Ovarian actions of resveratrol Ortega, Israel; Duleba, Antoni J.
Annals of the New York Academy of Sciences,
August 2015, Letnik:
1348, Številka:
1
Journal Article
Recenzirano
Resveratrol, a natural polyphenol found in grapes, berries, and medicinal plants, exhibits antioxidant and anti‐inflammatory activities and has been proposed to be a longevity‐prolonging agent. There ...is also growing evidence that resveratrol has cardioprotective properties and beneficial effects on both glucose and lipid metabolism. Recently, several studies have examined the use of resveratrol as a therapeutic agent to treat numerous pathological and metabolic disorders. Herein, we present insights into the mechanisms of action, biological effects, and current evidence of actions of resveratrol on the ovary. In vitro, resveratrol inhibits proliferation and androgen production by theca‐interstitial cells. Resveratrol also exerts a cytostatic, but not cytotoxic, effect on granulosa cells, while decreasing aromatization and vascular endothelial growth factor expression. In vivo, resveratrol treatment reduced the size of adipocytes and improved estrus cyclicity in the previously acyclic rat model of polycystic ovary syndrome (PCOS). In addition, resveratrol increased the ovarian follicular reserve and prolonged the ovarian life span in rats. Taken together, resveratrol emerges as a potential therapeutic agent to treat conditions associated with androgen excess, such as PCOS. The efficacy of resveratrol in the treatment of gynecological conditions requires further investigation.
This work examines aquaculture-related activities in the commercial exploitation of fish reproduction. Fisheries' problem of maximizing utility is modeled for the state of Puebla, Mexico, to ...determine optimal fish production. The problem of maximizing utility subject to the fish production function is solved using an approach based on Euler's equation. The theoretical results are then applied, using data on aquaculture production and tilapia sales prices in the state of Puebla, Mexico. A logarithmic regression is used to approximate the utility function. The optimal fishing production and utility functions are thus explicitly obtained. Furthermore, this work shows how to obtain greater profits from the amount of fish that can be extracted without reducing the fish population.
The article deals with the extensions of discrete-time games with infinite time horizon and their application in a fuzzy context to fishery models. The criteria for these games are the total ...discounted utility and the average utility in a fishing problem. However, in the fuzzy case, game theory is not the best way to represent a real fishing problem because players do not always have enough information to accurately estimate their utility in the context of fishing. For this reason, in this paper, trapezoidal-type fuzzy utility values are considered for a fishing model, and the terms of the Nash equilibrium are given in the fuzzy context, i.e., this equilibrium is represented using the partial order of the α-cuts of the fuzzy numbers; to the best of the authors’ knowledge, there is no work with this type of treatment. To obtain each equilibrium, a suitable fully determined fuzzy game is used in combination with the dynamic programming technique applied to this game in the context of fishing. The main results are (i) the Nash equilibria of the fuzzy games coincide with the Nash equilibria of the nonfuzzy games and are explicitly determined in a fishery model and (ii) the values of the fuzzy games are of trapezoidal type and are also explicitly given in the fishery model.
The article concerns a study of infinite-horizon deterministic Markov decision processes (MDPs) for which the fuzzy environment will be presented through considering these MDPs with both fuzzy ...rewards and fuzzy costs. Specifically, these rewards and costs will be assumed of a suitable trapezoidal type. For both classes of MDPs, i.e., MDPs with fuzzy rewards and MDPs with fuzzy costs, the fuzzy total discounted function will be taken into account as the objective function, and the corresponding optimal decision problems will be considered with respect to the max order of the fuzzy numbers. For each optimal decision problem, the optimal policy and the optimal value function are related and obtained as a solution of a convenient standard MDP (i.e., a standard MDP is an MDP with a non-fuzzy reward function or a non-fuzzy cost function). Moreover, an economic growth model (EGM), a deterministic version of the linear-quadratic model (LQM), and an optimal consumption model (OCM) in order to clarify the theory presented are given, and it is remarked that these models have uncountable state spaces, and the corresponding non-fuzzy version of both the EGM and the OCM has an unbounded reward function, and the corresponding non-fuzzy version of the LQM has an unbounded cost function.
Breast cancer (BC) is the leading cause of cancer-related death in women in the world. Since tumor cells employ autophagy as a survival pathway, it has been proposed that autophagy inhibition could ...be beneficial for cancer treatment. There are several onging clinical trials where autophagy is being inhibited (using chloroquine, CQ or hydroxychloroquine, HCQ) along with chemotherapy with promising results. However, there is also in vitro evidence in which autophagy inhibition can induce epithelial to mesenchymal transition (EMT) in cancer cells, indicating that, at least in some cases, this strategy could be detrimental for cancer patients. In this study, we found that the genetic inhibition of autophagy primed cells for EMT by inducing a decrease in E-cadherin protein levels, while CQ treatment decreased E-cadherin levels, induced morphological changes related to EMT, increased EMT-related transcription factor (EMT-TF) expression and migration in estrogen receptor positive (ER +) BC cell lines. Importantly, CQ treatment increased intracellular reactive oxygen species (ROS) which induced the secretion of macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine related to malignancy. Both ROS production and MIF secretion were responsible for the mesenchymal morphology and increased migratory capacity induced by CQ. Our results indicate that CQ treatment increased malignancy by inducing ROS production, MIF secretion and EMT and suggest that autophagy inhibition in ER + BC patients might have detrimental effects. Our data indicates that a careful selection of patients should be performed in order to determine who will benefit the most from autophagy inhibition with available pharmacological agents for the treatment of breast cancer.
A severe complication of allogeneic hematopoietic stem cell transplantation (HSCT) is graft failure (GF). Among others, donor‐specific anti‐HLA antibodies (DSA) are associated with graft rejection ...after allogeneic or haploidentical transplantation in adults. Knowledge of DSA and pediatric recipients is limited. Hence, we aimed to generate more information about the presence of DSA (pre‐ and post‐HSCT) and the clinical outcomes (graft rejection and poor function) in children. We identified DSA in 27% of the patients. We observed a higher frequency (50%) of DSA‐bearing patients with a benign disease diagnosis than those diagnosed with leukemia (16.66%). We observed graft rejection in one patient (with DSA against two alleles of HLA class I molecules) and poor function in three recipients during the first 30 days after HSCT in the absence of DSA. The presence of donor and nondonor HLA‐specific antibodies decreased substantially after transplantation. After the transplant, we identified two patients with DSA specific for HLA class I molecules (independent of clinical relevance), and four recipients showed PGF in the absence of DSA. We were unable to establish any association between the presence of DSA and a clinical outcome: graft failure or prevalence of viral infection.
Patients with end-stage renal disease have very high mortality. In individuals on hemodialysis, cardiovascular deaths account for ~50% of all deaths in this population, mostly due to arrhythmia. To ...determine the causes of these arrhythmic deaths is essential in order to adopt preventive strategies. The main objective of this study was to investigate whether, the presence of QTc interval alterations, from electrolyte abnormalities or presence of rare genetic variants, could have a relationship with sudden arrhythmogenic deaths in end-stage renal disease patients.
We recorded the pre- and post-dialysis QTc interval in 111 patients undergoing hemodialysis. In 47 of them, we analyzed 24 SCD-related genes including the most prevalent genes associated with long QT syndrome using a custom resequencing panel.
We found a positive although not significant association between the presence of long QTc and mortality in a subset of end-stage renal disease patients. In addition, in five patients with long QTc only after dialysis (21.7%) we detected rare potentially pathogenic genetic variants. Three out of these five carriers subsequently died suddenly.
Genetic background may be determinant in the risk of sudden cardiac death in these patients. We recommend evaluating the QTc interval before and after hemodialysis, and performing a genetic analysis of individuals with long QTc after hemodialysis.
Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis and for providing nutrients for survival in response to stress conditions. Recently, ...autophagy has been shown to be important for the secretion of diverse proteins involved in inflammation, intercellular signaling, and cancer progression. The role of autophagy in cancer depends on the stage of tumorigenesis, serving a tumor-suppressor role before transformation and a tumor-survival function once a tumor is established. We review recent evidence demonstrating the complexity of autophagy regulation during cancer, considering the interaction of autophagy with protein secretion pathways. Autophagy manipulation during cancer treatment is likely to affect protein secretion andinter-cellular signaling either to the neighboring cancer cells or to the antitumoral immune response. This will be an important consideration during cancer therapy since several clinical trials are trying to manipulate autophagy in combination with chemotherapy for the treatment of diverse types of cancers.
Polycystic ovary syndrome is characterized by theca-interstitial hyperplasia and increased expression of steroidogenic genes, leading to excessive androgen production. Resveratrol, a natural ...polyphenol, promotes apoptosis and reduces rat theca-interstitial cell growth, in part by inhibiting the mevalonate pathway and decreasing the availability of substrates of isoprenylation farnesyl-pyrophosphate (FPP) and geranylgeranyl-pyrophosphate (GGPP). This study evaluated the effect of resveratrol on rat theca-interstitial cell steroidogenesis. Because resveratrol may activate sirtuins, this study also investigated whether steroidogenesis was affected by sirtuin inhibitors (nicotinamide, sirtinol). Theca-interstitial cells were cultured with or without resveratrol (1–10 μm), GGPP (30 μm), FPP (30 μm), nicotinamide (1 mm), and/or sirtinol (10 μm). Resveratrol did not affect progesterone levels but reduced androgen production in a concentration-dependent fashion (androstenedione by up to 78% and androsterone by up to 76%). This inhibitory effect correlated with a decrease in mRNA expression of genes regulating androgen production, especially Cyp17a1 (by up to 73%). GGPP and FPP had no effect on androgen levels and Cyp17a1 mRNA levels and did not alter the effects induced by resveratrol. Similarly, sirtuin inhibitors did not reverse resveratrol-induced inhibition of steroidogenesis. However, resveratrol decreased activity of serine-threonine kinase/protein kinase B pathway, a cell-signaling pathway involved in ovarian steroidogenesis. The present findings indicate that resveratrol reduces androgen production primarily by inhibiting Cyp17a1 mRNA expression, and this inhibition may be mediated, in part, by blocking the activity of the serine-threonine kinase/protein kinase B pathway. These findings may be of clinical relevance to conditions associated with excessive production of androgens by theca cells, such as polycystic ovary syndrome.
During coral calcification in massive scleractinian corals, a double annual banding of different densities (high- and low-density) is formed in their skeletons, which can provide a retrospective ...record of growth and the influence of environmental conditions on the coral's lifespan. Evidence indicates that during the last decades, the reduction in coral calcification rate is attributed to the combination of global stress factors such as Sea Surface Temperature (SST) and local anthropic stressors. Yet, coral growth trajectories can vary between regions and coral species, where remote locations of coral reefs can act as natural laboratories, as they are far from the harmful effects of direct anthropogenic stressors. The present study reports historical chronology over a 24-year period (1992-2016) of coral extension rate (cm yr.sup.-1 ), skeletal density (g cm.sup.-3 ), and calcification rate (g cm.sup.-2 yr.sup.-1) of the reef-building coral Orbicella faveolata at the remote reef Cayo Arenas, Campeche Bank, in the south-eastern Gulf of Mexico. The relationships between the three sclerochronological features show that O. faveolata uses its calcification resources to build denser skeletons. Chronological trends indicate that coral extension increased, skeletal density and calcification rate decreased (33% calcification rate) over time. The results reveal that despite the remoteness of the locality the maximum SST has been increased, and the coral calcification rate decreased over time. If the temperature continues to rise, there is a conceivable risk of experiencing a decline in reef-building coral species. This scenario, in turn, could pose a significant threat, endangering not only the framework of coral reefs but also their ecological functionality, even within remote Atlantic reef ecosystems.
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