RESUMEN
Rhizosphere is a soil volume of high spatio-temporal heterogeneity and intensive plant-soil-microbial interactions, for which visualization and process quantification is of highest scientific and applied relevance, but still very challenging. A novel methodology for quick assessment of two-dimensional distribution of available phosphorus (P) in rhizosphere was suggested, tested, and development up to the application platform. Available P was firstly trapped by an in-situ diffusive gradients in thin-films (DGT) sampler with precipitated zirconia as the binding gel, and subsequently, the loaded gel was analyzed with an optimized colorimetric imaging densitometry (CID). The imaging platform was established linking: i) DGT, ii) planar optode, and iii) soil zymography techniques to simultaneously determine available P, oxygen, and acid phosphatase in rhizosphere at sub-millimeter spatial scales. The DGT identified available P level in rice rhizosphere were spatially overlapping to the localized redox hotspots and phosphatase activity. The spatial relationship between available P and acid phosphatase activity was dependent on root development. The root radial oxygen loss (ROL) remained active during the experimental observations (2-3 days), while a flux of available P of 10 pg cm-2 s-1 was visualized within 2-3 mm of roots, confirming the correlative response of rice roots to oxygen secretion and P uptake. Summarizing, the established imaging platform is suitable to capture spatial heterogeneity and temporal dynamics of root activities, nutrient bioavailability, ROL and enzyme activities in rhizosphere.
Asunto(s)
Oryza , Fósforo , Fósforo/metabolismo , Rizosfera , Suelo , Oxígeno/metabolismo , Fosfatasa Ácida/metabolismo , Raíces de Plantas/metabolismoRESUMEN
The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, reduced mitochondrial fitness in TILs was induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signaling. Enforced accumulation of depolarized mitochondria with pharmacological inhibitors induced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation caused T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhanced T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal insights into how mitochondrial dynamics and quality orchestrate T cell antitumor responses and commitment to the exhaustion program.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Dinámicas Mitocondriales/inmunología , Biomarcadores , Epigénesis Genética , Epigenómica , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/inmunología , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Mitofagia , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Niacinamida/farmacología , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal , Estrés Fisiológico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides (BCPs) with trace amount contamination of LPS was treated with PB. 30 µg·mL-1 of PB, treating LPS (10 and 1 000 ng·mL-1 in stimulating RAW264.7 and MPMs respectively) at 37 °C for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB (30 µg·mL-1) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination (10 and 1 000 ng·mL-1).
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Polimixina B/análisis , Polisacáridos/farmacología , Animales , Bupleurum/química , Contaminación de Medicamentos , Medicamentos Herbarios Chinos/análisis , Lipopolisacáridos/análisis , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Polimixina B/farmacología , Polisacáridos/análisis , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To explore the characteristics of light propagation along the Pericardium Meridian and its surrounding areas at human wrist by using optical experiment and Monte Carlo method. METHODS: An experiment was carried out to obtain the distribution of diffuse light on Pericardium Meridian line and its surrounding areas at the wrist, and then a simplified model based on the anatomical structure was proposed to simulate the light transportation within the same area by using Monte Carlo method. RESULTS: The experimental results showed strong accordance with the Monte Carlo simulation that the light propagation along the Pericardium Meridian had an advantage over its surrounding areas at the wrist. CONCLUSION: The advantage of light transport along Pericardium Merdian line was related to components and structure of tissue, also the anatomical structure of the area that the Pericardium Meridian line runs.
Asunto(s)
Luz , Meridianos , Óptica y Fotónica , Pericardio , Muñeca , Difusión , Humanos , Modelos Teóricos , Método de Montecarlo , Óptica y Fotónica/métodos , Pericardio/fisiología , Muñeca/fisiologíaRESUMEN
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease leading to inflammatory tissue damage in multiple organs. The crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium have anticomplementary activity and immunomodulatory functions on macrophages. To study its potential benefit on SLE, we examined effects of BPs on MRL-lpr mice, which have similar disease features to human SLE. MRL-lpr mice were treated orally with BPs 15, 30, or 60 mg kg⻹ day⻹ for 12 weeks and their SLE characteristics were evaluated. The results revealed that BPs elongated life span, improved kidney function, delayed lymphadenopathy, and reduced autoantibodies. It seemed to be mediated by inhibition of complement and macrophages activation and suppression of interferon-γ (IFN-γ) and interleukin-6 (IL-6) gene expression in the kidney. These results implicate that BPs may be an immunomodulator for the treatment of autoimmune diseases like SLE.