The influence of Castanea sativa Mill. flower extract on hormonally and chemically induced prostate cancer in a rat model.

Prostate cancer (PCa) is one of the most common cancers in men, with a huge impact on their health. The use of Castanea sativa Mill. flowers (CFs) in beverages has been reported, through ancestral claims, as having health benefits. In vitro research has evidenced the properties of CFs, such as antitumor and antioxidant activities. This study aimed to evaluate the effects of CF extract in an animal model of PCa. Forty male Wistar Unilever rats were randomly assigned to four groups: control, induced, control + CF, and induced + CF groups. Animals from the induced groups were exposed to a multistep protocol for PCa induction. The CF extract, rich in trigalloyl-HHDP-glucoside and obtained via decoction, was administered to the CF groups in drinking water (3 mg per animal per day) for 49 weeks. Animals were sacrificed at 61 weeks of age. Regarding the effects of CFs on dorsolateral prostate tumorigenesis, no significant differences were observed between the induced and induced + CF groups. However, animals exposed to the CF extract showed fewer inflammation areas on the dorsolateral prostate lobe than those not exposed to CF. Moreover, the CF extract alleviated the hepatic oxidative stress associated with the multistep protocol, resulting in lower levels of lipid peroxidation. These results suggest that CF extract has antioxidant and anti-inflammatory properties.

Stress response pathways in the male germ cells and gametes.

The unfolded protein response (UPR) is a conserved and essential cellular pathway involved in protein quality control that is activated in response to several cellular stressors such as diseases states, ageing, infection and toxins. The cytosol, endoplasmic reticulum (ER) and mitochondria are continuously exposed to new proteins and in situations of aberrant protein folding; one of three lines of defence may be activated: (i) heat-shock response, (ii) mitochondrial UPR and (iii) ER UPR. These pathways lead to different signal transduction mechanisms that activate or upregulate transcription factors that, in turn, regulate genes that increase the cell's ability to correct the conformation of poorly folded proteins or, ultimately, lead to apoptosis. Despite the recent progress in understanding such biological processes, few studies have focused on the implications of the UPR in male infertility, highlighting the need for a first approach concerning the presence of these components in the male reproductive system. In testis, there is a high rate of protein synthesis, and the UPR mechanisms are well described. However, the presence of these mechanisms in spermatozoa, apparently transcriptionally inactive cells, is contentious, and it is unclear how sperm cells deal with stress. Here, we review current concepts and mechanisms of the UPR and highlight the relevance of these stress response pathways in male fertility, especially the presence and functional activation of those components in male germinal cells and spermatozoa.

Isoform-specific GSK3A activity is negatively correlated with human sperm motility.

In mouse and bovine sperm, GSK3 activity is inversely proportional to motility. Targeted disruption of the GSK3A gene in testis results in normal spermatogenesis, but mature sperm present a reduced motility, rendering male mice infertile. On the other hand, GSK3B testis-specific KO is fertile. Yet in human sperm, an isoform-specific correlation between GSK3A and sperm motility was never established. In order to analyze GSK3 function in human sperm motility, normospermic and asthenozoospermic samples from adult males were used to correlate GSK3 expression and activity levels with human sperm motility profiles. Moreover, testicular and sperm GSK3 interactomes were identified using a yeast two-hybrid screen and coimmunoprecipitation, respectively. An extensive in-silico analysis of the GSK3 interactome was performed. The results proved that inhibited GSK3A (serine phosphorylated) presents a significant strong positive correlation (r = 0.822, P = 0.023) with the percentage of progressive human sperm, whereas inhibited GSK3B is not significantly correlated with sperm motility (r = 0.577, P = 0.175). The importance of GSK3 in human sperm motility was further reinforced by in-silico analysis of the GSK3 interactome, which revealed a high level of involvement of GSK3 interactors in sperm motility-related functions. The limitation of techniques used for GSK3 interactome identification can be a drawback, since none completely mimics the physiological environment. Our findings prove that human sperm motility relies on isoform-specific functions of GSK3A within this cell. Given the reported relevance of GSK3 protein-protein interactions in sperm motility, we hypothesized that they stand as potential targets for male contraceptive strategies based on sperm motility modulation.

Physicians versus surgeons. A pilot study on hand dexterity within a controlled population.

INTRODUCTION: Hand dexterity is defined as the innate or acquired capacity of performing any given procedure with one's hands. This study seeks the role of regular hand training on hand dexterity over time. Materials and Methods : Pilot study composed by two independent groups with 28 subjects each (surgeons and physicians), stratified according to gender and age. Measurement of hand dexterity using Lafayette's Purdue Pegboard through the sum of the first three exercises as well as the assembly exercise. No difference was found between groups in regards of gender, age, time of practice and hand size (p = 0.415 ; p = 0.225 ; p = 0.267 ; p = 0.937). Statistical significance was assumed when p < 0.050. RESULTS: Surgeons performed better but a statistically significant difference was not observed both on the -assembly score (p = 0.560) and three tests sum score (p = 0.244). The decay of dexterity over time happened in a homogeneous fashion in the surgeons' arm (p < 0.001 and p = 0.043) but not in the physicians' arm (p = 0.157 and p = 0.098). DISCUSSION: Surgeons seem to perform better than physicians in regards of hand dexterity, although no definitive conclusion was possible given our small sample. It is well known that aging worsens hand -dexterity, but our study suggests it happens much more homogeneously within surgeons.

The physiological relevance of protein phosphatase 1 and its interacting proteins to health and disease.

Protein phosphorylation is a major regulatory mechanism of signal transduction cascades in eukaryotic cells, catalysed by kinases and reversed by protein phosphatases (PPs). Sequencing of entire genomes has revealed that ~3% of all eukaryotic genes encode kinases or PPs. Surprisingly, there appear to be 2-5 times fewer PPs than kinases. Over the past two decades it has become apparent that the diversity of Ser/Thr-specific PPs (STPP) was achieved not only by the evolution of new catalytic subunits, but also by the ability of a single catalytic subunit to interact with multiple interacting proteins. PP1, a STPP, is involved in the control of important cellular mechanisms. Several isoforms of PP1 are known in mammals: PP1α, PP1ß and PP1γ. The various isoforms are highly similar, except for the N- and C-termini. The current view is that since PPs possess exquisite specificities in vivo, the key control mechanism must reside in the nature of the PP1 Interacting Protein (PIP) to which they bind. An increasing number of PIPs have been identified that are responsible for regulating the catalytic activity of PPs. Indeed, the diversity of such PIPs explains the need for relatively few catalytic subunit types, and makes them attractive targets for pharmacological intervention. This review will summarize the PIPs identified using the Yeast Two Hybrid methodology and alternative techniques, for instance bioinformatic and proteomic approaches. Further, it compiles 129 PP1-PIP relevant physiological interactions that are well documented in the literature. Finally, the use of PIPs as therapeutic targets will be addressed.

Understanding fatty acid metabolism through an active learning approach.

A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less emphasis is placed on transmitting information and the focus is shifted toward developing higher order thinking (analysis, synthesis, and evaluation). However, MALA should always involve clearly identified objectives and well-defined targets. Understanding fatty acid metabolism was one of the proposed goals of the Medical Biochemistry unit. To this end, students were challenged with a variety of learning strategies to develop skills associated with group conflict resolution, critical thinking, information access, and retrieval, as well as oral and written communication skills. Overall, students and learning facilitators were highly motivated by the diversity of learning activities, particularly due to the emphasis on correlating theoretical knowledge with human health and disease. As a quality control exercise, the students were asked to answer a questionnaire on their evaluation of the whole teaching/learning experience. Our initial analysis of the learning outcomes permits us to conclude that the approach undertaken yields results that surpass the traditional teaching methods.