The influence of physical exercise on oestrogen and androgen receptor expression in a chemically and hormonally-induced rat model of prostate cancer

Background: Oestrogen (ER) and androgen (AR) recep- tors play an important role in normal prostate development and are also implied in prostate cancer (PCa) development. Several studies suggested that physical activity may decrease the risk of PCa development and also changes sexual hor- mones and their receptors. This study aimed to evaluate the effects of physical exercise on ERα and AR expression in a rat model of chemically and hormonally-induced PCa. Materials and Methods: Fifty-five male Wistar Unilever rats of 12 weeks of age were randomly divided into four groups: control sedentary (n = 10), control exercised (n = 10), induced sedentary (n = 15) and induced exercised (n = 20). Animals from exercised groups started the exercise training in a treadmill (Treadmill Control LE 8710, Harvard Apparatus, USA), at the age of 8 weeks, for 35 weeks (5 days/week). The protocol for PCa induction started at 12 weeks of age and consisted of sequential administration of flutamide (50 mg/kg, TCI Chemicals), testosterone propion- ate (100 mg/kg, TCI Chemicals) and N-methyl-N-nitrosourea (30 mg/kg, Isopac®, Sigma Chemical Co.), followed by sub- cutaneous implants of crystalline testosterone. Animals were sacrificed at 61 weeks of age and a complete necropsy was performed. All experiments were approved by DGAV (no. 021326). Antibodies for Erα (1:500, clone 6F11, Novocastra) and AR (clone PG21, Merck Millipore) were used for the immunohistochemical study. The staining extension was evaluated in normal prostate tissue and in dorsolateral pros- tate lesions (hyperplasia, dysplasia, prostatic intraepithelial neoplasia (PIN) and microinvasive carcinoma) and assessed to five levels (0%, 75%), con- sidering the extension of immunopositive tissue. Data was analysed with SPSS 25.Results: The normal prostate tissue and dorsolateral prostate lesions of animals from all groups were immunopositive for Erα and AR. However, the groups showed high immunoposi- tivity for AR and low positivity for Erα ( 0.05). The malignant lesions (PIN and microinvasive carcinoma) showed lower AR expression when compared with normal prostate tissue in all groups. Conclusions: As expected, the AR expression was lower in malignant lesions. Inversely to that reported in other studies, the exercise training did not modify the ERα and AR expres- sion, which may be related to the duration and type of exer- cise performed

Effects of physical exercise in biochemical parameters and dorsolateral prostate lesions: data from a rat model of prostate cancer

Background: Prostate cancer (PCa) is among the most prevalent cancers worldwide. Physical exercise is widely recognized due to its beneficial effects. This study aimed to evaluate the effects of physical exercise on biochemical pa- rameters and in dorsolateral prostate lesions in a rat model of PCa. Materials and Methods: Ninety-five male Wistar Unilever rats were randomly divided into eight groups sacrificed at 35 (groups I) or 61 weeks of age (groups II): control sedentary groups (Cont+Sed I (n = 10); Cont+Sed II (n = 10)); induced sedentary group (PCa+Sed I (n = 10); PCa+Sed II (n = 15)); control exercised groups (Cont+EX I (n = 10); Cont+EX II (n = 10)) and induced exercised groups (PCa+EX I (n = 10); PCa+EX II (n = 20)). All procedures were approved (DGAV, no. 021326). Animals from exercised groups started the exer- cise program in a treadmill at 8 weeks of age, for 28 weeks or 53 weeks. The animals were trained 5 days/week, 60 min per day. Prostate lesions were induced at 12 weeks of age, with sequential administration of flutamide, testosterone propion- ate and N-methyl-N-nitrosourea, and subcutaneous implants of crystalline testosterone. Animals were sacrificed at 35 or 61 weeks of age. Peripheral blood of all animals was col- lected by intracardiac puncture. A complete necropsy was performed. The dorsolateral prostate tissues sections were processed for histological analysis. Data were analysed using SPSS 25. p 0.05). Dorsolateral prostate lesions were classified as dysplasia, prostatic intraep- ithelial neoplasia (PIN) and microinvasive carcinoma. The number of prostate lesions was higher in animals from groups II than in those from groups I, mainly in PCa+Sed II animals when compared with PCa+Sed I (p 0.05). Conclusions: Overall, the animals sacrificed at 61 weeks of age developed more dorsolateral prostate lesions than ani- mals sacrificed at 35 weeks of age, which may be related to a longer testosterone exposure

A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration

Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart.E.D. is supported by a VENI award 916-150-16 from the Netherlands Organization for Health Research and Development (ZonMW), an EMBO Long-term Fellowship (EMBO ALTF 848-2013) and a FP7 Marie Curie Intra-European Fellowship (Project number 627539). V.S.P. was funded by a fellowship from the FCT/ Ministério da Ciência, Tec-nologia e Inovação SFRH/BD/111799/2015. P.D.C.M. is an Established Investigator of the Dutch Heart Foundation. L.D.W. acknowledges support from the Dutch CardioVascular Alliance (ARENA-PRIME). L.D.W. was further supported by grant 311549 from the European Research Council (ERC), a VICI award 918-156-47 from the Dutch Research Council and Marie Sklodowska-Curie grant agreement no. 813716 (TRAIN-HEART)

Soil water-holding capacity and monodominance in Southern Amazon tropical forests

Background and aims: We explored the hypothesis that low soil water-holding capacity is the main factor driving the monodominance of Brosimum rubescens in a monodominant forest in Southern Amazonia. Tropical monodominant forests are rare ecosystems with low diversity and high dominance of a single tree species. The causes of this atypical condition are still poorly understood. Some studies have shown a relationship between monodominance and waterlogging or soil attributes, while others have concluded that edaphic factors have little or no explanatory value, but none has accounted for soil-moisture variation other than waterlogging. This study is the first to explicitly explore how low soil water-holding capacity influences the monodominance of tropical forests. Methods: We conducted in situ measurements of vertical soil moisture using electrical resistance collected over 1 year at 0–5; 35–40 and 75–80 cm depths in a B. rubescens monodominant forest and in an adjacent mixed-species forest in the Amazon-Cerrado transition zone, Brazil. Minimum leaf water potential (Ψmin) of the seven most common species, including B. rubescens, and soil water-holding capacity for both forests were determined. Results: The vertical soil moisture decay pattern was similar in both forests for all depths. However, the slightly higher water availability in the monodominant forest and Ψmin similarity between B. rubescens and nearby mixed forest species indicate that low water-availability does not cause the monodominance. Conclusions: We reject the hypothesis that monodominance of B. rubescens is primarily determined by low soil water-holding capacity, reinforcing the idea that monodominance in tropical forests is not determined by a single factor

Alcohol dehydrogenase activities and ethanol tolerance in Anastrepha (Diptera, Tephritidae) fruit-fly species and their hybrids

The ADH (alcohol dehydrogenase) system is one of the earliest known models of molecular evolution, and is still the most studied in Drosophila. Herein, we studied this model in the genus Anastrepha (Diptera, Tephritidae). Due to the remarkable advantages it presents, it is possible to cross species with different Adh genotypes and with different phenotype traits related to ethanol tolerance. The two species studied here each have a different number of Adh gene copies, whereby crosses generate polymorphisms in gene number and in composition of the genetic background. We measured certain traits related to ethanol metabolism and tolerance. ADH specific enzyme activity presented gene by environment interactions, and the larval protein content showed an additive pattern of inheritance, whilst ADH enzyme activity per larva presented a complex behavior that may be explained by epistatic effects. Regression models suggest that there are heritable factors acting on ethanol tolerance, which may be related to enzymatic activity of the ADHs and to larval mass, although a pronounced environmental effect on ethanol tolerance was also observed. By using these data, we speculated on the mechanisms of ethanol tolerance and its inheritance as well as of associated traits

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD