The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines

Mammary serine protease inhibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy)L-phenylalanylamido-2-deoxy-β-D-glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation has been determined in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP

A peptidyl-glucosamine derivative affects IKKα kinase activity in human chondrocytes

Nuclear factor-kappaB (NF-kappaB) transcription factor regulates several cell signaling pathways, such as differentiation and inflammation, which are both altered in osteoarthritis. Inhibitor kappaB kinase (IKK)alpha and IKKbeta are kinases involved in the activation of the NF-kappaB transcription factor. The aim of the present study was to determine the effects of glucosamine (GlcN), which is administered in the treatment of osteoarthritis, and of its 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-beta-D-glucose (NAPA) derivative on IKK kinases and, consequently, on NF-kappaB activation in human chondrocytes. The human chondrosarcoma cell line HTB-94 and human primary chondrocytes were stimulated with tumor necrosis factor (TNF)alpha after pre-treatment with GlcN or NAPA. Gene mRNA expression level was evaluated by real-time PCR. Inhibitor kappaB protein (IkappaB)alpha phosphorylation and p65 nuclear re-localization were analyzed by Western blotting; IKKalpha nuclear re-localization was also investigated by immunocytochemistry and Western blotting. IKK kinase activity was studied by in vitro kinase assay. After TNFalpha stimulation, the mRNA expression level of some of the genes under NF-kappaB control, such as interleukin (IL)-6 and IL-8, increased, while treatment with GlcN and NAPA reverted the effect. We investigated the possibility that GlcN and NAPA inhibit IKK kinase activity and found that NAPA inhibits the IKKalpha kinase activity, whereas GlcN does not. Interestingly, both GlcN and NAPA inhibit IKKalpha nuclear re-localization. Our results demonstrate that glucosamine and its peptidyl derivative can interfere with NF-kappaB signaling pathway by inhibiting IKKalpha activity in human chondrocytes. However, the mechanism of action of the two molecules is not completely overlapping. While NAPA can both specifically inhibit the IKKalpha kinase activity and IKKalpha nuclear re-localization, GlcN only acts on IKKalpha nuclear re-localization

Home Sweet Home: The Impact of Lifestyle on a Cat’s Approach to Impossible Tasks in the Home Environment

: Cat welfare is a topic of growing interest in the scientific literature. Although previous studies have focused on the effects of living style (i.e., indoor/outdoor) on cat welfare, there has been a noticeable dearth of analysis regarding the impact of lifestyle on cats' inclination and mode of communication with humans. Our research aimed to analyze the possible effect of lifestyle (e.g., living indoors only or indoor/outdoor) on cat-human communication. The cats were tested using the impossible task paradigm test, which consists of some solvable trials in which the subject learns to obtain a reward from an apparatus, followed by an impossible trial through blocking the apparatus. This procedure triggers a violation of expectations and is considered a useful tool for assessing both the decision-making process and the tendency to engage in social behaviors towards humans. A specific ethogram was followed to record the behavioral responses of the cats during the unsolvable trial. Our results show the effects of lifestyle and age on domestic cats, providing valuable insights into the factors that influence their social behaviors. Cats that can roam freely outdoors spent less time interacting with the apparatus compared to indoor-only cats. Additionally, roaming cats showed stress behaviors sooner following the expectancy of violation compared to indoor cats. The lifestyle of cats can influence their problem-solving approach while not affecting their willingness to interact with humans or their overall welfare. Future studies on this topic can be useful for improving the welfare of domestic cats

Development of a Spatial Discount Task to Measure Impulsive Choices in Dogs

Impulsive choices reflect an individual\u2019s tendency to prefer a smaller immediate reward over a larger delayed one. Here, we have developed a behavioural test which can be easily applied to assess impulsive choices in dogs. Dogs were trained to associate one of two equidistant locations with a larger food amount when a smaller amount was presented in the other location, then the smaller amount was placed systematically closer to the dog. Choices of the smaller amount, as a function of distance, were considered a measure of the dog\u2019s tendency to make impulsive choices. All dogs (N = 48) passed the learning phase and completed the entire assessment in under 1 h. Choice of the smaller food amount increased as this was placed closer to the dog. Choices were independent from food motivation, past training, and speed of learning the training phase; supporting the specificity of the procedure. Females showed a higher probability of making impulsive choices, in agreement with analogue sex differences found in human and rodent studies, and supporting the external validity of our assessment. Overall, the findings support the practical applicability and represent a first indication of the validity of this method, making it suitable for investigations into impulsivity in dogs

Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes

The aim of this study was to determine the effects of glucosamine on matrix metalloprotease (MMP) production, on mitogen-activated protein kinase (MAPK) phosphorylation, and on activator protein (AP)-1 transcription factor activation in human chondrocytes. The human immortalized cell line lbpva55 and healthy human chondrocytes (obtained from healthy donors) were subjected to challenge with 10 ng/ml IL-1β after pretreatment with 2.5 or 10 mmol/l glucosamine. MMP mRNA expression levels were evaluated using quantitative real-time PCR, and MMP protein production levels were evaluated in the culture supernatant using ELISA. MAPK phosphorylation was evaluated using Western blotting. AP-1 transcription factor activation was evaluated by measuring AP-1 DNA-binding activity. After IL-1β stimulation, levels of MMP-1, MMP-3 and MMP-13 production were markedly increased. Treatment with 2.5 and 10 mmol/l glucosamine reduced expression of these metalloproteases. MMP expression is regulated by transcription factors such as the AP-1 complex, which is activated by phosphorylated MAPKs. IL-1β stimulated phosphorylation of c-jun amino-terminal kinase, p38 MAPK and extracellular signal-regulated kinase-1/2. Glucosamine inhibited c-jun amino-terminal kinase and p38 phosphorylation, and consequently c-jun binding activity. These findings demonstrate, for the first time, that glucosamine inhibits IL-1β-stimulated MMP production in human chondrocytes by affecting MAPK phosphorylation

Sex differences in the behavioral responses of dogs exposed to human chemosignals of fear and happiness

This research focuses on sex differences in the behavioral patterns of dogs when they are exposed to human chemosignals (sweat) produced in happy and fear contexts. No age, breed or apparatus-directed behavior differences were found. However, when exposed to fear chemosignals, dogs' behavior towards their owners, and their stress signals lasted longer when compared to being exposed to happiness as well as control chemosignals. In the happy odor condition, females, in contrast to males, displayed a significantly higher interest to the stranger compared to their owner. In the fear condition, dogs spent more time with their owner compared to the stranger. Behaviors directed towards the door, indicative of exit interest, had a longer duration in the fear condition than the other two conditions. Female dogs revealed a significantly longer door-directed behavior in the fear condition compared to the control condition. Overall the data shows that the effect of exposure to human emotional chemosignals is not sex dependent for behaviors related to the apparatus, the owner or the stress behaviors; however, in the happiness condition, females showed a stronger tendency to interact with the stranger.info:eu-repo/semantics/publishedVersio

Puppies in the problem-solving paradigm: quick males and social females

We report an observational, double-blind study that examined puppies’ behaviors while engaged in solving an experimental food retrieval task (food retrieval task instrument: FRTI). The experimental setting included passive social distractors (i.e., the dog’s owner and a stranger). The focus was on how the social and physical environment shapes puppies’ behaviors according to sex. The dependent variables were the number of tasks solved on an apparatus (Performance Index) and the time required to solve the frst task (Speed). Sex and Stress were set as explanatory factors, and Social Interest, FRTI interactions, other behavior, and age as covariates. The main fndings were that male puppies solved the frst task faster than females. On the other hand, females displayed signifcantly more social interest and did so more rapidly than males. Males showed delayed task resolution. This study demonstrates sex diferences in a problem-solving task in dog puppies for the frst time, thus highlighting that sexually dimorphic behavioral diferences in problem-solving strategies develop early on during ontogenesis.info:eu-repo/semantics/publishedVersio

Parenting Desire and Minority Stress in Lesbians and Gay Men: A Mediation Framework

Despite the rapid increase in lesbian and gay (LG) people who desire and decide to become parents, LG childless individuals may encounter serious obstacles in the parenthood process, such as minority stress. Notwithstanding, the psychological processes by which prejudice events might affect the desire to become parents are still understudied. As an extension of the minority stress theory, the psychological mediation framework sheds light on these psychological processes, as it encompasses a more clinical view of stress. Within this framework, the current study aimed at assessing the role of prejudice events in affecting parenting desire in 290 childless Italian LG individuals (120 lesbians and 170 gay men), as well as the role of internalized heterosexism and sexual orientation concealment in mediating the relationship between prejudice events and parenting desire. The results suggest that only in lesbians prejudice events were negatively associated with parenting desire, and that sexual orientation concealment and internalized heterosexism were also negatively associated with parenting desire. Furthermore, sexual orientation concealment, and not internalized heterosexism, mediated the relationship between prejudice events and parenting desire in lesbians, but not gay men. The findings have important implications for clinical practice

Homophobia and transphobia in a sample of Movement Sciences students: Implications for physical education teachers and coaches

Gender and sexual stereotypes and prejudices are pervasive in sport contexts and used to preserve male superiority, relegating what is not masculine to a lower status. These stereotypes and biases are firmly rooted in sport also because they are constantly renewed and reinforced by athletic trainers, who may teach, along with sports practice, the underpinning heteronormative ideologies and values as well. The current study was aimed at exploring knowledge, opinions, and attitudes on gender and sexual diversity in sport among 181 Movement Sciences university students compared to 169 university students attending Psychology, Medicine, and Sociology. Participants answered questions related to gender and sexual diversity, homophobia, and transphobia and data were analyzed through student’s t-tests and linear regressions. Results indicated that Movement Sciences university students had a lower level of knowledge about sexual and gender diversity, and this was associated with higher levels of homophobic and transphobic attitudes. The results suggest the need to introduce specific training in degree courses to deconstruct stereotypes and prejudices around sexual and gender diversity

Pre-service teachers’ approaches to gender-nonconforming children in preschool and primary school: Clinical and educational implications

Corrective approaches taken by teachers towards gender nonconformity in childhood may increase the gender pressure that children feel, negatively affecting well-being and development. This study was aimed at assessing whether the approaches of 305 pre-service preschool and primary school teachers towards gender nonconformity in childhood are influenced by sexist and homophobic attitudes and feelings. The results indicated that the majority of the sample would adopt a supportive and affirmative approach towards gender nonconformity in childhood. Notwithstanding, the results also showed that sexism influenced the likelihood of adopting corrective approaches only to gender-nonconforming primary school children, whilst homophobia was positively associated with adoption of a corrective approach to gender nonconformity in both preschool and primary school children. Suggestions for educational and clinical practice are discussed