RESUMEN
Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.
Asunto(s)
Vesículas Extracelulares , Mitocondrias , Medicina Regenerativa , Humanos , Vesículas Extracelulares/metabolismo , Medicina Regenerativa/métodos , Mitocondrias/metabolismo , AnimalesRESUMEN
The WRKY transcription factor (TF) genes form a large family in higher plants, with 72 members in Arabidopsis (Arabidopsis thaliana). The gaseous phytohormone ethylene (ET) regulates multiple physiological processes in plants. It is known that 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACSs, EC 4.4.1.14) limit the enzymatic reaction rate of ethylene synthesis. However, whether WRKY TFs regulate the expression of ACSs and/or ACC oxidases (ACOs, EC 1.14.17.4) remains largely elusive. Here, we demonstrated that Arabidopsis WRKY22 positively regulated the expression of a few ACS and ACO genes, thus promoting ethylene production. Inducible overexpression of WRKY22 caused shorter hypocotyls without ACC treatment. A qRT-PCR screening demonstrated that overexpression of WRKY22 activates the expression of several ACS and ACO genes. The promoter regions of ACS5, ACS11, and ACO5 were also activated by WRKY22, which was revealed by a dual luciferase reporter assay. A follow-up chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assay (EMSA) showed that the promoter regions of ACS5 and ACO5 could be bound by WRKY22 directly. Moreover, wrky22 mutants had longer primary roots and more lateral roots than wild type, while WRKY22-overexpressing lines showed the opposite phenotype. In conclusion, this study revealed that WRKY22 acts as a novel TF activating, at least, the expression of ACS5 and ACO5 to increase ethylene synthesis and modulate root development.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Etilenos , Regulación de la Expresión Génica de las Plantas , Liasas , Raíces de Plantas , Factores de Transcripción , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Etilenos/metabolismo , Etilenos/biosíntesis , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Liasas/genética , Liasas/metabolismo , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Regiones Promotoras Genéticas/genética , Liasas de Carbono-Carbono/metabolismo , Liasas de Carbono-Carbono/genética , Activación Transcripcional/genéticaRESUMEN
The main challenges faced by aqueous rechargeable nickel-zinc batteries are their comparatively low energy density and poor cycling stability. Moreover, the preparation procedures of these cathodes are complex and not easily scalable. Herein, we utilized MXene to improve the electrodeposition preparation of NiCo layered double hydroxides (LDH). Benefiting from the improved interfacial contact between nickel foam (NF) and platting solution and the enhanced ionic conductivity of platting product based on MXene additives, the resulting binder-free NiCo LDH electrode can achieve ultrahigh areal loading (~65 mg cm-2) with abundant active surface for redox reactions and maintained short transport pathway for ion diffusion and charge transfer. Furthermore, the as-fabricated alkaline NiCo LDH-based battery delivers high discharge capacity, up to 20.2 mAh cm-2 (311 mAh g-1), accompanied by remarkable rate performance (9.6 mAh cm-2 or 148 mAh g-1 at 120 mA cm-2). Due to the high structural and chemical stability of MXenes/LDH-based electrode, excellent cycling life can also be achieved with 88.6% capacity retention after 10000 cycles. In addition, ultrahigh areal energy density (31.2 mWh cm-2) and gravimetric energy density (465 Wh kg-1) can be simultaneously achieved. This work has inspired the design of advanced cathode materials to develop high-performance aqueous zinc batteries.
RESUMEN
Chalcogens, especially tellurium (Te), as conversion-type cathodes possess promising prospects for zinc batteries (ZBs) with potential rich valence supply and high energy density. However, the conversion reaction of Te is normally restricted to the Te2-/Te0 redox with a low voltage plateau at â¼0.59 V (vs Zn2+/Zn) rather than the expected positive valence conversion of Te0 to Ten+, inhibiting the development of Te-based batteries toward high output voltage and energy density. Herein, the desired reversible Te2-/Te0/Te2+/Te4+ redox behavior with up to six-electron transfer was successfully activated by employing a highly concentrated Cl--containing electrolyte (Cl- as strong nucleophile) for the first time. Three flat discharge plateaus located at 1.24, 0.77, and 0.51 V, respectively, are attained with a total capacity of 802.7 mAh g-1. Furthermore, to improve the stability of Ten+ products and enhance the cycling stability, a modified ionic liquid (IL)-based electrolyte was fabricated, leading to a high-performance Znâ¥Te battery with high areal capacity (7.13 mAh cm-2), high energy density (542 Wh kgTe-1 or 227 Wh Lcathdoe+anode-1), excellent cycling performance, and a low self-discharge rate based on 400 mAh-level pouch cell. The results enhance the understanding of tellurium chemistry in batteries, substantially promising a remarkable route for advanced ZBs.
RESUMEN
Reactive oxygen species (ROS) and salicylic acid (SA) are two factors regulating leaf senescence and defense against pathogens. However, how a single gene integrates both ROS and SA pathways remains poorly understood. Here, we show that Arabidopsis WRKY55 transcription factor positively regulates ROS and SA accumulation, and thus leaf senescence and resistance against the bacterial pathogen Pseudomonas syringaeWRKY55 is predominantly expressed in senescent leaves and encodes a transcriptional activator localized to nuclei. Both inducible and constitutive overexpression of WRKY55 accelerates leaf senescence, whereas mutants delay it. Transcriptomic sequencing identified 1448 differentially expressed genes, of which 1157 genes are upregulated by WRKY55 expression. Accordingly, the ROS and SA contents in WRKY55-overexpressing plants are higher than those in control plants, whereas the opposite occurs in mutants. Moreover, WRKY55 positively regulates defense against P. syringae Finally, we show that WRKY55 activates the expression of RbohD, ICS1, PBS3 and SAG13 by binding directly to the W-box-containing fragments. Taken together, our work has identified a new WRKY transcription factor that integrates both ROS and SA pathways to regulate leaf senescence and pathogen resistance.
Asunto(s)
Proteínas de Arabidopsis/biosíntesis , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ácido Salicílico/metabolismo , Factores de Transcripción/biosíntesis , Arabidopsis/genética , Arabidopsis/microbiología , Proteínas de Arabidopsis/genética , Enfermedades de las Plantas/microbiología , Hojas de la Planta/genética , Hojas de la Planta/microbiología , Pseudomonas syringae , Factores de Transcripción/genéticaRESUMEN
Autophagy is an important mechanosensitive response for cellular homeostasis and survival in osteocytes. However, the mechanism and its effect on bone metabolism have not yet clarified. The objective of this study was to evaluate how compressive cyclic force (CCF) induced autophagic response in osteocytes and to determine the effect of mechanically induced-autophagy on bone cells including osteocytes, osteoblasts, and osteoclasts. Autophagic puncta observed in MLO-Y4 cells increased after exposure to CCF. The upregulated levels of the LC3-II isoform and the degradation of p62 further confirmed the increased autophagic flux. Additionally, ATP synthesis and release, osteocalcin (OCN) expression, and cell survival increased in osteocytes as well. The Murine osteoblasts MC3T3-E1 cells and RAW 264.7 macrophage cells were cultured in conditioned medium collected from MLO-Y4 cells subjected to CCF. The concentration of FGF23 increased and the concentrations of SOST and M-CSF and RANKL/OPG ratio decreased significantly in the conditioned medium. Moreover, the promotion of osteogenic differentiation in MC3T3-E1 cells and inhibition of osteoclastogenesis and function in RAW 264.7 cells were significantly attenuated when osteocytes autophagy was inhibited by siAtg7. Our findings suggested that CCF induced protective autophagy in osteocytes and subsequently enhanced osteocytes survival and osteoblasts differentiation and downregulated osteoclasts activities. Further study revealed that CCF induced autophagic response in osteocytes through mechanistic target of rapamycin complex 2 (mTORC2) activation. In conclusion, CCF-induced osteocytes autophagy upon mTORC2 activation promoted osteocytes survival and osteogenic response and decreased osteoclastic function. Thus, osteocytes autophagy will provide a promising target for better understanding of bone physiology and treatment of bone diseases.
Asunto(s)
Diana Mecanicista del Complejo 2 de la Rapamicina , Osteoclastos , Osteogénesis , Animales , Ratones , Autofagia , Diferenciación Celular , Medios de Cultivo Condicionados/metabolismo , Medios de Cultivo Condicionados/farmacología , Osteoblastos , Osteoclastos/metabolismo , Osteocitos/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Células RAW 264.7RESUMEN
The weak electron-hole separation ability and the more severe photocorrosion of CdS largely limit its hydrogen precipitation performance. In this study, CoP loading on the surface of CdS was utilized to form a type I heterojunction. The photocurrent density increased from 2 µA cm-2 to 20 µA cm-2. When the loading of CoP was 10%, the best photocatalytic performance reached 4.43 mmolg-1 h-1 under visible light, which was 20.1 times higher than that of CdS (0.22 mmolg-1 h-1). In addition, the loading of CoP solved the problem of CdS photocorrosion. After 5 cycles of simulated solar irradiation, the performance of 10% CoP/CdS remained at 93% of the initial test. This work provides new ideas for the design of low photocorrosion and high-performance catalysts.
RESUMEN
Electrolyte environments, including cations, anions, and solvents are critical for the performance delivery of cathodes of batteries. Most works focused on interactions between cations and cathode materials, in contrast, there is a lack of in-depth research on the correlation between anions and cathodes. Here, we systematically investigated how anions manipulate the coulombic efficiency (CE) of cathodes of zinc batteries. We take intercalation-type V2 O5 and conversion-type I2 cathodes as typical cases for profound studies. It was found that electronic properties of anions, including charge density and its distribution, can tune conversion or intercalation reactions, leading to significant CE differences. Using operando visual Raman microscopy and theoretical simulations, we confirm that competitive coordination between anions and I- can regulate CEs by modulating polyiodide diffusion rates in Zn-I2 cells. In Zn-V2 O5 cells, anion-tuned solvation structures vastly affect CEs through varying Zn2+ intercalation kinetics. Conversion I2 cathode achieves a 99 % CE with highly electron-donating anions, while anions with preferable charge structures that interact strongly with Zn2+ afford an intercalation V2 O5 a nearly 100 % CE. Understanding the mechanism of anion-governed CEs will help us evaluate compatibility of electrolytes with electrodes, thus providing a guideline for anion selection and electrolyte design for high-energy, long-cycling zinc batteries.
RESUMEN
A liquid simulated eye was designed to detect different spherical diopter indexes in the type inspection of medical equipment vision screening instrument. This liquid test simulation eye design is composed of three parts: lens, cavity and retina-imitation piston. By using the principle of geometric optics and the optical scattering effect of human retina, the relationship between the accommodation displacement of the designed adjustable liquid simulated eye and the spherical mirror power was calculated and analyzed. The designed liquid test simulated eye can be applied to vision screening instruments, computer refractometers and other optometry equipments based on photography principle in spherical lens measurement and so on.
Asunto(s)
Cristalino , Selección Visual , Humanos , Visión Ocular , Retina , FotograbarRESUMEN
Indocyanine green (ICG) is the most commonly used near-infrared fluorescent (NIRF) dye in clinical practice, and its mediated near-infrared fluorescence imaging technology is gradually applied in clinical practice. It has shown great potential in invasive surgery (MIS) and is expected to become the standard technology for surgical diagnosis and treatment of diseases. The clinical application of ICG fluorescence laparoscopy is reviewed here.
Asunto(s)
Verde de Indocianina , Laparoscopía , Fluorescencia , ColorantesRESUMEN
The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 also controls the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin 3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator that is crucial for specifying a generic PSN type identity after neurogenesis is later regulated by target muscle-derived signals to contribute to the specialized aspects of the sensorimotor connection selectivity.
Asunto(s)
Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Células Cultivadas , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Femenino , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Neuronas Motoras/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Células Receptoras Sensoriales/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Sodium (Na+ ) is the major cation damaging crops in the salinised farmland. Previous studies have shown that the Salt Overly Sensitive (SOS) pathway is important for salt tolerance in Arabidopsis. Nevertheless, the SOS pathway remains poorly investigated in most crops. This study addresses the function of the SOS pathway and its association with the natural variation of salt tolerance in maize. First, we showed that a naturally occurring 4-bp frame-shifting deletion in ZmSOS1 caused the salt hypersensitive phenotype of the maize inbred line LH65. Accordingly, mutants lacking ZmSOS1 also displayed a salt hypersensitive phenotype, due to an impaired root-to-rhizosphere Na+ efflux and an increased shoot Na+ concentration. We next showed that the maize SOS3/SOS2 complex (ZmCBL4/ZmCIPK24a and ZmCBL8/ZmCIPK24a) phosphorylates ZmSOS1 therefore activating its Na+ -transporting activity, with their loss-of-function mutants displaying salt hypersensitive phenotypes. Moreover, we observed that a LTR/Gypsy insertion decreased the expression of ZmCBL8, thereby increasing shoot Na+ concentration in natural maize population. Taken together, our study demonstrated that the maize SOS pathway confers a conservative salt-tolerant role, and the components of SOS pathway (ZmSOS1 and ZmCBL8) confer the natural variations of Na+ regulation and salt tolerance in maize, therefore providing important gene targets for breeding salt-tolerant maize.
Asunto(s)
Arabidopsis , Tolerancia a la Sal , Arabidopsis/genética , Fitomejoramiento , Tolerancia a la Sal/genética , Sodio/metabolismo , Zea mays/metabolismoRESUMEN
OBJECTIVE: The tibial toddler's fracture is an important diagnosis in both emergency and urgent care, presenting as acute onset lower extremity pain or limping in a young child. Diagnosis and management may be challenging because of an extensive differential diagnosis. The objectives of this study were to provide an overview of the toddler's fracture and to guide clinicians by summarizing up to date literature for both diagnosis and management this common condition. METHODS: This study analyzed literature from the PubMed database from the years of 1964 to 2018. The main focus was on the diagnosis and management of the toddler's fracture. RESULTS: This review demonstrates that diagnosis is primarily made through history and physical examination, as radiographs are often negative at initial presentation. Treatment involves a short period of immobilization, which can be facilitated through the use of a cast, a splint, or no external support. Successful healing and a full return to normal activities and development are near universal. CONCLUSIONS: Although a stable fracture with an excellent prognosis, opportunities exist to improve toddler's fractures diagnosis and treatment protocols, to optimize clinical management.
Asunto(s)
Fracturas de la Tibia , Humanos , Lactante , Examen Físico , Pronóstico , Radiografía , Férulas (Fijadores) , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/terapiaRESUMEN
STATEMENT OF PROBLEM: The influence of surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramics (ZLS) is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effect of different surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramic after long-term thermocycling. MATERIAL AND METHODS: Five computer-aided design and computer-aided manufacturing (CAD-CAM) dental ceramic blocks, including 2 zirconia-reinforced lithium silicate ceramic materials (Vita Suprinity/VS and Cetra Duo/CD), 2 commonly used glass-ceramic materials (e.max CAD/EM and Empress CAD/EP), and 1 yttria-stabilized zirconia (Y-TZP, Zenostar/ZS) were tested. Rectangular ceramic blocks were divided into 6 groups and subjected to different surface treatments: group Control (no treatment), group Uni (universal adhesive), group HF (hydrofluoric acid), group CoJet, group HF+Uni (HF and universal adhesive), and group CoJet+Uni (CoJet and universal adhesive). Subsequently, the specimens were cemented to composite resin blocks, sectioned into rectangular microbars of approximately 2×2×12 mm in size, and assigned to 2 groups with and without 100 000 thermal cycles (n=15 per group). The microtensile bond strength (µTBS) test was performed using a universal testing machine. Failure modes were observed with a stereomicroscope and scanning electron microscope (SEM). Three-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons was performed to evaluate the effects of surface treatments, ceramics, and thermocycling on µTBS (α=.05). RESULTS: The µTBS (MPa) was affected by the surface treatment (P<.001), ceramic type (P<.001), and thermocycling (P<.001). The bond strength after HF etching and universal adhesive treatment was highest in glass-ceramic groups (VS, CD, EP, and EM), while CoJet combined with universal adhesive indicated the highest bond strength in the ZS group before (34.3 ±4.2 MPa) and after thermocycling (16.0 ±2.9 MPa). No significant differences for µTBS were found among ZLS (VS and CD), lithium disilicate ceramic group (EM), and leucite-based ceramic group (EP, P>.05), but they demonstrated better bond strength than zirconia (ZS group, P<.01) after thermocycling. Adhesive failure increased in all groups, and the cohesive failure of glass-ceramic decreased after thermocycling. CONCLUSIONS: ZLS showed similar µTBS with traditional glass-ceramics, including lithium disilicate ceramic and leucite-based ceramic, and more durable bonding than zirconia to resist thermocycling. Moreover, the combination of HF and universal adhesive treatments was the most effective method for ZLS among all the different surface treatments in this study.
Asunto(s)
Recubrimiento Dental Adhesivo , Litio , Cementos de Resina/química , Ensayo de Materiales , Propiedades de Superficie , Porcelana Dental/química , Circonio/química , Cerámica/química , SilicatosRESUMEN
Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.
Asunto(s)
Dexmedetomidina/farmacología , Hepatopatías/etiología , Hepatopatías/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Biomarcadores , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patologíaRESUMEN
At present, most of the reported planar pentacoordinate clusters are similar to the isoelectronic substitution of CAl5+, with 18 counting electrons. Meanwhile, the regular planar pentacoordinate boron systems are rarely reported. Hereby, a sulphur-bridged BAl5S5+ system with a five-pointed star configuration and 17 counting electrons is identified at the global energy minimum through the particle-swarm optimization method, based on the previous recognition on bridged sulphur as the peripheral tactics to the stable planar tetracoordinate carbon and boron. Its outstanding stability has been demonstrated by thermodynamic analysis at 900 K, electronic properties and chemical bonding analysis. This study provides adequately theoretical basis and referable data for its experimental capture and testing.
RESUMEN
BACKGROUND: Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. METHODS: Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. RESULTS: Ca signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 µg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, -0.745 [-1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 µg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, -0.498 [-0.664; -0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, -0.329 [-1.220; -0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 µg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). CONCLUSIONS: Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation.
Asunto(s)
Dexmedetomidina/farmacología , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Hipnóticos y Sedantes/farmacología , Área Tegmental Ventral/metabolismo , Animales , Neuronas Dopaminérgicas/química , Neuronas Dopaminérgicas/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Electroencefalografía/métodos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Técnicas de Cultivo de Órganos , Fotometría/métodos , Área Tegmental Ventral/química , Área Tegmental Ventral/efectos de los fármacosRESUMEN
BACKGROUND: Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18F-fluoromisonidazole (FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer (CRC) in mice. METHODS: Colorectal liver metastases (CRLM) xenograft models were established by injecting tumor cells (LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. 18F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. 18F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1α) and serum starvation-induced glucose transporter 1 (GLUT-1) was evaluated using Pearson correlation analysis. RESULTS: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, 18F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between 18F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5â¯cm, as well as between 18F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues. CONCLUSIONS: 18F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Misonidazol/análogos & derivados , Tomografía de Emisión de Positrones/métodos , Intensificación de Imagen Radiográfica , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Invasividad Neoplásica/patología , Distribución Aleatoria , Sensibilidad y Especificidad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
MAIN CONCLUSION: Overexpression of BnaWGR1 causes ROS accumulation and promotes leaf senescence. BnaWGR1 binds to promoters of RbohD and RbohF and regulates their expression. Manipulation of leaf senescence process affects agricultural traits of crop plants, including biomass, seed yield and stress resistance. Since delayed leaf senescence usually enhances tolerance to multiple stresses, we analyzed the function of specific MAPK-WRKY cascades in abiotic and biotic stress tolerance as well as leaf senescence in oilseed rape (Brassica napus L.), one of the important oil crops. In the present study, we showed that expression of one WRKY gene from oilseed rape, BnaWGR1, induced an accumulation of reactive oxygen species (ROS), cell death and precocious leaf senescence both in Nicotiana benthamiana and transgenic Arabidopsis (Arabidopsis thaliana). BnaWGR1 regulates the transcription of two genes encoding key enzymes implicated in production of ROS, that is, respiratory burst oxidase homolog (Rboh) D and RbohF. A dual-luciferase reporter assay confirmed the transcriptional regulation of RbohD and RbohF by BnaWGR1. In vitro electrophoresis mobility shift assay (EMSA) showed that BnaWGR1 could bind to W-box cis-elements within promoters of RbohD and RbohF. Moreover, RbohD and RbohF were significantly upregulated in transgenic Arabidopsis overexpressing BnaWGR1. In summary, these results suggest that BnaWGR1 could positively regulate leaf senescence through regulating the expression of RbohD and RbohF genes.
Asunto(s)
Brassica napus/genética , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Arabidopsis/citología , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Muerte Celular , Flores/genética , Flores/fisiología , Genes Reporteros , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética , Plantones/genética , Plantones/fisiología , Factores de Tiempo , Nicotiana/citología , Nicotiana/genética , Nicotiana/fisiología , Factores de Transcripción/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Positron emission tomography (PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of 18F-fludeoxyglucose (18F-FDG) and 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis. METHODS: The uptake rate of 18F-FDG and 18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio (tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression. RESULTS: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of 18F-FDG in SW480 and SW620 cells was 6.07%⯱â¯1.19% and 2.82%⯱â¯0.15%, respectively (tâ¯=â¯4.69, Pâ¯=â¯0.04); that of 18F-FLT was 24.81%⯱â¯0.45% and 15.57%⯱â¯0.66%, respectively (tâ¯=â¯19.99, Pâ¯<â¯0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and 18F-FLT uptake in primary tumors (râ¯=â¯0.73, Pâ¯=â¯0.0019). 18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases (râ¯=â¯0.81, Pâ¯=â¯0.0049). CONCLUSIONS: The uptake of 18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells. 18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.