0.067⯵Wâ¯cm-2), respectively. The possible mechanism was proposed. The Z-scheme photoanode could not only contribute to the separation of photogenerated carriers to achieve a high photocatalytic activity, but also reserve a good redox capacity. Additionally, aeration played an important role on the PFC performance. It was demonstrated that N2 purging facilitated the electricity generation, while O2 purging promoted the pollutant degradation.
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Luz , Plata , Antibacterianos , Catálisis , TetraciclinaRESUMEN
Adipose-derived stem cells (ADSCs) have emerged as a cell source for regeneration medicine. ADSCs possess the capacity to differentiate into endothelial cells and serve an essential role in vascular development and function. LncRNA taurine upregulated gene 1 (TUG1) has recently been linked with angiogenesis in hepatoblastoma. However, the roles of TUG1 in endothelial differentiation of ADSCs remain unidentified. Human adipose-derived stem cells (hADSCs) were obtained and characterized by flow cytometry, Oil red O and Alizarin Red staining. HADSCs were maintained in the endothelial differentiation medium and the expressions of TUG1, miR-143, and FGF1 were examined by qRT-PCR. To assess endothelial differentiation, the expressions of CD31, von Willebrand factor (vWF), VE-cadherin were examined by Western blot analysis, qRT-PCR, and immunofluorescence. Tube formation in Matrigel was examined. The interactions between TUG1 and miR-143, miR-143 and FGF1 were validated by luciferase assays. During the endothelial differentiation process, TUG1 and FGF1 were upregulated, whereas miR-143 was downregulated. TUG1 overexpression downregulated miR-143, upregulated FGF1, CD31, vWF, and VE-cadherin, and enhanced capillary tube formation. Luciferase assays showed that TUG1 interacted with miR-143, and FGF1 was a direct target of miR-143. Furthermore, the enhancement of endothelial differentiation induced by TUG1 overexpression was abolished by miR-143 overexpression. Our findings implicated that lncRNA TUG1 promoted endothelial differentiation of ADSCs by regulating the miR-143/FGF1 axis.
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Tejido Adiposo/metabolismo , Diferenciación Celular , Células Endoteliales/metabolismo , Factor 1 de Crecimiento de Fibroblastos/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Células Madre/metabolismo , Tejido Adiposo/citología , Células Endoteliales/citología , Factor 1 de Crecimiento de Fibroblastos/genética , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Células Madre/citologíaRESUMEN
BACKGROUND: Paclitaxel (PTX) is a first-line chemotherapeutic drug for the treatment of prostate cancer. However, most patients develop resistance and metastasis, and thus new therapeutic approaches are urgently required. Recent studies have identified widespread anti-tumor effects of zinc (Zn) in various tumor cell lines, especially prostate cancer cells. In this study, we examined the effects of Zn as an adjuvant to PTX in prostate cancer cells. METHODS: PC3 and DU145 cells were treated with different concentrations of Zn and/or PTX. MTT assay was used to detect cell viability. Real-time cell analysis (RTCA) and microscopy were used to observe morphological changes in cells. Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. qPCR (reverse transcription-polymerase chain reaction) was used to examine changes in TWIST1 mRNA levels. Cell invasion and migration were detected by scratch and transwell assays. shRNA against TWIST1 was used to knockdown TWIST1. Colony formation assay was used to detect cell proliferation, while Annexin V and propidium iodide (PI) staining was used to detect cell apoptosis. RESULTS: Zn and PTX increased proliferation inhibition in a dose- and time-dependent manner in prostate cancer cells, while Zn increased prostate cancer cell chemosensitivity to PTX. Combined Zn and PTX inhibited prostate cancer cell invasion and migration by downregulating the expression of TWIST1. Furthermore, knockdown of TWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, Zn and PTX reduced cell proliferation and induced apoptosis in prostate cancer cells. CONCLUSIONS: Our results demonstrated that Zn and PTX combined therapy inhibits EMT by reducing the expression of TWIST1, which reduces the invasion and migration of prostate cancer cells. SiTWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, with prolonged treatment, Zn and PTX inhibited proliferation and led to prostate cancer cell apoptosis. Therefore, Zn may be a potential adjuvant of PTX in treating prostate cancer and combined treatment may offer a promising therapeutic strategy for prostate cancer.
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Apoptosis/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Paclitaxel/farmacología , Próstata , Neoplasias de la Próstata , Zinc , Adyuvantes Farmacéuticos/metabolismo , Adyuvantes Farmacéuticos/farmacología , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Proteínas Nucleares/metabolismo , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteína 1 Relacionada con Twist/metabolismo , Zinc/metabolismo , Zinc/farmacologíaRESUMEN
Given the multiple interactions between neutrophils (NEs) and atherosclerosis (AS), in this study, we exploited NEs as cellular vehicles loaded with cationic liposomes for actively targeting atherosclerotic sites. The cellular vehicles based on NEs possess efficient internalization of cationic liposomes and sensitive response to the chemotaxis of atherosclerotic inflammatory cells, which ultimately realize the targeted delivery of the cargos into the target cells in vitro. Moreover, these effects also translated to significant enhancement of the accumulation of NEs' cargos into the atherosclerotic plaque in vivo after administering NE vehicles to the AS animal model. Consequently, cellular vehicles based on NEs could be a novel strategy for targeted delivery of payloads into atherosclerotic plaque, which would facilitate theranostics for AS and the development of anti-AS drugs to manage the disease.
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Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Neutrófilos/metabolismo , Placa Aterosclerótica/tratamiento farmacológico , Animales , Aorta/metabolismo , Apolipoproteínas E/genética , Línea Celular , Modelos Animales de Enfermedad , Liberación de Fármacos , Estabilidad de Medicamentos , Liposomas/farmacocinética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Nanomedicina/métodos , Tamaño de la Partícula , Distribución TisularRESUMEN
Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function. Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status. AMPK compensated for energy loss by increasing glycolysis. The impact of this was assessed by reducing glucose levels in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis and AMPK. The combination of these factors with metformin intensified cytotoxicity through further downregulation of ATP. Our study outlines an important role for SIRT3 in the antitumor effect of mitochondrial complex I inhibitors in human ovarian cancer cells. This effect appears to be mediated by induction of energy stress and apoptosis. Strategies that target the mitochondria could be enhanced by modulating glycolysis to further aggravate energy stress that may increase the antitumor effect.
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Antineoplásicos/farmacología , Apoptosis , Metformina/farmacología , Mitocondrias/efectos de los fármacos , Neoplasias Ováricas/metabolismo , Sirtuina 3/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Línea Celular Tumoral , Complejo I de Transporte de Electrón/metabolismo , Femenino , Glucosa/metabolismo , Humanos , Mitocondrias/metabolismo , Neoplasias Ováricas/patología , Sirtuina 3/biosíntesis , Estrés FisiológicoRESUMEN
Alumina ceramic is a highly promising material for fabricating high-temperature pressure sensors. In this paper, a direct bonding method for fabricating a sensitive cavity with alumina ceramic is presented. Alumina ceramic substrates were bonded together to form a sensitive cavity for high-temperature pressure environments. The device can sense pressure parameters at high temperatures. To verify the sensitivity performance of the fabrication method in high-temperature environments, an inductor and capacitor were integrated on the ceramic substrate with the fabricated sensitive cavity to form a wireless passive LC pressure sensor with thick-film integrated technology. Finally, the fabricated sensor was tested using a system test platform. The experimental results show that the sensor can realize pressure measurements above 900 °C, confirming that the fabricated sensitive cavity has excellent sealing properties. Therefore, the direct bonding method can potentially be used for developing all-ceramic high-temperature pressure sensors for application in harsh environments.
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Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the NF-κB signaling pathway and K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using siRNA. Furthermore, deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the NF-κB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor proliferative capacity and high levels of apoptosis in SKOV3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of NF-κB signaling that is partly dependent on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.
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Resistencia a Antineoplásicos/fisiología , FN-kappa B/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Proteínas de Complejo Poro Nuclear/metabolismo , Neoplasias Ováricas/patología , Proteínas de Unión al ARN/metabolismo , Proteína Sequestosoma-1/metabolismo , Antineoplásicos/farmacología , Western Blotting , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Cisplatino/farmacología , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoprecipitación , Microscopía Confocal , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de SeñalRESUMEN
There are two main types of fluid in bone tissue: blood and interstitial fluid. The metabolism of cells mainly relies on the microenvironment of the interstitial fluid. Researches of osteonal fluid seepage behavior based on the microstructure of bone tissue have become a hot point. The aim of the present research work is to assess the effect of blood pressure oscillation on the osteonal interstitial fluid seepage behavior. We established finite element osteon models for a hollow and that considering blood pressure oscillation, respectively, with COMSOL Multiphysics software in order to compare their fluid flow behavior under the axial loading. The results predicted that the interstitial fluid pressure field was enlarged considering the blood pressure oscillation, while the velocity filed changed little. Specifically, the increase of blood pressure oscillatory amplitude could result in the increase of osteonal interstitial fluid pressure, while the blood pressure oscillatory frequency had limited effects on the osteonal pore fluid pressure. Moreover, the blood pressure oscillatory amplitude and frequency had no effect on the osteonal interstitial fluid velocity. The finite element model can be used for the study of the poroelastic behaviors of the osteon under non-axisymmetric loads and microcracks, and can also be a new way to study the mechanism of bone mechanotransduction and electromechanotransduction.