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Globally, microplastic pollution of soil ecosystems poses a major risk. The early studies found that the impact of microplastics on different plants could vary depending on the type of microplastic, the mass concentration or the plant species. This study investigated the effect of 3 mass concentrations (0.1%, 1%, and 2.5%) and 3 types of microplastics (PE MPs, PLA MPs, and PVC MPs) on adzuki bean biomass, root traits, Chlorophyll content and antioxidant enzymes. According to our findings, all microplastics had an impact on biomass, but PLA MPs had the strongest inhibitory effect. The high mass concentration of microplastics had a significant influence on chlorophyll content. Adzuki beans exhibited varying degrees of damage upon exposure to microplastics, but they were able to withstand the oxidative stress brought on by PE MPs by increasing the activity of antioxidant enzymes (SOD and POD). Comparing the adverse effects of PE MPs on adzuki beans to those of PLA MPs and PVC MPs, principal component analysis and membership function value analysis revealed that the former had fewer impacts. Disparities in the observed effects may be attributed to variations in the properties of microplastics. Subsequent investigations into the mechanisms underlying microplastic toxicity need a more comprehensive exploration.
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Clorofila , Microplásticos , Contaminantes del Suelo , Vigna , Vigna/efectos de los fármacos , Microplásticos/toxicidad , Clorofila/metabolismo , Contaminantes del Suelo/toxicidad , Biomasa , Raíces de Plantas/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , AntioxidantesRESUMEN
Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from salivary EVs to distinguish oral squamous cell carcinoma (OSCC) patients from healthy individuals and explore the feasibility to evaluate therapeutical outcomes. Bi-functionalized magnetic beads (BiMBs) with Ti (IV) ions and a lipid analog, 1,2-Distearoyl-3-sn-glycerophosphoethanolamine (DSPE) are developed to efficiently isolate EVs from small volume of saliva. In the discovery stage, label-free proteomics and phosphoproteomics quantification showed 315 upregulated proteins and 132 upregulated phosphoproteins in OSCC patients among more than 2500 EV proteins and 1000 EV phosphoproteins, respectively. We further applied targeted proteomics by coupling parallel reaction monitoring with parallel accumulation-serial fragmentation (prm-PASEF) to measure panels of proteins and phosphoproteins from salivary EVs collected before and after surgical resection. A panel of three total proteins and three phosphoproteins, most of which have previously been associated with OSCC and other cancer types, show sensitive response to the therapy in individual patients. Our study presents a novel strategy to the discovery of effective biomarkers for non-invasive assessment of OSCC surgical outcomes with small amount of saliva.
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Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Biomarcadores de Tumor/metabolismo , Proteómica , Vesículas Extracelulares/metabolismo , Fosfoproteínas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Saliva/metabolismoRESUMEN
Plastic pollution and antibiotic resistance are two emerging environmental and human health crises today. Although it was revealed that microplastics can serve as vectors for the dissemination of antibiotic resistance, it is still unclear how the nanoplastics influence the horizontal transfer of antibiotic resistance genes (ARGs). Herein, we firstly compared the effect of polystyrene (PS) micro/nanoplastics on the transformation of plasmid-borne ARG, using a transformation model consisting of plasmid pUC19 (ampR ) and Escherichia coli DH5α (recipient). Due to its size effect, PS nanoplastics (10-500 mg/L) significantly enhanced the transformation efficiency (2.8-5.4 folds) and frequency (3.2-8.4 folds) of exogenous ampR into E. coli, while PS microplastics exerted no influence. The detailed mechanisms were found that nanoplastics induced reactive oxygen species (ROS) overproduction, activated SOS response, increased cell membrane permeability and changed the secretion systems, thereby facilitating the uptake of exogenous DNA by bacteria. Moreover, the co-presences of nanoplastics with humic acid or Fe3+ relieved to some extent, but did not completely alleviate the promoting effect of nanoplastics on plasmid transformation. Our findings suggest that the risk of nanoplastics on promoting the dissemination of antibiotic resistance should not be neglected, and further studies are needed to investigate such risk in complex environments.
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Escherichia coli , Microplásticos , Adenosina Monofosfato , Ampicilina/farmacología , Resistencia a la Ampicilina , Antibacterianos/farmacología , Escherichia coli/genética , Humanos , Sustancias Húmicas , Plásmidos/genética , Plásticos , Poliestirenos/farmacología , Especies Reactivas de OxígenoRESUMEN
In this paper, we propose an image-based key frame gating method to reduce motion artifacts in intravascular ultrasound (IVUS) longitudinal cuts. The artifacts are mainly caused by the periodic relative displacement between blood vessels and the IVUS catheter due to cardiac motion. The method is achieved in four steps as following. Firstly, we convert IVUS image sequences to polar coordinates to cut down the amount of calculation. Secondly, we extracted a one-dimensional signal cluster reflecting cardiac motion by spectral analysis and filtering techniques. Thirdly, we designed a Butterworth band-pass filter for filtering the one-dimensional signal clusters. Fourthly, we retrieved the extremes of the filtered signal clusters to seek key frames to compose key-frames gated sequences. Experimental results showed that our algorithm was fast and the average frame processing time was 17ms. Observing the longitudinal viewpictures, we found that comparing to the original ones, the gated sequences had similar trend, less saw tooth shape, and good continuity. We selected 12 groups of clinical IVUS sequences [images (876 +/- 65 frames), coronary segments length (14.61 +/- 1.08 mm)] to calculate vessel volume, lumen volume, mean plaque burden of the original and gated sequences. Statistical results showed that, on one hand, both vessel volume and lumen volume measured of the gated sequences were significantly smaller than those of the original ones, and there was no significant difference on mean plaque burden between original and gated sequences, which met the need of the clinical diagnosis and treatment. On the other hand, variances of vessel area and lumen area of the gated sequences were significantly smaller than those of the original sequences, indicating that the gated sequences would be more stable than the original ones.
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Corazón , Ultrasonografía Intervencional , Algoritmos , Artefactos , Humanos , Movimiento (Física)RESUMEN
PURPOSE: The aim of this study was to evaluate the long-term effects of serial intravitreal injections (IVI) on measures of dry eye. METHODS: The PubMed, EMBASE, and Cochrane databases were searched according to the PROSPERO protocol (CRD42023455727). Studies evaluating the influence of serial IVI on the ocular surface compared with untreated fellow eyes were included. The measures of dry eye after IVI were used as outcome variables. The results are presented as mean difference (MD) with a corresponding 95% confidence interval (CI). RESULTS: A total of 4 studies with 259 participants were included in this meta-analysis. Significant increases in ocular surface disease index (OSDI) scores (MD 10.26, 95 % CI 5.05 to 15.46, p ï¼ 0.01) and tear film osmolarity (TOsm; MD 4.40, 95 % CI 0.87 to 7.92, p = 0.01) were observed in the IVI treated eyes compared to the untreated fellow eyes. There was no significant difference between the groups with respect to fluorescein tear film break-up time (TBUT; p = 0.05), average non-invasive tear film break-up time (NITBUT; p = 0.94), first NITBUT (p = 0.78) and Schirmer test (p = 0.94). CONCLUSION: Repeated IVI of anti-VEGF agents with preoperative povidone-iodine application was associated with increased OSDI scores and TOsm, while no significant difference was found in fluorescein TBUT, average NITBUT, first NITBUT and Schirmer test. The ocular surface may partially recover after the procedures, but IVI still has deleterious effects on the ocular surface.
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Síndromes de Ojo Seco , Humanos , Inyecciones Intravítreas , Síndromes de Ojo Seco/tratamiento farmacológico , Povidona Yodada , Lágrimas , FluoresceínaRESUMEN
Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.
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The threat of microplastic pollution in soil ecosystems has caused widespread concern. In order to clarify the effect of polyethylene microplastics on soil properties, a 4-month soil incubation experiment was conducted in this study to investigate the effect of different mass fraction (1 %, 2.5 %, and 5 %) and particle sizes (30 mesh and 100 mesh) of polyethylene microplastics on soil chemical properties, nutrient contents, and enzyme activities. The results showed that:â When the particle size was 100 mesh, microplastics at the mass concentrations of the 2.5 % and 5 % treatments significantly reduced soil pH, and the exposure of polyethylene microplastics had no significant effect on soil conductivity. â¡ Compared to that in CK, the addition of microplastics reduced soil available potassium, available phosphorus, and nitrate nitrogen to varying degrees. The addition of 100 mesh microplastics significantly increased soil organic matter and ammonium nitrogen. ⢠When the particle size was 100 mesh, compared to that in CK, treatments of all concentrations significantly increased soil catalase activity and alkaline phosphatase, showing an increasing but not significant trend, and the 5 % concentration treatment significantly decreased soil sucrase activity. ⣠Changes in soil properties were influenced by the addition of microplastics of different concentrations and sizes, with higher concentrations and smaller particle sizes having more significant effects. In conclusion, the effects of microplastics on soil properties were not as pronounced as expected, and future research should focus on the mechanisms involved in the different effects.
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Microplásticos , Fósforo , Polietileno , Contaminantes del Suelo , Suelo , Suelo/química , Contaminantes del Suelo/análisis , Fósforo/análisis , Nitrógeno , Catalasa/metabolismo , Nutrientes/análisis , Tamaño de la Partícula , Fosfatasa Alcalina/metabolismoRESUMEN
Biodegradable mulch residues contribute significantly to the presence of microplastics in soil ecosystems. The environmental impact of microplastics, especially biodegradable microplastics (bio-MPs), on soil and plants is of increasing concern. In this study, the responses of five crop species potted in soil treated with different mass concentrations of bio-MPs were assessed for one month. The shoot and root biomasses of cabbages and strawberries were inhibited by bio-MPs treatment. There was little variation in the growth indicators of identical plants with the addition of different mass concentrations of bio-MPs; however, a significant difference was observed among different plants with the addition of the same concentration of bio-MPs. The detrimental effects of bio-MPs were more pronounced in strawberries and cabbages than in the other plant species. Moreover, bio-MPs can affect the availability of soil nutrients and enzyme activities. Structural equation modeling showed that changes in soil properties may indirectly affect plant growth and nutrient uptake when exposed to bio-MPs. This study provides a theoretical basis for understanding the ecological effects of biodegradable mulch films.
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Biodegradación Ambiental , Microplásticos , Contaminantes del Suelo , Suelo , Suelo/química , Microplásticos/toxicidad , Desarrollo de la Planta/efectos de los fármacos , Plásticos Biodegradables , Plantas/efectos de los fármacosRESUMEN
The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the "one stone, three birds" strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.
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Antibacterianos , Ginsenósidos , Ácido Hialurónico , Agujas , Polímeros , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Ginsenósidos/farmacología , Ginsenósidos/química , Ginsenósidos/administración & dosificación , Polímeros/química , Polímeros/farmacología , Ratones , Indoles/química , Indoles/farmacología , Berberina/farmacología , Berberina/química , Berberina/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/administración & dosificación , Biopelículas/efectos de los fármacos , Solubilidad , Nanopartículas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Pruebas de Sensibilidad MicrobianaRESUMEN
In the agricultural lands of China, polyethylene is the main component of microplastics ï¼MPsï¼, with characteristics such as small size, wide distribution, easy accumulation, and difficult degradation. Therefore, it may have an impact on the elemental cycling process of the soil. On the basis of reviewing the key literatures in the past few years, this study systematically analyzed and summarized the key factors and processes of the polyethylene microplastics ï¼PE-MPsï¼ affecting soil nitrogen transformation. On the one hand, PE-MPs directly affected the activities of microorganisms and key enzymes related to soil nitrogen transformation by enriching microorganisms, selecting colonized microbial populations, and releasing additives. On the other hand, PE-MPs had indirect impacts on the activities of microorganisms and key enzymes related to soil nitrogen transformation by affecting soil physicochemical properties of soil and changing the microenvironment for microbial growth. Moreover, phthalates, an important additive of the MPs, may be the key factor affecting soil nitrogen transformation in the short-term. Finally, we posed key scientific issues that should be further studied in order to provide scientific support for nitrogen nutrition regulation and ecological risk assessment of soils contaminated by PE-MPs.
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Microplásticos , Nitrógeno , Polietileno , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Suelo/química , Microbiología del Suelo , ChinaRESUMEN
As a widespread pollutant in the environment, research on microplastics have attracted much attention. This review systematically analyzed the interaction between microplastics and soil microorganisms based on existing literatures. Microplastics can change the structure and diversity of soil microbial communities directly or indirectly. The magnitude of these effects depends on the type, dose and shape of microplastics. Meanwhile, soil microorganisms can adapt to the changes caused by microplastics through forming surface biofilm and selecting population. This review also summarized the biodegradation mechanism of microplastics, and explored the factors affecting this process. Microorganisms will firstly colonize the surface of microplastics, and then secrete a variety of extracellular enzymes to function at specific sites, converting polymers into lower polymers or monomers. Finally, the depolymerized small molecules enter the cell for further catabolism. The factors affecting this degradation process are not only the physical and chemical properties of the microplastics, such as molecular weight, density and crystallinity, but also some biological and abiotic factors that affect the growth and metabolism of related microorganisms and the enzymatic activities. Future studies should focus on the connection with the actual environment, and develop new technologies of microplastics biodegradation to solve the problem of microplastic pollution.
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Microplásticos , Plásticos , Suelo , Polímeros , Biodegradación AmbientalRESUMEN
Dental pulp stem cells (DPSCs) have received a lot of attention as a regenerative medicine tool with strong immunomodulatory capabilities. The excessive inflammatory response involves a variety of immune cells, cytokines, and has a considerable impact on tissue regeneration. The use of DPSCs for controlling inflammation for the purpose of treating inflammation-related diseases and autoimmune disorders such as supraspinal nerve inflammation, inflammation of the pulmonary airways, systemic lupus erythematosus, and diabetes mellitus is likely to be safer and more regenerative than traditional medicines. The mechanism of the anti-inflammatory and immunomodulatory effects of DPSCs is relatively complex, and it may be that they themselves or some of the substances they secrete regulate a variety of immune cells through inflammatory immune-related signaling pathways. Most of the current studies are still at the laboratory cellular level and animal model level, and it is believed that through the efforts of more researchers, DPSCs/SHED are expected to be transformed into excellent drugs for the clinical treatment of related diseases.
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Pulpa Dental , Células Madre , Animales , Diferenciación Celular , Inflamación , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
The poor bacterial loading capacity and biocompatibility of the anode lead to weak electricity production performance of microbial fuel cells (MFCs). Inspired by kelp, we developed a double-layer hydrogel bioanode based on sodium alginate (SA). The inner hydrogel layer of encapsulated Fe3O4 and electroactive microorganisms (EAMs) was used as the bioelectrochemical catalytic layer. The outer hydrogel layer formed by cross-linking SA with polyvinyl alcohol (PVA) was used as the protective layer. The 3D porous structure of the inner hydrogel formed based on Fe3O4 facilitated the electroactive bacteria colonization and electron transfer, while the high structural toughness, salt-resistance and antibacterial properties of the outer highly cross-linked hydrogel served to protect the catalytic layer for stable electricity production. When high-salt waste leachate was used as the nutrient, the amazing open-circuit voltage (OCV) of 1.17 V and the operating voltage of 781 mV were brought by the double-layer hydrogel bioanode PVA@SA&Fe3O4/EAMs@SA.
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Fuentes de Energía Bioeléctrica , Salinidad , Alginatos/química , Hidrogeles , Electricidad , Alcohol Polivinílico/química , Cloruro de SodioRESUMEN
Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
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Microplastics(MPs), as a new type of environmental pollutants, have gradually attracted widespread attention since they were introduced by British scientists in 2004. Soil is an important accumulation site for microplastics, which can expand the scope of contamination and accumulate with agricultural practices such as irrigation and tillage. Microplastics in soil cause a variety of toxicities to terrestrial plants. The small particle size, difficult degradation, and strong adsorption capacity bring a challenge to the microplastic pollution treatment of soil. In this study, the toxicity of microplastics to terrestrial plants was reviewed in terms of their direct or indirect toxicity and combined effects with other pollutants, mainly in terms of mechanical injury, induction of oxidative stress, and cytotoxicity and genotoxicity to plants, resulting in plant growth and plant tissue metabolism obstruction. In general, the toxicity of microplastics depended on the polymer type, size, and dose; plant tolerance; and exposure conditions. In addition, the production of secondary microplastics and endogenous contaminants during their degradation in soil enhanced the biotoxicity of microplastics. Further, the physical, chemical, and microbial degradation mechanisms of microplastics were introduced in this study based on the current research. At first, the physical and chemical degradation of microplastics mainly occurred by changing the particle size and surface properties of microplastics and producing intermediates. Then, smaller-sized microplastics and their intermediates could eventually be converted to water and carbon dioxide through physical, chemical, and biological functions. Finally, further prospects regarding soil microplastics were introduced, and we provided information for future improvement and pollution control of microplastics.
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Contaminantes Ambientales , Contaminantes del Suelo , Microplásticos/toxicidad , Suelo/química , Plásticos/toxicidad , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Agricultura , Plantas , EcosistemaRESUMEN
Aerobic vaginitis (AV) is a gynecological disease associated with vaginal flora imbalance. The nonselective bactericidal nature of antibiotics and low customization rate of probiotic supplementation in existing treatments lead to AV recurrence. Here, a drug delivery strategy is proposed that works with the changing dynamics of the bacterial flora. In particular, a core-shell nanogel (CSNG) is designed to encapsulate prebiotic inulin and antimicrobial peptide Cath 30. The proposed strategy allows for the sequential release of both drugs using gelatinase produced by AV pathogenic bacteria, initially selectively killing pathogenic bacteria and subsequently promoting the proliferation of beneficial bacteria in the vagina. In a simulated infection environment in vitro, the outer layer of CSNGs, Cath 30 is rapidly degraded and potently killed the pathogenic bacterium Staphylococcus aureus at 2-6 h. CSNGs enhances proliferation of the beneficial bacterium Lactobacillus crispatus by more than 50% at 24 h. In a rat AV model, the drug delivery strategy precisely regulated the bacterial microenvironment while controlling the inflammatory response of the vaginal microenvironment. This new treatment approach, configured on demand and precisely controlled, offers a new strategy for the treatment of vaginal diseases.
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Vaginitis , Vaginosis Bacteriana , Femenino , Humanos , Animales , Ratas , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Nanogeles , Vaginitis/tratamiento farmacológico , Vaginitis/microbiología , Vagina , Bacterias , Bacterias Aerobias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , EsterilizaciónRESUMEN
A cancer-mitochondria dual-targeting nanoparticle based on lactose and ferrocenium derivatives conjugated polydopamine (PDA@Lac/Fc/Hyp) was constructed, which exhibited cancer-targeting and mitochondria-targeting ability deriving from lactose and ferrocenium derivatives due to the specific carbohydrate-protein interaction and cationic species properties, respectively. Moreover, PDA@Lac/Fc/Hyp showed great biocompatibility and phototherapeutic efficiency. This work displays a good example of constructing cancer-mitochondria dual-targeting nanoparticle for synergistic phototherapy.
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Antineoplásicos/farmacología , Compuestos Ferrosos/farmacología , Glicoles/farmacología , Indoles/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Fotoquimioterapia , Polímeros/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Ferrosos/química , Glicoles/química , Células Hep G2 , Humanos , Indoles/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Mitocondrias/metabolismo , Estructura Molecular , Nanopartículas/química , Polímeros/química , Relación Estructura-ActividadRESUMEN
Traumatic brain injury (TBI) contributes to the key causative elements of neurological deficits. However, no effective therapeutics have been developed yet. In our previous work, extracellular vesicles (EVs) secreted by stem cells from human exfoliated deciduous teeth (SHED) offered new insights as potential strategies for functional recovery of TBI. The current study aims to elucidate the mechanism of action, providing novel therapeutic targets for future clinical interventions. With the miRNA array performed and Real-time PCR validated, we revealed the crucial function of miR-330-5p transferred by SHED-derived EVs (SHED-EVs) in regulating microglia, the critical immune modulator in central nervous system. MiR-330-5p targeted Ehmt2 and mediated the transcription of CXCL14 to promote M2 microglia polarization and inhibit M1 polarization. Identified in our in vivo data, SHED-EVs and their effector miR-330-5p alleviated the secretion of inflammatory cytokines and resumed the motor functional recovery of TBI rats. In summary, by transferring miR-330-5p, SHED-EVs favored anti-inflammatory microglia polarization through Ehmt2 mediated CXCL14 transcription in treating traumatic brain injury.
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Lesiones Traumáticas del Encéfalo , Quimiocinas CXC , Vesículas Extracelulares , N-Metiltransferasa de Histona-Lisina , MicroARNs , Microglía , Animales , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/terapia , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Microglía/metabolismo , Ratas , Células Madre/metabolismoRESUMEN
Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo. Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.
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Antibacterianos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Péptidos/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Piranos/farmacología , Vitamina E/química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Piranos/administración & dosificación , Piranos/química , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing. PURPOSE: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus. METHODS: PGO-OH30 nanoparticles were prepared by π-π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated. RESULTS: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P<0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P<0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group. CONCLUSION: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.