Far-Infrared Therapy Induces the Nuclear Translocation of PLZF Which Inhibits VEGF-Induced Proliferation in Human Umbilical Vein Endothelial Cells

Many studies suggest that far-infrared (FIR) therapy can reduce the frequency of some vascular-related diseases. The non-thermal effect of FIR was recently found to play a role in the long-term protective effect on vascular function, but its molecular mechanism is still unknown. In the present study, we evaluated the biological effect of FIR on vascular endothelial growth factor (VEGF)-induced proliferation in human umbilical vein endothelial cells (HUVECs). We found that FIR ranging 3∼10 µm significantly inhibited VEGF-induced proliferation in HUVECs. According to intensity and time course analyses, the inhibitory effect of FIR peaked at an effective intensity of 0.13 mW/cm2 at 30 min. On the other hand, a thermal effect did not inhibit VEGF-induced proliferation in HUVECs. FIR exposure also inhibited the VEGF-induced phosphorylation of extracellular signal-regulated kinases in HUVECs. FIR exposure further induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO generation in VEGF-treated HUVECs. Both VEGF-induced NO and reactive oxygen species generation was involved in the inhibitory effect of FIR. Nitrotyrosine formation significantly increased in HUVECs treated with VEGF and FIR together. Inhibition of phosphoinositide 3-kinase (PI3K) by wortmannin abolished the FIR-induced phosphorylation of eNOS and Akt in HUVECs. FIR exposure upregulated the expression of PI3K p85 at the transcriptional level. We further found that FIR exposure induced the nuclear translocation of promyelocytic leukemia zinc finger protein (PLZF) in HUVECs. This induction was independent of a thermal effect. The small interfering RNA transfection of PLZF blocked FIR-increased PI3K levels and the inhibitory effect of FIR. These data suggest that FIR induces the nuclear translocation of PLZF which inhibits VEGF-induced proliferation in HUVECs

Sistematizaci?n de una metodolog?a para la evaluaci?n de sistemas de Producci?n en ecosistemas de manglar y su validaci?n en la bah?a de Punta Chame, Panam?

Tesis (M. Sc) -- CATIE, Turrialba (Costa Rica), 1995El presente trabajo tuvo como objetivo contribuir al desarrollo de una metodolog?a r?pida de evaluaci?n de los sistemas de Producci?n en ecosistemas de manglar, orientada a facilitar la toma de decisiones que conduzcan a la sostenibilidad. La misma se valid? en el manglar de la Bah?a de Chame, Panam?. Se analizaron y sistematizaron las experiencias del proyecto OLAFO en an?lisis de sistemas de Producci?n en zonas de frontera agr?cola, en las ?reas demostrativas de Nicaragua y Panam?. La metodolog?a propuesta se defini? bajo las caracter?sticas de que fuese de bajo costo, r?pida en su aplicaci?n y que permitiera un buen nivel de confiabilidad en la informaci?n. La metodolog?a parte del an?lisis y caracterizaci?n a nivel de la regi?n, comunidad, hasta llegar a la identificaci?n del(os) sistema(s) de Producci?n, bajo el concepto de la teor?a de sistemas. Se identificaron en cada uno de los niveles, componentes internos y externos flujos e interacciones, para conocer y entender los problemas, limitaciones y potencialidades presentes. En cada nivel se formulan objetivos y resultados esperados. Se llev? a cabo una evaluaci?n de la sostenibilidad en los ?mbitos ecol?gico, social y econ?mico basado en la informaci?n de las caracterizaciones. Se utilizaron variables e indicadores que fueran f?ciles de evaluar y donde la poblaci?n pudiera brindar informaci?n, para mantener la rapidez de la aplicaci?n metodol?gica. A las variables de tipo social y ecol?gico, se les asignaron valores de acuerdo a su importancia en el an?lisis, partiendo del supuesto de que no todas tienen el mismo peso en el an?lisis, siendo unas m?s importantes que otras. Se definieron niveles para cada variable (alto, medio, bajo) con sus respectivos criterios o indicadores y se determin? la sostenibilidad en cada caso, a trav?s de ?rboles de decisi?n. La validaci?n de la metodolog?a demostr? que la misma permite identificar el/los sistemas de Producci?n predominante y conocer el comportamiento de la estructura y funcionamiento del mismo, en un tiempo relativamente corto, sin mucho costo y con un buen nivel de informaci?n. A nivel de la regi?n se identificaron siete comunidades ligadas al manglar. De estas el poblado de Espav? presenta la mayor diversificaci?n de actividades, relacionadas a la extracci?n de varas, carb?n, astillas, pesca y conchas. Los sistemas de Producci?n identificados est?n representados por el grupo varas (11 por ciento), carb?n (22 por ciento), pesca (7 por ciento) asalariados (55 por ciento), y un grupo intermediarios de la comunidad (5 por ciento), calificados como comerciantes/patronos. La sostenibilidad ecol?gica del manglar se evalu? sostenible, a pesar de la calificaci?n baja de ciertas variables y elementos que hacen necesario un r?pido tratamiento, para mantener los atributos y usos del ecosistema. Socialmente la situaci?n es insostenible, con incipientes niveles de organizaci?n, autogesti?n comunitaria y pr?cticas de acumulaci?n. El estado de la sostenibilidad financiera, fue evaluado a trav?s del componente carb?n resultando sostenible, con indicadores financieros positivos. Las limitaciones en el an?lisis financiero, se dieron propiamente por el tiempo de la aplicaci?n metodol?gica, que no facilita conocer detalladamente los ingresos y costos monetarios y no monetarios del sistema, pero si la factibilidad de evaluar determinados componentes

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus

This study investigated the risk of non-melanoma skin cancer (NMSC) in pre-dialysis patients with chronic kidney disease (CKD) and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR) for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold), and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold). A higher SIR for NMSC was found in younger patients with CKD (age < 70 years, 1.34-fold; age 20–39 years, 1.63-fold), stage 5 CKD with anaemia (age < 70 years, 2.09-fold), and uraemic pruritus (age <70 years, 2.22-fold). Pre-dialysis patients with CKD are at higher risk of NMSC, especially those with advanced-stage CKD, and those with uraemic pruritus

Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1β, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia–reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1β, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI

Author Correction: Simvastatin reduces the carcinogenic effect of 3-methylcholanthrene in renal epithelial cells through histone deacetylase 1 inhibition and RhoA reactivation

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Effect of statins in preventing a 3MC-mediated decrease in cell-cycle regulatory proteins and in DNA incorporation induced by RhoA inactivation.

<p>Cells were pretreated with simvastatin or pravastatin for 1-cytosol and nuclear-cytosol of 3MC-treated MCVECs was analyzed to determine the action of statins in RhoA inactivation and their effect in preventing 3MC-mediated alterations in c-Raf/pRb2/HDAC1/histone deacetylation. (A) We analyzed fractionation after 1 h; thereafter, the levels of cell-cycle regulatory proteins were assessed by Western blot after 4 or 6 h of 3MC treatment. (B) Cells were transfected overnight with a plasmid containing DNRhoA, and 3MC treatment was administered for 6 h. A western blot analysis was conducted to examine the effect of DNRhoA on the cell-cycle regulatory proteins reduced by 3MC. GAPDH (or α-tubulin), Lamin A/C, and VE-cadherin were used as internal controls for the cytosol (or total), nuclear and membrane fractions, respectively, to verify equivalent loading. (C) Cells were pretreated with statins for 1 h; this was followed by the 3MC challenge, which was pulsed for 15 h with BrdU (Invitrogen; 0.75 μg/mL) incubation for the DNA incorporation assay. Fixed cells on coverslips were stained with a mouse anti-BrdU antibody conjugated with Texas Red. Red represents BrdU-positive staining. Identical fields were stained with DAPI (Invitrogen) to reveal the positions of cell nuclei. We recorded micrographs of the representative fields at 200× magnification (scale bar in white  = 250 μm). (D) Cell numbers were counted using a hemo-cytometer at the indicated time points in cells with various treatments. Data are presented as mean ± SEM of 3 independent experiments (*<i>P</i><0.05 vs. control group; ^#<i>P</i><0.05 vs. 3MC treatment alone).</p

Involvement of PTEN and PI3K in pRb2 hypophosphorylation induced by Ras/c-Raf inactivation.

<p>(A) Cells were pretreated with bpv (an inhibitor of PTEN) for 30 min or YS-49 (an activator of PI3K) for 1 h, followed by 1 h of 100 nM 3MC treatment. Total cell lysates, and extraction of nuclear and cytosolic proteins were analyzed using Western blot analysis for related signaling molecules involved in chromatin deaceylation. (B) Cells were transfected with a plasmid containing the DNRas gene to mimic the effect of 3MC. After 1 h of 3MC treatment, cells were harvested for Western blot analysis of the mentioned molecules in total and cytosolic-membrane extracts. GAPDH, Lamin A/C, and VE-cadherin were used as internal controls for the cytosol (or total), nuclear and membrane fractions, respectively, to verify equivalent loading. The lower panel shows the intensity of bands in the Western blots using densitometry. Data are presented as mean ± SEM of 3 independent experiments (*<i>P</i><0.05 vs. control group; ^#<i>P</i><0.05 vs. 3MC treatment alone).</p