RESUMEN
Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP's pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management.
Asunto(s)
Productos Biológicos , Retinopatía de la Prematuridad , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/terapia , Retinopatía de la Prematuridad/metabolismo , Humanos , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Recién Nacido , Animales , Recien Nacido PrematuroRESUMEN
High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/ß-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.
Asunto(s)
Antiinfecciosos Locales , Carbamatos , Cumarinas , Proteína HMGB1 , Sepsis , Animales , Humanos , Ratones , Antiinfecciosos Locales/farmacología , Antiinfecciosos Locales/uso terapéutico , Modelos Animales de Enfermedad , Proteína HMGB1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Sepsis/metabolismoRESUMEN
Exosomes are extracellular vesicles that can contain DNA, RNA, proteins, and metabolites. They are secreted by cells and play a regulatory role in various biological responses by mediating cell-to-cell communication. Moreover, exosomes are of interest in developing therapies for retinal vascular disorders because they can deliver various substances to cellular targets. According to recent research, exosomes can be used as a strategy for managing retinal vascular diseases, and they are being investigated for therapeutic purposes in eye conditions, including glaucoma, dry eye syndrome, retinal ischemia, diabetic retinopathy, and age-related macular degeneration. However, the role of exosomal noncoding RNA in retinal vascular diseases is not fully understood. Here, we reviewed the latest research on the biological role of exosomal noncoding RNA in treating retinal vascular diseases. Research has shown that noncoding RNAs, including microRNAs, circular RNAs, and long noncoding RNAs play a significant role in the regulation of retinal vascular diseases. Furthermore, through exosome engineering, the expression of relevant noncoding RNAs in exosomes can be controlled to regulate retinal vascular diseases. Therefore, this review suggests that exosomal noncoding RNA could be considered as a biomarker for diagnosis and as a therapeutic target for treating retinal vascular disease.
RESUMEN
Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.
Asunto(s)
Panax , Sarcopenia , Animales , Ratones , Humanos , Sarcopenia/tratamiento farmacológico , Sarcopenia/metabolismo , Frutas , Polvos/metabolismo , Polvos/farmacología , Atrofia Muscular/tratamiento farmacológico , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismoRESUMEN
Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration.
Asunto(s)
Sarcopenia , Ratones , Animales , Sarcopenia/metabolismo , Calidad de Vida , Línea Celular , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas , Desarrollo de MúsculosRESUMEN
Immobilization of radioactive borate waste (RBW) using a geopolymer with a high Si/Al ratio has been challenging because boron-silicon networks lower the compressive strength and delay the setting time. In this study, metakaolin-based geopolymer waste form to immobilize simulant RBW was fabricated using different Si/Al ratios (1.0-1.4) and curing temperatures (26 and 60 â). The 7-day compressive strength results revealed that a certain amount of silicon and an elevated curing temperature are required to achieve high compressive strength and waste loading. Following waste acceptance criteria tests, all geopolymers exhibited compressive strengths higher than 3.445 MPa. The leachability index of boron was higher than 6.0, and the leaching mechanism was identified as diffusion. No significant structural changes in the geopolymer were observed after thermal cycling and gamma irradiation tests. The physically bound or unincorporated RBW was leached out of the geopolymer during water immersion and leaching tests; however, boron, which was chemically connected with silicon, was present as an inert phase together with a geopolymer binder. Consequently, immobilizing RBW using a geopolymer with a low Si/Al ratio (1.4) is beneficial in terms of RBW loading and structural durability.
RESUMEN
BACKGROUND: Patients with cancer undergoing chemotherapy experience cachexia with anorexia, body weight loss, and the depletion of skeletal muscles and adipose tissues. Effective treatment strategies for chemotherapy-induced cachexia are scarce. The growth differentiation factor 15 (GDF15)/GDNF family receptor alpha-like (GFRAL)/rearranged during transfection (RET) axis is a critical signalling pathway in chemotherapy-induced cachexia. In this study, we developed a fully human GFRAL antagonist antibody and investigated whether it inhibits the GDF15/GFRAL/RET axis, thereby alleviating chemotherapy-induced cachexia in tumour-bearing mice. METHODS: Anti-GFRAL antibodies were selected via biopanning, using a human combinatorial antibody phage library. The potent GFRAL antagonist antibody A11 was selected via a reporter cell assay and its inhibitory activity of GDF15-induced signalling was evaluated using western blotting. To investigate the in vivo function of A11, a tumour-bearing mouse model was established by inoculating 8-week-old male C57BL/6 mice with B16F10 cells (n = 10-16 mice per group). A11 was administered subcutaneously (10 mg/kg) 1 day before intraperitoneal treatment with cisplatin (10 mg/kg). Animals were assessed for changes in food intake, body weight, and tumour volume. Plasma and key metabolic tissues such as skeletal muscles and adipose tissues were collected for protein and mRNA expression analysis. RESULTS: A11 reduced serum response element-luciferase reporter activity up to 74% (P < 0.005) in a dose-dependent manner and blocked RET phosphorylation up to 87% (P = 0.0593), AKT phosphorylation up to 28% (P = 0.0593) and extracellular signal regulatory kinase phosphorylation up to 75% (P = 0.0636). A11 inhibited the action of cisplatin-induced GDF15 on the brainstem and decreased GFRAL-positive neuron population expressing c-Fos in the area postrema and nucleus of the solitary tract by 62% in vivo (P < 0.05). In a melanoma mouse model treated with cisplatin, A11 recovered anorexia by 21% (P < 0.05) and tumour-free body weight loss by 13% (P < 0.05). A11 significantly improved the cisplatin-induced loss of skeletal muscles (quadriceps: 21%, gastrocnemius: 9%, soleus: 13%, P < 0.05) and adipose tissues (epididymal white adipose tissue: 37%, inguinal white adipose tissue: 51%, P < 0.05). CONCLUSIONS: Our study suggests that GFRAL antagonist antibody may alleviate chemotherapy-induced cachexia, providing a novel therapeutic approach for patients with cancer experiencing chemotherapy-induced cachexia.
Asunto(s)
Antineoplásicos , Melanoma , Ratones , Humanos , Masculino , Animales , Caquexia/inducido químicamente , Caquexia/tratamiento farmacológico , Factor Neurotrófico Derivado de la Línea Celular Glial , Anorexia/metabolismo , Cisplatino , Ratones Endogámicos C57BL , Antineoplásicos/efectos adversosRESUMEN
A small natural substance called cirsilineol (CSL), which was discovered in the plant Artemisia vestita, is lethal to many cancer cells and has antioxidant, anticancer, and antibacterial properties. Here, we investigated the underlying mechanisms of the antithrombotic action of CSL. We demonstrated that CSL has antithrombotic efficacy comparable to rivaroxaban, a direct blood coagulation factor Xa (FXa) inhibitor employed as a positive control, in inhibiting the enzymatic activity of FXa and the platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a thromboxane A2 analog. The expression of P-selectin, the phosphorylation of myristoylated alanine-rich C kinase substrate by U46619 or ADP, and the activation of PAC-1 in platelets were inhibited by CSL. Nitric oxide production was increased by CSL in ADP- or U46619-treated human umbilical vein endothelial cells (HUVECs), although excessive endothelin-1 secretion was suppressed. CSL demonstrated strong anticoagulant and antithrombotic effects in a mouse model of arterial and pulmonary thrombosis. Our findings suggest that CSL is a potential pharmacological candidate for a novel class of anti-FXa and antiplatelet medications.
RESUMEN
The skin aging process is governed by intrinsic and extrinsic factors causing skin wrinkles, sagging, and loosening. The 1-monoeicosapentaenoin (1-MEST) is a component isolated from Micractinium, a genus of microalgae (Chlorophyta, Trebouxiophyceae). However, the anti-wrinkle effects of 1-MEST are not yet known. This study aimed to evaluate the anti-wrinkle effects of 1-MEST in vitro and in clinical trials. The cytotoxicity of 1-MEST was investigated in vitro using the MTS assay in human epidermal keratinocytes (HEKs). Expression of matrix metalloproteinase (MMP)-1 and MMP-9 was determined by ELISA in HEKs irradiated with UVB after treatment with 1-MEST. A split-face randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of 1-MEST. The study evaluated wrinkle parameters and visual assessment, self-efficacy and usability questionnaires, and adverse events. The study showed that the 1-MEST was not cytotoxic in HEKs, suppressed MMP-1 secretion and MMP-9 protein expression in HEKs irradiated with UVB. The wrinkle parameters and mean visual assessment score were significantly decreased in the test group after 12 weeks and differed from the control group. There were no significant differences in efficacy and usability. Adverse effects were also not observed. The 1-MEST showed anti-wrinkle properties to slow down or prevent skin aging.
RESUMEN
Extracellular vesicles (EVs) mediate cell-cell crosstalk by carrying bioactive molecules derived from cells. Recently, immune cell-derived EVs have been reported to regulate key biological functions such as tumor progression. CD4+ T cells orchestrate overall immunity; however, the biological role of their EVs is unclear. This study reveals that EVs derived from CD4+ T cells increase the antitumor response of CD8+ T cells by enhancing their proliferation and activity without affecting regulatory T cells (Tregs). Moreover, EVs derived from interleukin-2 (IL2)-stimulated CD4+ T cells induce a more enhanced antitumor response of CD8+ T cells compared with that of IL2-unstimulated CD4+ T cell-derived EVs. Mechanistically, miR-25-3p, miR-155-5p, miR-215-5p, and miR-375 within CD4+ T cell-derived EVs are responsible for the induction of CD8+ T cell-mediated antitumor responses. In a melanoma mouse model, the EVs potently suppress tumor growth through CD8+ T cell activation. This study demonstrates that the EVs, in addition to IL2, are important mediators between CD4+ and CD8+ T cells. Furthermore, unlike IL2, clinically used as an antitumor agent, CD4+ T cell-derived EVs stimulate CD8+ T cells without activating Tregs. Therefore, CD4+ T cell-derived EVs may provide a novel direction for cancer immunotherapy by inducing a CD8+ T cell-mediated antitumor response.
Asunto(s)
Vesículas Extracelulares , MicroARNs , Animales , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Interleucina-2 , Ratones , Linfocitos T ReguladoresRESUMEN
Fifteen airborne particulate matter-bound metals were analyzed at 14 sites in four large cities (Seoul, Incheon, Busan, Daegu) in South Korea, between August 2013 and June 2017. Among the seven sources resolved by positive matrix factorization, soil dust and marine aerosol accounted for the largest and second largest portions in the three cities; however, in Seoul, soil dust and traffic occupied the largest and the second largest, respectively. Non-carcinogenic risk assessed by inhalation of eight metals (Cd, Co, Ni, Pb, As, Al, Mn, and V) was greater than the hazard index (HI) of 1 at four sites located at or near the industrial complexes. Cumulative incremental lifetime cancer risk (ILCR) due to exposure to five metals (Cd, Co, Ni, Pb, and As) exceeded the 10-6 cancer benchmark at 14 sites and 10-5 at six sites, which includes four sites with HI greater than 1. The largest contributor to ILCR was coal combustion in Seoul, Incheon, and Daegu, and industry sources in Busan. Moreover, industry sources were the largest contributors to non-carcinogenic risk in Seoul, Busan, and Daegu, and soil dust was in Incheon. Incheon had the highest HI in spring because of the higher contribution of soil dust sources than in other seasons. The higher ILCR in Incheon in spring and winter and higher ILCR and HI in Daegu in autumn were mainly due to the influence of industry or coal combustion sources. Statistically significant differences in the ILCR and HI values among the sampling sites in Busan and Daegu resulted from the higher contribution of industry sources at a certain site in the respective city.
Asunto(s)
Contaminantes Atmosféricos , Metales Pesados , Neoplasias , Contaminantes Atmosféricos/análisis , Cadmio , China , Ciudades , Carbón Mineral , Polvo/análisis , Monitoreo del Ambiente/métodos , Humanos , Plomo , Metales Pesados/análisis , Material Particulado/análisis , República de Corea , Medición de Riesgo , Estaciones del Año , SueloRESUMEN
CXC chemokine receptor 7 (CXCR7) is frequently overexpressed in cancer and plays a significant role in tumor growth and metastasis. Consequently, inhibition of CXCR7 is important for treatment strategies. However, little is known concerning the biological role of CXCR7 and its underlying mechanisms in head and neck squamous cell carcinoma (HNSCC). The present study investigated the role of CXCR7 in HNSCC, as well as the effects of decursin, a pyranocoumarin compound isolated from Angelica gigas Nakai, on CXCR7 and its downstream signaling. Expression levels of CXCR7 in HNSCC cells were examined using flow cytometry, reverse transcriptase PCR, western blot analysis, and immunofluorescence. The effects of CXCR7 on cell proliferation, migration, and invasion were studied using CCK8, gap closure, and transwell assays. The results revealed that decursin significantly reduced CXCR7 expression and inhibited cell proliferation, migration, and invasion of human HNSCC cell lines. In addition, decursin induced G0/G1 cell cycle arrest in CXCR7overexpressing cells and decreased the levels of cyclin A, cyclin E, and CDK2. Furthermore, CXCR7 promoted cancer progression via the STAT3/cMyc pathway in HNSCC; suppression of CXCR7 with decursin prevented this effect. These results suggest that CXCR7 promotes cancer progression through the STAT3/cMyc pathway and that the natural compound decursin targets CXCR7 and may be valuable in the treatment of HNSCC.
Asunto(s)
Benzopiranos/farmacología , Butiratos/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Receptores CXCR/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Regulación hacia Abajo , Activadores de Enzimas/farmacología , HumanosRESUMEN
Sulfate radical advance oxidation processes (SR-AOPs) have attracted a greater attention as a suitable alternative of the hydroxyl radical based advance oxidation process (HR-AOPs). In this study, for the first time we report liquid phase mineralization of nuclear grade cationic IRN-77 resin in Co2+/peroxymonosulfate (PMS) based SR-AOPs. After the dissolution of cationic IRN-77 resin, 30 volatile and 15 semi-volatile organic compounds were analyzed/detected using non-targeted GC-MS analysis. The optimal reaction parameters for the highest chemical oxygen demand (COD) removal (%) of IRN-77 resin were determined, and the initial pH, PMS dosage, and reaction temperature were found to be the most influential parameters for the resin degradation. We successfully achieved â¼90% COD removal (1000 mg/L; 1000 ppm) of dissolved spent resin for SR-AOPs by optimizing the reaction parameters as initial pH = 9, Co2+ = 4 mM (catalyst), PMS = 60 mM (as oxidant) at 60 °C temperature for 60 min reaction. The electron spin resonance spectroscopy (ESR) spectra confirmed the presence of SO4â- and OHâ as main reactive species in the Co2+/PMS resin system. In addition, Fourier transform infrared spectroscopy (FT-IR) analyses were used for structural characterization of solid and liquid phase resin samples. We believe that this work will offer a robust approach for the effective treatment of spent resin generated from nuclear industry.
Asunto(s)
Resinas de Intercambio Iónico , Peróxidos , Oxidación-Reducción , Espectroscopía Infrarroja por Transformada de Fourier , SulfatosRESUMEN
The cardiotoxicity of various anticancer therapies, including radiotherapy, can lead to cardiovascular complications. These complications can range from damaging cardiac tissues within the irradiation field to increasing the long-term risks of developing heart failure, coronary artery disease, and myocardial infarction. We analyzed radiation-induced metabolites capable of mediating critical biological processes, such as inflammation, senescence, and apoptosis. Previously, by applying QTOF-MASS analysis to irradiated human fibroblasts, we identified that metabolite sets of lysophosphatidylcholine (LPC) were increased in these cells. In this study, radiation-induced LPC accumulation in human aortic endothelial cells (HAECs) increased reactive oxygen species (ROS) production and senescence-associated-beta-galactosidase staining, in addition to decreasing their tube-forming ability. Knockdown of lipoprotein-associated phospholipase A2 (Lp-PLA2) with small interfering RNA (siRNA) inhibited the increased LPC production induced by radiation, and reduced the radiation-induced cell damage produced by ROS and oxidized low-density lipoprotein (LDL). Lp-PLA2 depletion abolished the induction of proinflammatory factors, such as interleukin 1ß, tumor necrosis factor-alpha, matrix metalloproteinase 2, and matrix metalloproteinase 9, as well as adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and E-selection. Likewise, we showed that Lp-PLA2 expression was upregulated in the vasculature of irradiated rat, resulting in increased LPC production and LDL oxidation. Our data demonstrate that radiation-induced LPC production is a potential risk factor for cardiotoxicity that is mediated by Lp-PLA2 activity, suggesting that LPC and Lp-PLA2 offer potential diagnostic and therapeutic approaches to cardiovascular damage during radiotherapy.
Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterasa/efectos de la radiación , Células Endoteliales/patología , Células Endoteliales/efectos de la radiación , Lisofosfatidilcolinas/metabolismo , Fosfolipasas A2/metabolismo , Fosfolipasas A2/efectos de la radiación , Animales , Aorta/patología , Aorta/efectos de la radiación , Citocinas/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Inflamación/metabolismo , Microtúbulos/efectos de los fármacos , Microtúbulos/efectos de la radiación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/efectos de la radiación , Radiación Ionizante , Ratas , Ratas Endogámicas F344 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Leaching behaviors and mechanisms of commercialized glass wasteforms to sequester low-level solid-wastes were investigated: SG glass for resin waste and DG-2 glass for dry active waste. After ANS 16.1 leaching test, leachabilities of the nuclides, Co, Cs, and Sr, were all lager than 14, which met the requirement of the US-Nuclear Regulatory Commission. Holes of diameters 5-10⯵m remained on the surface of the SG and crevices of lengths 10-50⯵m were observed on the surface of the DG-2. We analyzed elemental compositions of the SG and the DG-2 with depths. For the SG, Si, Al, Ca, and Mg were accumulated and Na was depleted up to nearly 1.5⯵m compared to an internal glass. For the DG-2, concentrations of B, Na, Al, Ca and Sr started to decrease from 2.5⯵m even though other minor elements are still remained their concentrations. We suggested leaching mechanisms: alkali elements including H would diffuse through the holes on the SG, while most of the elements including Si and Al would diffuse through the crevices on the DG-2.
RESUMEN
Stromal cell-derived factor 1 (SDF-1) and its main receptor, CXC chemokine receptor 4 (CXCR4), play a critical role in endothelial cell function regulation during cardiogenesis, angiogenesis, and reendothelialization after injury. The expression of CXCR4 and SDF-1 in brain endothelial cells decreases due to ionizing radiation treatment and aging. SDF-1 protein treatment in the senescent and radiation-damaged cells reduced several senescence phenotypes, such as decreased cell proliferation, upregulated p53 and p21 expression, and increased senescence-associated beta-galactosidase (SA-ß-gal) activity, through CXCR4-dependent signaling. By inhibiting extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription protein 3 (STAT3), we confirmed that activation of both is important in recovery by SDF-1-related mechanisms. A CXCR4 agonist, ATI2341, protected brain endothelial cells from radiation-induced damage. In irradiation-damaged tissue, ATI2341 treatment inhibited cell death in the villi of the small intestine and decreased SA-ß-gal activity in arterial tissue. An ischemic injury experiment revealed no decrease in blood flow by irradiation in ATI2341-administrated mice. ATI2341 treatment specifically affected CXCR4 action in mouse brain vessels and partially restored normal cognitive ability in irradiated mice. These results demonstrate that SDF-1 and ATI2341 may offer potential therapeutic approaches to recover tissues damaged during chemotherapy or radiotherapy, particularly by protecting vascular endothelial cells.
Asunto(s)
Vasos Sanguíneos/citología , Encéfalo/irrigación sanguínea , Quimiocina CXCL12/metabolismo , Irradiación Craneana/efectos adversos , Receptores CXCR4/metabolismo , Animales , Vasos Sanguíneos/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Línea Celular , Senescencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de la radiación , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Lipopéptidos/administración & dosificación , Lipopéptidos/farmacología , Ratones , Transducción de Señal/efectos de la radiaciónRESUMEN
The first 3-D direct observation of clusters of Nd oxide inside silicate glasses was achieved using atom probe tomography. Three-dimensional elemental maps of major chemical elements in glasses such as Si, Al, Zn and O showed no evidence of regions that had concentrations higher than the average values, whereas the Nd aggregated into regions of high concentration. Elemental maps of Nd and Pb recorded from the glasses containing PbS QDs showed highly-concentrated areas of both elements at the same locations; this result indicates that PbS QDs formation started in association with the Nd clusters.
RESUMEN
Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) is a potent transcription factor for mitochondrial function, lipid metabolism, and detoxification in a variety of tissues. PGC1α also promotes brain cell proliferation and memory. However, how PGC1α is involved in aging is not well known. In brain endothelial cells, we found that PGC1α knockdown accelerated DNA damage-induced senescence, evidenced by an increase in senescence-associated ß-galactosidase-positive cells and a decrease in cell proliferation and adenosine triphosphate production. PGC1α knockdown delayed DNA damage repair mechanisms compared with the wild-type condition as shown by γ-H2AX foci staining assay. Overexpression of PGC1α reduced senescence-associated ß-galactosidase-positive cells and increased the proliferation of senescent cells. Although PGC1α protein levels were not decreased, PGC1 acetylation was increased by ionizing radiation treatment and aging. Histone deacetylase 1 (HDAC1) expression was decreased by ionizing radiation treatment and aging, and downregulation of HDAC1 induced acetylation of PGC1α. HDAC1 knockdown affected sirtuin 1 expression and decreased its deacetylation of PGC1α. In the mouse brain cortex, acetylation of PGC1α was increased by ionizing radiation treatment. These results suggest that acetylation of PGC1α is induced by DNA damage agents such as ionizing radiation, which deregulates mitochondrial mechanisms and metabolism, resulting in acceleration of radiation-induced senescence. Therefore, acetylation of PGC1α may be a cause of brain disorders and has the potential to serve as a therapeutic target for radiation-induced senescence after radiation cancer therapy.
Asunto(s)
Senescencia Celular/efectos de la radiación , Regulación hacia Abajo , Histona Desacetilasa 1/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Acetilación , Animales , Encéfalo/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de la radiación , Proliferación Celular , Células Cultivadas , Senescencia Celular/fisiología , Complejo IV de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/efectos de la radiación , Células Endoteliales/patología , Células Endoteliales/efectos de la radiación , Fibronectinas/metabolismo , Fibronectinas/efectos de la radiación , Expresión Génica , Humanos , Ratones Endogámicos C57BL , ATPasas de Translocación de Protón Mitocondriales/metabolismo , ATPasas de Translocación de Protón Mitocondriales/efectos de la radiación , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/efectos de la radiación , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , ARN Mensajero/metabolismo , Exposición a la Radiación/efectos adversosRESUMEN
Calcium-aluminoborate (CAB) glasses were developed to sequester new waste compositions made of several rare-earth oxides generated from the pyrochemical reprocessing of spent nuclear fuel. Several important wasteform properties such as waste loading, processability and chemical durability were evaluated. The maximum waste loading of the CAB compositions was determined to be ~56.8 wt%. Viscosity and the electrical conductivity of the CAB melt at 1300 °C were 7.817 Pa·s and 0.4603 S/cm, respectively, which satisfies the conditions for commercial cold-crucible induction melting (CCIM) process. Addition of rare-earth oxides to CAB glasses resulted in dramatic decreases in the elemental releases of B and Ca in aqueous dissolution experiments. Normalized elemental releases from product consistency standard chemical durability test were <3.62·10-5 g·m-2 for Nd, 0.009 g·m-2 for Al, 0.067 g·m-2 for B and 0.073 g·m-2 for Ca (at 90, after 7 days, for SA/V = 2000m-1); all meet European and US regulation limits. After 20 d of dissolution, a hydrated alteration layer of ~ 200-nm-thick, Ca-depleted and Nd-rich, was formed at the surface of CAB glasses with 20 mol% Nd2O3 whereas boehmite [AlO(OH)] secondary crystalline phases were formed in pure CAB glass that contained no Nd2O3.
RESUMEN
A phosphor-in-glass (PiG) with red and green phosphors using Nd-doped glass as a host matrix was fabricated to produce a white light emitting diode (wLED) with a wide color gamut. The Lu3Al5O12:Ce3+ and CaAlSiN3:Eu2+ contents were adjusted to achieve white emission for liquid crystal display (LCD) applications. The silicate glass was doped with varying concentrations of Nd2O3 to modify the photoluminescence spectra of the wLED, by the hypersensitive absorption of the Nd3+:I9/24âG5/24,G27/2 transition. The color coordination, the color rendering index, and the color co-related temperature of the PiG-mounted LEDs were modified by the introduction of Nd3+. The color gamut of the wLED was monitored and found to have effectively improved with the Nd3+-doped silicate glass.