RESUMEN
Implantable neural microelectrodes exhibit the great ability to accurately capture the electrophysiological signals from individual neurons with exceptional submillisecond precision, holding tremendous potential for advancing brain science research, as well as offering promising avenues for neurological disease therapy. Although significant advancements have been made in the channel and density of implantable neural microelectrodes, challenges persist in extending the stable recording duration of these microelectrodes. The enduring stability of implanted electrode signals is primarily influenced by the chronic immune response triggered by the slight movement of the electrode within the neural tissue. The intensity of this immune response increases with a higher bending stiffness of the electrode. This Review thoroughly analyzes the sequential reactions evoked by implanted electrodes in the brain and highlights strategies aimed at mitigating chronic immune responses. Minimizing immune response mainly includes designing the microelectrode structure, selecting flexible materials, surface modification, and controlling drug release. The purpose of this paper is to provide valuable references and ideas for reducing the immune response of implantable neural microelectrodes and stimulate their further exploration in the field of brain science.
Asunto(s)
Electrodos Implantados , Microelectrodos , Humanos , Animales , Neuronas/inmunología , Neuronas/fisiología , Encéfalo/inmunología , Encéfalo/fisiologíaRESUMEN
Rice is a dominant source of inorganic arsenic (As) exposure for populations consuming rice as a staple food. Decreasing As accumulation in rice grain is important for improving food safety. Arsenite [As(III)], the main form of As in paddy soil porewater, is taken up inadvertently by OsLsi1 and OsLsi2, the two key transporters for silicon (Si) uptake in rice roots. Here, we investigated whether editing OsLsi1 or OsLsi2 can decrease As accumulation in rice grain without compromising grain yield. We used the CRISPR-Cas9 technology to edit the promoter region of OsLsi1 and the C-terminal coding sequence of OsLsi1 and OsLsi2, and we generated a total of 27 mutants. Uptake and accumulation of Si and As were evaluated in both short-term hydroponic experiments and in a paddy field. Deletion of 1.2-2 kb of the OsLsi1 promoter suppressed OsLsi1 expression in roots and Si uptake markedly and did not affect As(III) uptake or grain As concentration. Some of the OsLsi1 and OsLsi2 coding sequence mutants showed large decreases in the uptake of Si and As(III) as well as large decreases in Si accumulation in rice husks. However, only OsLsi2 mutants showed significant decreases (by up to 63%) in the grain total As concentration. Editing OsLsi2 mainly affected the accumulation of inorganic As in rice grain with little effect on the accumulation of dimethylarsenate (DMA). Grain yields of the OsLsi2 mutants were comparable to those of the wild type. Editing OsLsi2 provides a promising way to reduce As accumulation in rice grain without compromising the grain yield.
Asunto(s)
Arsénico , Oryza , Contaminantes del Suelo , Silicio/metabolismo , Oryza/genética , Proteínas de Transporte de Membrana , Transporte Biológico , SueloRESUMEN
Porphyrin-based metal-organic frameworks (PMOFs) are a kind of crystal hybrid material with broad application prospects in energy, catalysis, biomedicine, and other fields. In this study, the La-TCPP PMOF nanocrystal was constructed using a porphyrin ligand and La ion. This material can produce a high loading rate on doxorubicin (DOX) owing to its special porous structure. The high loading rate of drug molecules and the reactive oxygen species (ROS) of the porphyrin ligand enable La-TCPP@DOX nanocrystal to produce a powerful killing effect on cancer cells under the synergistic attack of chemotherapy (CT) and photodynamic therapy (PDT). Finally, by modifying the targeted aptamer, the actual therapeutic effect of this special La-TCPP@DOX@Apt material on tumors was confirmed by applying the established mouse tumor model. The composite nanomaterial not only avoids the side effects caused by high concentrations of chemotherapeutic drugs, but also overcomes the limitation of PDT owing to insufficient light penetration and can inhibit and kill solid tumors under the condition of synergistic attack. This study is a complement to PMOF crystal materials, and its tumor-killing ability was achieved by loading drugs and introducing targeting molecules, which proves that the synergistic attack can more effectively inhibit and treat solid tumors. These studies have a reference and guiding significance for the treatment of cancer patients.
Asunto(s)
Estructuras Metalorgánicas , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Animales , Ratones , Estructuras Metalorgánicas/química , Ligandos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Doxorrubicina/química , Porfirinas/uso terapéuticoRESUMEN
Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based metal-organic frameworks (MOFs) that utilize porphyrin molecules as organic ligands have gained attention from researchers due to their excellent results as photosensitizers in tumor photodynamic therapy (PDT). Additionally, MOFs hold significant promise and potential for other tumor therapeutic approaches due to their tunable size and pore size, excellent porosity, and ultra-high specific surface area. Active delivery of nanomaterials via targeted molecules for tumor therapy has demonstrated greater accumulation, lower drug doses, higher therapeutic efficacy, and reduced side effects relative to passive targeting through the enhanced permeation and retention effect (EPR). This paper presents a comprehensive review of the targeting methods employed by porphyrin-based MOFs in tumor targeting therapy over the past few years. It further discusses the applications of porphyrin-based MOFs for targeted cancer therapy through various therapeutic methods. The objective of this paper is to provide a valuable reference and source of ideas for targeted therapy using porphyrin-based MOF materials and to inspire further exploration of their potential in the field of cancer therapy.
Asunto(s)
Estructuras Metalorgánicas , Neoplasias , Porfirinas , Humanos , Estructuras Metalorgánicas/farmacología , Porfirinas/farmacología , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Soil contamination with trace metals and metalloids can cause toxicity to plants and threaten food safety and human health. Plants have evolved sophisticated mechanisms to cope with excess trace metals and metalloids in soils, including chelation and vacuolar sequestration. Sulfur-containing compounds, such as glutathione and phytochelatins, play a crucial role in their detoxification, and sulfur uptake and assimilation are regulated in response to the stress of toxic trace metals and metalloids. This review focuses on the multi-level connections between sulfur homeostasis in plants and responses to such stresses, especially those imposed by arsenic and cadmium. We consider recent progress in understanding the regulation of biosynthesis of glutathione and phytochelatins and of the sensing mechanism of sulfur homeostasis for tolerance of trace metals and metalloids in plants. We also discuss the roles of glutathione and phytochelatins in controlling the accumulation and distribution of arsenic and cadmium in plants, and possible strategies for manipulating sulfur metabolism to limit their accumulation in food crops.
Asunto(s)
Arsénico , Metaloides , Humanos , Cadmio/metabolismo , Arsénico/metabolismo , Metaloides/metabolismo , Fitoquelatinas/metabolismo , Glutatión/metabolismo , Productos Agrícolas/metabolismo , Azufre/metabolismoRESUMEN
Metal-organic frameworks (MOFs) have attracted considerable attention as emerging nanomaterials. Based on their tunable size, high porosity, and large specific surface area, MOFs have a wide range of applications in the fields of chemistry, energy, and biomedicine. However, the MOF materials obtained from lanthanides with a unique electronic configuration as inorganic building units have unique properties such as optics, magnetism, and radioactivity. In this study, various synthetic methods for preparing MOF materials using lanthanides as inorganic building units are described. Combined with the characteristics of lanthanides, their application prospects of lanthanide-based MOFs in tumor diagnosis and treatment are emphasized. The authors hope to provide methodological reference for the construction of MOF materials of rare-earth elements, and to provide ideas and inspiration for their practical applications in the field of biomedicine.
Asunto(s)
Elementos de la Serie de los Lantanoides , Estructuras Metalorgánicas , Nanoestructuras , Neoplasias , Estructuras Metalorgánicas/uso terapéutico , Elementos de la Serie de los Lantanoides/uso terapéutico , Electrónica , Nanoestructuras/uso terapéutico , Porosidad , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMEN
Tumor-targeted delivery of antitumor drugs is considered a promising strategy for improving the chemotherapeutic efficiency and reducing the incidence of side effects. The development of tumor-targeted aptamers to accommodate drugs has attracted great interest because of their convenience in biomedical applications. CD133 is a robust biomarker of colorectal cancer. In this study, Cs5, a novel specific aptamer with a dissociation constant in the nanomolar range, was developed using the cell-SELEX strategy from engineered CD133-expressing cells, and doxorubicin (Dox) was loaded into the Cs5 aptamer to form a chimera. The chimera showed an excellent targeting ability for CD133 through a selective killing effect in human colorectal cancer HCT116 cells expressing CD133. The in vitro and in vivo results demonstrated the highly efficient therapy and low toxicity of the chimera. Given the overexpression of CD133 in various tumors, our work provides a promising tool for specific cell identification and a wide range of applications in the field of targeted cancer therapy.
Asunto(s)
Aptámeros de Nucleótidos , Neoplasias Colorrectales , Antígeno AC133/inmunología , Aptámeros de Nucleótidos/genética , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Doxorrubicina , Sistemas de Liberación de Medicamentos/métodos , HumanosRESUMEN
The biosynthesis of many sulfur-containing molecules depends on cysteine as a sulfur source. Both the cysteine desulfurase (CD) and rhodanese (Rhd) domain-containing protein families participate in the trafficking of sulfur for various metabolic pathways in bacteria and human, but their connection is not yet described in plants. The existence of natural chimeric proteins containing both CD and Rhd domains in specific bacterial genera, however, suggests a general interaction between these proteins. We report here the biochemical relationships between two cytosolic proteins from Arabidopsis thaliana, a Rhd domain-containing protein, the sulfurtransferase 18 (STR18), and a CD isoform referred to as ABA3, and compare these biochemical features to those of a natural CD-Rhd fusion protein from the bacterium Pseudorhodoferax sp. We observed that the bacterial enzyme is bifunctional exhibiting both CD and STR activities using l-cysteine and thiosulfate as sulfur donors but preferentially using l-cysteine to catalyze transpersulfidation reactions. In vitro activity assays and mass spectrometry analyses revealed that STR18 stimulates the CD activity of ABA3 by reducing the intermediate persulfide on its catalytic cysteine, thereby accelerating the overall transfer reaction. We also show that both proteins interact in planta and form an efficient sulfur relay system, whereby STR18 catalyzes transpersulfidation reactions from ABA3 to the model acceptor protein roGFP2. In conclusion, the ABA3-STR18 couple likely represents an uncharacterized pathway of sulfur trafficking in the cytosol of plant cells, independent of ABA3 function in molybdenum cofactor maturation.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Azufre , Arabidopsis/enzimología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Liasas de Carbono-Azufre , Cisteína/metabolismo , Citosol/metabolismo , Dominios Proteicos , Azufre/metabolismo , Sulfurtransferasas/metabolismo , Tiosulfato Azufretransferasa/genética , Tiosulfato Azufretransferasa/metabolismoRESUMEN
Neurons communicate through complex chemical and electrophysiological signal patterns to develop a tight information network. A physiological or pathological event cannot be explained by signal communication mode. Therefore, dual-mode electrodes can simultaneously monitor the chemical and electrophysiological signals in the brain. They have been invented as an essential tool for brain science research and brain-computer interface (BCI) to obtain more important information and capture the characteristics of the neural network. Electrochemical sensors are the most popular methods for monitoring neurochemical levels in vivo. They are combined with neural microelectrodes to record neural electrical activity. They simultaneously detect the neurochemical and electrical activity of neurons in vivo using high spatial and temporal resolutions. This paper systematically reviews the latest development of neural microelectrodes depending on electrode materials for simultaneous in vivo electrochemical sensing and electrophysiological signal recording. This includes carbon-based microelectrodes, silicon-based microelectrode arrays (MEAs), and ceramic-based MEAs, focusing on the latest progress since 2018. In addition, the structure and interface design of various types of neural microelectrodes have been comprehensively described and compared. This could be the key to simultaneously detecting electrochemical and electrophysiological signals.
Asunto(s)
Encéfalo , Neuronas , Microelectrodos , Encéfalo/fisiología , Neuronas/fisiologíaRESUMEN
Rice grains typically contain high levels of toxic arsenic but low levels of the essential micronutrient selenium. Anthropogenic arsenic contamination of paddy soils exacerbates arsenic toxicity in rice crops resulting in substantial yield losses. Here, we report the identification of the gain-of-function arsenite tolerant 1 (astol1) mutant of rice that benefits from enhanced sulfur and selenium assimilation, arsenic tolerance, and decreased arsenic accumulation in grains. The astol1 mutation promotes the physical interaction of the chloroplast-localized O-acetylserine (thiol) lyase protein with its interaction partner serine-acetyltransferase in the cysteine synthase complex. Activation of the serine-acetyltransferase in this complex promotes the uptake of sulfate and selenium and enhances the production of cysteine, glutathione, and phytochelatins, resulting in increased tolerance and decreased translocation of arsenic to grains. Our findings uncover the pivotal sensing-function of the cysteine synthase complex in plastids for optimizing stress resilience and grain quality by regulating a fundamental macronutrient assimilation pathway.
Asunto(s)
Arsénico/metabolismo , Oryza/metabolismo , Semillas/metabolismo , Selenio/metabolismo , Azufre/metabolismo , Alelos , Cloroplastos/metabolismo , Cisteína Sintasa/metabolismo , Redes y Vías Metabólicas , Modelos Biológicos , Mutación/genética , Fenotipo , Fitoquelatinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Serina/metabolismo , Fracciones Subcelulares/metabolismoRESUMEN
Arsenic (As) contamination in paddy soil can cause phytotoxicity and elevated As accumulation in rice grains. Arsenic detoxification is closely linked to sulfur assimilation, but the genes involved have not been described in rice. In this study, we characterize the function of OASTL-A1, an O-acetylserine(thiol) lyase, in cysteine biosynthesis and detoxification of As in rice. Tissue expression analysis revealed that OsOASTL-A1 is mainly expressed in roots at the vegetative growth stage and in nodes at the reproductive stage. Furthermore, the expression of OsOASTL-A1 in roots was strongly induced by As exposure. Transgenic rice plants expressing pOsOASTL-A1::GUS (ß-glucuronidase) indicated that OsOASTL-A1 was strongly expressed in the outer cortex and the vascular cylinder in the root mature zone. Subcellular localization using OsOASTL-A1:eGFP (enhanced green fluorescent protein) fusion protein showed that OsOASTL-A1 was localized to the cytosol. In vivo and in vitro enzyme activity assays showed that OsOASTL-A1 possessed the O-acetylserine(thiol) lyase activity. Knockout of OsOASTL-A1 led to significantly lower levels of cysteine, glutathione, and phytochelatins in roots and increased sensitivity to arsenate stress. Furthermore, the osoastl-a1 knockout mutants reduced As accumulation in the roots, but increased As accumulation in shoots. We conclude that OsOASTL-A1 is the cytosolic O-acetylserine(thiol) lyase that plays an important role in non-protein thiol biosynthesis in roots for As detoxification.
Asunto(s)
Arsénico , Oryza , Arsénico/toxicidad , Cisteína , Cisteína Sintasa/genética , Citosol , Oryza/genética , Raíces de PlantasRESUMEN
Lung cancer is one of the leading causes of tumorassociated mortality, and >75% of patients with lung cancer have nonsmall cell lung cancer (NSCLC). Pemetrexed, a folate antagonist, is a firstline chemotherapy drug for NSCLC that is administered alone or in combination with cisplatin. The present study established in vitro cell models of PTEN inhibition and overexpression, and the effects of the treatment with pemetrexed were investigated in these cell models. Result from the present study demonstrated that treatment with pemetrexed suppressed lung cancer cell proliferation, inhibited mRNA and protein expression levels of antiapoptotic Bcl2, and increased the mRNA and the protein expression levels of proapoptotic p53 and apoptosis regulator BAX. The present study suggested that pemetrexed regulated apoptosis via the inhibition of the mTOR/PI3K/AKT signaling pathway. Additionally, cellular processes associated with the aerobic oxidation of carbohydrates were identified to be significantly inhibited. The present findings suggested that treatment with pemetrexed may exhibit synergistic effects with PTEN on lung cancer cells via the inhibition of the PI3K/AKT/mTOR signaling pathway and through carbohydrate metabolism, and treatment with pemetrexed combined with PTEN overexpression may represent a novel therapeutic strategy for the treatment of NSCLC.
Asunto(s)
Antineoplásicos/farmacología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Fosfohidrolasa PTEN/genética , Pemetrexed/farmacología , Transducción de Señal/efectos de los fármacos , Células A549 , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: Casein kinase 2 interacting protein-1 (CKIP-1) has exhibited multiple functions in regulating cell proliferation, apoptosis, differentiation, and cytoskeleton. CKIP-1 also plays an important role as a critical regulator in tumorigenesis. The aim of this study is to further examine the function of CKIP-1 in glioma cells. METHODS: The expression level of CKIP-1 protein was determined in gliomas tissues and cell lines by immunohistochemistry stain and western blotting while the association of CKIP-1 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. CKIP-1 was overexpressed or silenced in gliomas cell lines. CCK-8, colony formation assay, and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis. Cell cycle and apoptosis rate were determined with fluorescence-activated cell sorting (FACS) method. Then, expression of key members in AKT/GSK3ß/ß-catenin pathway was detected by western blot analysis. RESULTS: In the present study, we reported new evidence that CKIP-1 was reversely associated with the proliferation of glioma cells and survival in glioma patients. Additionally, the overexpressed CKIP-1 significantly inhibited glioma cell proliferation. Further experiments revealed that CKIP-1 functioned through its antiproliferative and proapoptotic activity in glioma cells. Importantly, mechanistic investigations suggested that CKIP-1 sharply suppressed the activity of AKT by inhibiting the phosphorylation, markedly downregulated the phosphorylated GSK3ß at Ser9, and promoted ß-catenin degradation. CONCLUSIONS: Overall, our results provided new insights into the clinical significance and molecular mechanism of CKIP-1 in glioma, which indicated CKIP1 might function as a therapeutic target for clinical treatment of glioma.
Asunto(s)
Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioma , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , beta Catenina/metabolismo , Adulto , Línea Celular Tumoral , Femenino , Glioma/metabolismo , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Liver cancer is the fifth most commonly occurring cancer in men and the ninth most commonly occurring cancer in women, worldwide, and is associated with a high mortality rate. Sorafenib is a new inhibitor of multiple kinases, that is regarded as standard treatment for liver cancer. Human breast carcinoma metastasissuppressor 1 (BRMS1) is a tumorsuppressor gene, that reduces the metastatic ability of tumor cells without affecting their tumorigenicity. In the present study, a model of BRMS1 overexpression and BRMS1 knockdown was established in HepG2 cells. The results revealed that the proliferation of HepG2 cells was inhibited in response to sorafenib treatment using MTT assay. Furthermore, BRMS1 overexpression enhanced the effect of sorafenib. In addition, expression of inflammatory responserelated genes was increased, while secretion of angiogenesisrelated molecules was decreased, and apoptosis was also activated after sorafenib treatment using qPCR method, and it was further demonstrated that this effect was mediated by inhibition of the PI3K/AKT/mTOR/ERK signaling pathway using western blot analysis. In conclusion, overexpression of BRMS1 potentiated the effect of sorafenib via PI3K/AKT/mTOR/ERK signaling, while knockdown of BRMS1 expression attenuated this effect. These findings may present a novel therapeutic strategy for liver cancer.
Asunto(s)
Carcinoma Hepatocelular/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/metabolismo , Sorafenib/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Sinergismo Farmacológico , Quinasas MAP Reguladas por Señal Extracelular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Represoras/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Células Tumorales CultivadasRESUMEN
It has been verified that long noncoding RNAs (lncRNAs) have great effects on various biological behaviors of human diseases. Although more and more lncRNAs have been studied in human cancers, countless lncRNAs still need to be excavated. This study aims to investigate the impacts of lncRNA SNHG16 on proliferation and metastasis of human hemangioma endothelial cell (HemECs). qRT-PCR analysis was carried out to explore the expression pattern of SNHG16, miR-520d-3p, and STAT3. The effect of SNHG16 on cell proliferation was detected by MTT and colony formation assay. Flow cytometry analysis was performed to test the apoptosis of HemECs cells. Migration and invasion of HemECs cells were determined and examined by transwell assays. Tube formation assay helped to observe the influence of SNHG16 expression on the vasoformation of HemECs cells. The correlations among SNHG16, miR-520d-3p, and STAT3 were certified by bioinformatics analysis, pull-down assay, and dual-luciferase reporter assay. Finally, rescue assays were conducted to demonstrate the effects of SNHG16-miR-520d-3p-STAT3 axis on biological behaviors of HemECs cell. SNHG16 was strongly expressed in proliferating phase hemangioma tissues and HemECs cells. Silenced SNHG16 negatively affected proliferation, migration, and invasion of HemECs cell. LncRNA SNHG16 acted as a ceRNA to upregulate STAT3 through binding with miR-520d-3p in HemECs cell. LncRNA SNHG16 acted as a ceRNA to drive proliferation, vasoformation, migration, and invasion of HemECs cells through modulating miR-520d-3p/STAT3 axis.
RESUMEN
Rice is a major dietary source of the toxic metalloid arsenic. Reducing arsenic accumulation in rice grain is important for food safety. We generated transgenic rice overexpressing two aquaporin genes, OsNIP1;1 and OsNIP3;3, under the control of a maize ubiquitin promoter or the rice OsLsi1 promoter, and tested the effect on arsenite uptake and translocation. OsNIP1;1 and OsNIP3;3 were highly permeable to arsenite in Xenopus oocyte assays. Both transporters were localized at the plasma membrane. Knockout of either gene had little effect on arsenite uptake or translocation. Overexpression of OsNIP1;1 or OsNIP3;3 in rice did not affect arsenite uptake but decreased root-to-shoot translocation of arsenite and shoot arsenic concentration markedly. The overexpressed OsNIP1;1 and OsNIP3;3 proteins were localized in all root cells without polarity. Expression of OsNIP1;1 driven by the OsLsi1 promoter produced similar effects. When grown in two arsenic-contaminated paddy soils, overexpressing lines contained significantly lower arsenic concentration in rice grain than the wild-type without compromising plant growth or the accumulation of essential nutrients. Overexpression of OsNIP1;1 or OsNIP3;3 provides a route for arsenite to leak out of the stele, thus restricting arsenite loading into the xylem. This strategy is effective in reducing arsenic accumulation in rice grain.
Asunto(s)
Arsénico/metabolismo , Arsenitos/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Transporte Biológico , Permeabilidad de la Membrana Celular , Regulación de la Expresión Génica de las Plantas , Técnicas de Inactivación de Genes , Especificidad de Órganos/genética , Oryza/crecimiento & desarrollo , Proteínas de Plantas/genética , Brotes de la Planta/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética , Silicio/metabolismo , Xilema/metabolismoRESUMEN
Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI). C57BL/6 mice underwent lateral fluid percussion TBI. TBI mice were transfected with a lentivirus carrying the DCX-ChR2-EGFP gene. We observed that not only immature neurons but also type-2b intermediate progenitor (IPs) and neuroblasts expressed DCX-EGFP, indicating that DCX-expressing newborn cells could provide a long time window for electrical activity regulation. Quantitative results showed that the number of EGFP-expressing cells began to rise at 3 days after TBI and peaked at 9 days after TBI. By optical depolarization of DCX-EGFP-expressing cells between 3 and 12 days, we observed significantly improved cognitive deficits after TBI with enhanced survival and maturation of newborn cells in the dentate gyrus. We also investigated the role of optical depolarization in neural stem cells transfected with a lentivirus carrying the ChR2-DCX-EGFP gene in vitro. By administrating verapamil to block L-type calcium channels, we verified that the up-regulation of MAP2, NeuN, Neurog2, NeuroD1 and GluR2 in newborn cells was mediated by ChR2-elicted depolarization. By using ß-catenin inhibitor Dkk1, we demonstrated that optical depolarization of DCX-EGFP-expressing cells facilitated survival and maturation probably through the Wnt/ß-catenin signaling cascade.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Trastornos del Conocimiento/etiología , Proteínas Asociadas a Microtúbulos/metabolismo , Neurogénesis/fisiología , Neuropéptidos/metabolismo , Recuperación de la Función/fisiología , Vía de Señalización Wnt/fisiología , Potenciales de Acción/fisiología , Factores de Edad , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Bromodesoxiuridina/metabolismo , Células Cultivadas , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Embrión de Mamíferos , Hipocampo/citología , Técnicas In Vitro , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/genética , Proteínas del Tejido Nervioso/metabolismo , Células-Madre Neurales/fisiología , Neuronas/fisiología , Neuropéptidos/genética , Optogenética , Transducción GenéticaRESUMEN
Previous studies have shown that the Nodulin 26-like intrinsic membrane protein (NIP) Lsi1 (OsNIP2;1) is involved in arsenite [As(III)] uptake in rice (Oryza sativa). However, the role of other rice NIPs in As(III) accumulation in planta remains unknown. In the present study, we investigated the role OsNIP3;2 in As(III) uptake in rice. When expressed in Xenopus laevis oocytes, OsNIP3;2 showed a high transport activity for As(III). Quantitative real-time RT-PCR showed that the expression of OsNIP3;2 was suppressed by 5 µM As(III), but enhanced by 20 and 100 µM As(III). Transgenic rice plants expressing OsNIP3;2pro-GUS showed that the gene was predominantly expressed in the lateral roots and the stele region of the primary roots. Transient expression of OsNIP3;2:GFP fusion protein in rice protoplasts showed that the protein was localized in the plasma membrane. Knockout of OsNIP3;2 significantly decreased As concentration in the roots, but had little effect on shoot As concentration. Synchrotron microfocus X-ray fluorescence showed decreased As accumulation in the stele of the lateral roots in the mutants compared with wild-type. Our results indicate that OsNIP3;2 is involved in As(III) uptake by lateral roots, but its contribution to As accumulation in the shoots is limited.
Asunto(s)
Arsenitos/metabolismo , Proteínas de la Membrana/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Animales , Proteínas de la Membrana/química , Mutación , Oryza/genética , Proteínas de Plantas/química , Plantas Modificadas Genéticamente , Proteínas Recombinantes/metabolismo , Ácido Silícico/metabolismo , Xenopus laevisRESUMEN
OBJECTIVE: To conduct a meta-analysis of available comparative studies evaluating hybrid arch repair versus open surgical repair of aortic arch aneurysm. METHODS: A literature search was performed using PubMed, Embase and Web of Science to identify any studies comparing the results of hybrid arch repair with open surgical repair of aortic arch aneurysm. Study quality was assessed with the Newcastle-Ottawa Scale. Statistical heterogeneity was estimated using the chi-square test. A random-effects model was used to illustrate heterogeneity. Publication bias was evaluated by funnel plots. RESULTS: Seven retrospective cohort studies from 2009 to 2016 comprising 727 patients were included. Among these patients, 269 were treated with hybrid arch repair and 458 with open surgical repair. There was no significant difference in operative mortality (OR 0.75; 95% CI 0.41-1.39; P = 0.37), permanent neurological deficit (OR 1.24; 95% CI 0.73-2.13; P = 0.42), late mortality (2 years) (OR 3.41; 95% CI 0.83-14.03; P = 0.09) or renal failure (OR 0.80; 95% CI 0.40-1.61; P = 0.53). Interestingly, the meta-analysis indicated that the hybrid group needed more reinterventions (OR 3.43; 95% CI 1.72-6.84; P = 0.0005). CONCLUSIONS: We found no strong evidence indicating that hybrid arch repair is superior to open surgical repair. Furthermore, the hybrid arch repair resulted in more reinterventions despite the fact that it was a less invasive procedure; it also required fewer days in the hospital. Further studies with large numbers of participants and long-term follow-ups are necessary to confirm the effectiveness of hybrid arch repair.
Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Stents , Resultado del TratamientoRESUMEN
Silver nanoparticles (Ag-NPs) are used in a wide range of everyday products, leading to increasing concerns regarding their accumulation in soils and subsequent impact on plants. Using single particle inductively coupled plasma mass spectrometry (spICP-MS) and synchrotron-based techniques including X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM), we characterized the uptake, speciation, and translocation of insoluble Ag2S-NPs (an environmentally-relevant form of Ag-NPs in soils) within two plant species, a monocot and a dicot. Exposure to 10 mg Ag L-1 as Ag2S-NPs for one week resulted in a substantial increase in leaf Ag concentrations (3.8 to 5.8 µg Ag g-1 dry mass). Examination using XAS revealed that most of the Ag was present as Ag2S (>91%). Furthermore, analyses using spICP-MS confirmed that these Ag2S particles within the leaves had a markedly similar size distribution to those supplied within the hydroponic solution. These observations, for the first time, provide direct evidence that plants take up Ag2S-NPs without a marked selectivity in regard to particle size and without substantial transformation (dissolution or aggregation) during translocation from roots to shoots. Furthermore, after uptake, these Ag2S-NPs reduced growth, partially due to the solubilisation of Ag+ in planta, which resulted in an upregulation of genes involved in the ethylene signalling pathway. Additionally, the upregulation of the plant defense system as a result of Ag2S-NPs exposure may have contributed to the decrease in plant growth. These results highlight the risks associated with Ag-NP accumulation in plants and subsequent trophic transfer via the food chain.