Beyond the Antioxidant Activity of Dietary Polyphenols in Cancer: the Modulation of Estrogen Receptors (ERs) Signaling.

The potential "health benefits" of dietary polyphenols have been ascribed to their direct antioxidant activity and their impact on the regulation of cell and tissue redox balance. However, because of the relative poor bioavailability of many of these compounds, their effects could not be easily explained by the antioxidant action, which may occur only at high circulating and tissue concentrations. Therefore, many efforts have been put forward to clarify the molecular mechanisms underlining the biological effect of polyphenols in physiological and pathological conditions. Polyphenols' bioavailability, metabolism, and their effects on enzyme, membrane, and/or nuclear receptors and intracellular transduction mechanisms may define the overall impact of these compounds on cancer risk and progression, which is still debated and not yet clarified. Polyphenols are able to bind to estrogen receptor α (ERα) and ß (ERß), and therefore induce biological effects in human cells through mimicking or inhibiting the action of endogenous estrogens, even at low concentrations. In this work, the role and effects of food-contained polyphenols in hormone-related cancers will be reviewed, mainly focusing on the different polyphenols' mechanisms of action with particular attention on their estrogen receptor-based effects, and on the consequences of such processes on tumor progression and development.

Análisis de la eficacia de la doble broncodilatación (LABA+LAMA) en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) y cáncer de pulmón / Efficacy of double bronchodilation (LABA+LAMA) in patients with chronic obstructive pulmonary disease (COPD) and lung cancer

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Upregulation of rat liver PPARα-FGF21 signaling by a docosahexaenoic acid and thyroid hormone combined protocol.

Prevention of ischemia-reperfusion liver injury is achieved by a combined omega-3 and thyroid hormone (T3 ) protocol, which may involve peroxisome-proliferator activated receptor-α (PPAR-α)-fibroblast growth factor 21 (FGF21) signaling supporting energy requirements. Combined docosahexaenoic acid (DHA; daily doses of 300 mg/kg for 3 days) plus 0.05 mg T3 /kg given to fed rats elicited higher hepatic DHA contents and serum T3 levels, increased PPAR-α mRNA and its DNA binding, with higher mRNA expression of the PPAR-α target genes for carnitine-palmitoyl transferase 1α, acyl-CoA oxidase, and 3-hydroxyl-3-methylglutaryl-CoA synthase 2, effects that were mimicked by 0.1 mg T3 /kg given alone or by the PPAR-α agonist WY-14632. Under these conditions, the mRNA expression of retinoic X receptor-α (RXR-α) is also increased, with concomitant elevation of the hepatic mRNA and protein FGF21 levels and those of serum FGF21. It is concluded that PPAR-α-FGF21 induction by DHA combined with T3 may involve ligand activation of PPAR-α by DHA and enhanced expression of PPAR-α by T3 , with consequent upregulation of the FGF21 that is controlled by PPAR-α. Considering the beneficial effects of PPAR-α-FGF21 signaling on carbohydrate and lipid metabolism, further investigations are required to clarify its potential therapeutic applications in human metabolic disorders. © 2016 BioFactors, 42(6):638-646, 2016.

Cambios en el estadio y presentación clínica del cáncer de pulmón a lo largo de dos décadas / Changes in Clinical Presentation and Staging of Lung Cancer over Two Decades

INTRODUCCIÓN: En la pasada década observamos que en nuestra área sanitaria se produjeron importantes cambios clínico-epidemiológicos en el cáncer de pulmón (CP) con respecto a la década anterior. En los últimos 10 años se han puesto en marcha circuitos asistenciales específicos de CP y se ha intensificado la búsqueda activa de casos. El presente estudio fue realizado para analizar la evolución de dichos cambios 20 años después. METODOLOGÍA: Estudio retrospectivo en el que se comparan aspectos clínico-epidemiológicos de 2 series históricas de pacientes con CP (periodo 1992-1994 [serie 1, 164 pacientes] y periodo 2004-2006 [serie 2, 250 pacientes]) con una serie actual correspondiente al periodo 2011-2012 (serie 3, 209 pacientes). RESULTADOS: Se incluyeron 209 pacientes del periodo 2011-2012 (serie 3). Al comparar las series 3 y 2 se observa un aumento no significativo de la frecuencia de tabaquismo en la mujer (59% vs 41%, p = 0,25) y se mantiene la frecuencia de adenocarcinoma (45% vs 44% p = 0,9). Los principales cambios observados fueron el incremento de casos con neoplasias previas (23% vs 16%, p = 0,04), de pacientes sin clínica relacionada de CP (33% vs 16%, p < 0,001) y los diagnósticos de CPNM (CP no microcítico) en estadios localizados (42% vs 24% en serie 2, p < 0,001 y 14% en serie 1, p < 0,001). CONCLUSIONES: Se ha incrementado significativamente el número de pacientes diagnosticados en estadios localizados. También han aumentado los pacientes sin clínica relacionada con CP y con el antecedente de cáncer previo

INTRODUCTION: Important clinical and epidemiological changes have been observed in lung cancer (LC) in our healthcare area compared to the previous decade. In the last 10 years, specific LC care circuits have been implemented and the active search for cases has been stepped up. The aim of this study was to analyze the progress of these changes over the last 20 years. METHODS: This is a retrospective study comparing clinical and epidemiological changes between 2 historical cohorts of LC patients (1992-1994 [group 1, 164 patients] and 2004-2006 [group 2, 250 patients]) and a current group from the period 2011-2012 (group 3, 209 patients). RESULTS: Two hundred and nine (209) LC patients were included in group 3 (2011-2012 period). After comparing groups 3 and 2, a non-significant rise in smoking was observed in women (59% vs 41%, P = 0.25), while the prevalence of adenocarcinoma was unchanged (45% vs 44%, P = 0.9). The main changes observed were the increase in cases with previous malignancies (23% vs 16%, P = 0.04), the rise in patients with no associated LC symptoms (33% vs 16%, P < 0.001), and an increased number of localized NSCLC (non-small cell LC) diagnoses (42% vs 24% in series 2, P < 0.001 and 14.2% in series 1, P < 0.001). CONCLUSIONS: The number of LC patients diagnosed in localized stages has increased significantly. Furthermore, the number of patients with no symptoms associated with LC and with a history of previous malignancy was significantly increased

Diseño y validación de las escalas de evaluación del impacto psicológico de sucesos vitales pasados: el papel del pensamiento rumiativo y el crecimiento personal / Design and validation of the scales for the assessment of the psychological impact of past life events: the role of ruminative thought and personal growth

Introducción. El malestar emocional de las personas mayores se relaciona frecuentemente con procesos de rumiación acerca de episodios vitales acaecidos a lo largo de su vida. El tipo de afrontamiento desplegado ante tales episodios podría contribuir a explicar el bienestar emocional actual de las personas mayores: pueden percibir que han crecido personalmente tras el episodio y/o pueden presentar pensamientos rumiativos sobre tales episodios, que generan malestar emocional. Este trabajo describe el desarrollo y análisis de las propiedades psicométricas de las escalas de evaluación del impacto psicológico de sucesos vitales pasados (EEIPSV): la escala de ocurrencia de sucesos vitales (EO), la escala de pensamiento rumiativo (EPR) y la escala de crecimiento personal (ECP). Material y métodos. Participaron 393 personas mayores no institucionalizadas, residentes en la comunidad de Madrid (edad media: 71,5 años; DE: 6,9). Además de las EEIPSV, se evaluaron las variables: sintomatología depresiva, ansiedad, bienestar psicológico, satisfacción con la vida, función física y vitalidad. Resultados. Los resultados del análisis interjueces sugieren la existencia de 2 factores en la EO: sucesos positivos y negativos. Los análisis factoriales confirmatorios respaldan esta estructura bidimensional tanto para la escala EPR como la ECP. Se obtuvieron buenos índices de consistencia interna para cada escala y subescala, así como buenos índices de validez de criterio y convergente. Conclusiones. Tanto el pensamiento rumiativo sobre sucesos vitales pasados como el crecimiento personal se relacionan con el bienestar emocional de las personas mayores. Las EEIPSV presentan buenas propiedades psicométricas que justifican su uso con población mayor(AU)

Introduction. Older people's emotional distress is often related to rumination processes focused on past vital events occurred during their lives. The specific coping strategies displayed to face those events may contribute to explain older adults’ current well-being: they can perceive that they have obtained personal growth after those events and/or they can show a tendency to have intrusive thoughts about those events. This paper describes the development and analysis of the psychometric properties of the Scales for the Assessment of the Psychological Impact of Past Life Events (SAPIPLE): the past life events-occurrence scale (LE-O), ruminative thought scale (LE-R) and personal growth scale (LE-PG). Material and methods. Participants were 393 community dwelling elderly (mean age=71.5 years old; SD=6.9). In addition to the SAPIPLE scales, depressive symptomatology, anxiety, psychological well-being, life satisfaction, physical function and vitality have been assessed. Results. The inter-rater agreement's analysis suggests the presence of two factors in the LE-O: positive and negative vital events. Confirmatory Factor Analysis (CFA) supported this two-dimensional structure for both the LE-R and the LE-PG. Good internal consistency indexes have been obtained for each scale and subscale, as well as good criterion and concurrent validity indexes. Conclusions. Both ruminative thoughts about past life events and personal growth following those events are related to older adults’ current well-being. The SAPIPLE presents good psychometric properties that justify its use for elderly people(AU)

Short- and long-term effectiveness of a supervised training program in spirometry use for primary care professionals.

INTRODUCTION: Despite the importance of spirometry, its use and quality are limited in the Primary Care setting. There are few accredited training programs that have demonstrated improvement in the quality of spirometric studies. In this paper, we analyze the short- and long-term effectiveness of a supervised training program for performing and interpreting spirometries. METHODOLOGY: Ours is an intervention study with before and after measurements. The target population included teams of physicians and nursing staff at 26 health-care centers in the area of Vigo (Galicia, Spain). The structured training program involved 2 theoretical and practical training sessions (that were 2months apart), an intermediate period of 30 supervised spirometries performed in the respective centers and weekly e-mail exercises. Effectiveness was evaluated using exercises at the beginning (test 1) and the end (test 2) of the 1st day, 2nd day (test 3) and one year later (test 4), as well as the analysis of spirometries done in month1, month2 and one year later. Participants also completed a survey about their satisfaction. RESULTS: 74 participants initiated the program; 72 completed the program, but only 45 participated in the one-year evaluation. Mean test scores were: 4.1±1.9 on test 1; 7.5±1.6 on test 2; 8.9±1.3 on test 3, and 8.8±1.4 on test 4. During month1, the percentage of correctly done/interpreted tests was 71%, in month two it was 91% and after one year it was 83% (P<.05). CONCLUSIONS: A training program based on theoretical and practical workshops and a supervised follow-up of spirometries significantly improved the ability of Primary Care professionals to carry out and interpret spirometric testing, although the quality of the tests diminished over time.

N-3 long-chain polyunsaturated fatty acid supplementation significantly reduces liver oxidative stress in high fat induced steatosis.

Omega-3 (n-3) long-chain polyunsaturated fatty acids (n-3 LCPUFA) are associated with several physiological functions, suggesting that their administration may prevent non transmissible chronic diseases. Therefore, we investigate whether dietary n-3 LCPUFA supplementation triggers an antioxidant response preventing liver steatosis in mice fed a high fat diet (HFD) in relation to n-3 LCPUFA levels. Male C57BL/6J mice received (a) control diet (10% fat, 20% protein, 70% carbohydrate), (b) control diet plus n-3 LCPUFA (108 mg/kg/day eicosapentaenoic acid plus 92 mg/kg/day docosahexaenoic acid), (c) HFD (60% fat, 20% protein, 20% carbohydrate), or (d) HFD plus n-3 LCPUFA for 12 weeks. Parameters of liver steatosis, glutathione status, protein carbonylation, and fatty acid analysis were determined, concomitantly with insulin resistance and serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 levels. HFD significantly increased total fat and triacylglyceride contents with macrovesicular steatosis, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum TNF-α, IL-1ß, and IL-6. Reduced and total liver glutathione contents were diminished by HFD, with higher GSSG/GSH ratio and protein carbonylation, n-3 LCPUFA depletion and elevated n-6/n-3 ratio over control values. These changes were either reduced or normalized to control values in animals subjected to HFD and n-3 LCPUFA, with significant increased hepatic total n-3 LCPUFA content and reduced n-6/n-3 ratio being observed after n-3 LCPUFA supplementation alone. So, repletion of liver n-3 LCPUFA levels by n-3 LCPUFA dietary supplementation in HFD obese mice reduces hepatic lipid content, with concomitant antioxidant and anti-inflammatory responses favouring insulin sensitivity.

Prevention of liver ischemia reperfusion injury by a combined thyroid hormone and fish oil protocol.

Several preconditioning strategies are used to prevent ischemia-reperfusion (IR) liver injury, a deleterious condition associated with tissue resection, transplantation or trauma. Although thyroid hormone (T3) administration exerts significant protection against liver IR injury in the rat, its clinical application is controversial due to possible adverse effects. Considering that prevention of liver IR injury has also been achieved by n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation to rats, we studied the effect of n-3 PUFA dietary supplementation plus a lower dose of T3 against IR injury. Male Sprague-Dawley rats receiving fish oil (300 mg/kg) for 3 days followed by a single intraperitoneal dose of 0.05 mg T3/kg were subjected to 1 h of ischemia followed by 20 h of reperfusion. Parameters of liver injury (serum transaminases, histology) and oxidative stress (liver contents of GSH and oxidized proteins) were correlated with fatty acid composition, NF-κB activity, and tumor necrosis factor-α (TNF-α) and haptoglobin expression. IR significantly modified liver histology; enhanced serum transaminases, TNF-α response or liver oxidative stress; and decreased liver NF-κB activity and haptoglobin expression. Although IR injury was not prevented by either n-3 PUFA supplementation or T3 administration, substantial decrease in liver injury and oxidative stress was achieved by the combined protocol, which also led to increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios, with recovery of NF-κB activity and TNF-α and haptoglobin expression. Prevention of liver IR injury achieved by a combined protocol of T3 and n-3 PUFA supplementation may represent a novel noninvasive preconditioning strategy with potential clinical application.

N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury.

Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to rats preconditions the liver against ischemia-reperfusion (IR) injury, with reduction of the enhanced nuclear factor-κB (NF-κB) functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation and interference with NF-κB activation. For this purpose we evaluated the formation of PPAR-α/NF-κBp65 complexes in relation to changes in PPAR-α activation, IκB-α phosphorylation and serum levels and expression of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion) or sham laparotomy (controls) in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) or isovolumetric amounts of saline (controls). Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology) was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-κB activation was paralleled by generation of PPAR-α/NF-κBp65 complexes, in concomitance with normalization of the IR-induced IκB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox) and Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-κB-controlled cytokines IL-lß and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-κB-controlled transcription of pro-inflammatory mediators. This effect is associated with the formation of PPAR-α/NF-κBp65 complexes and enhanced cytosolic IκB-α stability, as major preconditioning mechanisms induced by n-3 PUFA supplementation against IR liver injury.

Protection against in vivo liver ischemia-reperfusion injury by n-3 long-chain polyunsaturated fatty acids in the rat.

N-3 polyunsaturated fatty acids (n-3 PUFA) affect inflammatory processes. This study evaluated the effects of dietary supplementation with fish oil on hepatic ischemia-reperfusion (IR) injury in the rat. Parameters of liver injury (serum transaminases and histology) and oxidative stress (serum 8-isoprostanes and hepatic GSH and GSSG), were correlated with NF-kappaB DNA binding and FA composition and inflammatory cytokine release. N-3 PUFA supplementation significantly increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios. IR significantly modified liver histology and enhanced serum transaminases, 8-isoprotanes and inflammatory cytokines, with net reduction in liver GSH levels and net increment in those of GSSG. Early increase (3 h) and late reduction (20 h) in NF-kappaB activity was induced. All IR-induced changes were normalized by n-3 PUFA supplementation. In conclusion, prevention of liver IR-injury was achieved by n-3 PUFA supplementation, with suppression of oxidative stress and recovery of pro-inflammatory cytokine homeostasis and NF-kappaB functionality lost during IR.

Olive oil during pregnancy is associated with reduced wheezing during the first year of life of the offspring.

OBJECTIVE: To test the hypothesis that consuming Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy might be associated with less wheezing during the first year of the offspring's life. METHODS: A study was conducted in 1,409 infants (mean age, 16.6 +/- 2.5 months) attending healthy infant clinics in Spain. Dietary data of mothers' intake during pregnancy was collected by means of a parental food frequency questionnaire. Demographic information and data on wheezing during the first year of the offspring's life were also recorded. Infants were stratified according to any wheezing (42.2%) during the first year of life. RESULTS: In the univariate analysis, adherence to a Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy were both significantly associated with less wheezing during the first year of life. However, after multivariate analysis, only olive oil consumption during pregnancy remained associated with less wheezing in the studied period (aOR = 0.57 [95% CI = 0.4-0.9]); whereas male gender (1.8 [1.4-2.3]), day care attendance (2.15 [1.5-3.1]), maternal asthma (2.16 [1.3-3.6]), maternal smoking during pregnancy (1.83 [1.3-2.2]), infant eczema (1.95 [1.3-2.9]), and mould stains on the household walls (1.72 [1.2-2.5]) remained associated with wheezing. CONCLUSION: Our findings suggest a protective effect (primary prevention) of olive oil use during pregnancy on wheezing during the first year of the offspring's life.

Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins.

Preeclampsia (PE) is a multisystem disorder that remains a major cause of maternal and foetal morbidity and death. To date, no treatment has been found that prevents the development of the disease. Endothelial dysfunction is considered to underlie its clinical manifestations, such as maternal hypertension, proteinuria, and edema; however, the precise biochemical pathways involved remain unclear. A current hypothesis invokes the occurrence of oxidative stress as pathogenically important, as suggested by the fact that in PE, the placental and circulating levels of lipid peroxidation products (F2-isoprostanes and malondialdehyde [MDA]) are increased and endothelial cells are activated. A potential mechanism for endothelial dysfunction may occur via nuclear transcription factor kappa B (NF-kappaB) activation by oxidative stress. Alternatively, the idea that the antiangiogenic placental soluble fms-like tyrosine kinase 1 factor (sFlt1) is involved in the pathogenesis of this disease is just emerging; however, other pathophysiological events seem to precede its increased production. This review is focused on evidence providing a pathophysiological basis for the beneficial effect of early antioxidant therapy in the prevention of PE, mainly supported by the biological effects of vitamins C and E.