Synthesis, Characterization, and Cytotoxicity Evaluation of Novel Water-Soluble Cationic Platinum(II) Organometallic Complexes with Phenanthroline and Imidazolic Ligands.

Platinum-based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water-soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1-C2H4OEt)(phen)] (1, phen=1,10-phenanthroline) precursor, specifically [Pt(NH3)(η1-C2H4OEt)(phen)]Cl (2), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl (3), and [Pt(1-hexyl-1H-benzo[d]imidazole)(η1-C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki-1), and normal human renal cells (HK-2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki-1) among the tested complexes, compared to healthy cells (HK-2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum-based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.

An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.

Neuroendocrine neoplasms (NENs) are a diverse group of malignancies with a shared phenotype but varying prognosis and response to current treatments. Based on their morphological features and rate of proliferation, NENs can be classified into two main groups with a distinct clinical behavior and response to treatment: (i) well-differentiated neuroendocrine tumors (NETs) or carcinoids (with a low proliferation rate), and (ii) poorly differentiated small- or large-cell neuroendocrine carcinomas (NECs) (with a high proliferation rate). For certain NENs (such as pancreatic tumors, higher-grade tumors, and those with DNA damage repair defects), chemotherapy is the main therapeutic approach. Among the different chemotherapic agents, cisplatin and carboplatin, in combination with etoposide, have shown the greatest efficacy in treating NECs compared to NETs. The cytotoxic effects of cisplatin and carboplatin are primarily due to their binding to DNA, which interferes with normal DNA transcription and/or replication. Consistent with this, NECs, which often have mutations in pathways involved in DNA repair (such as Rb, MDM2, BRCA, and PTEN), have a high response to platinum-based chemotherapy. Identifying mutations that affect molecular pathways involved in the initiation and progression of NENs can be crucial in predicting the response to platinum chemotherapy. This review aims to highlight targetable mutations that could serve as predictors of therapeutic response to platinum-based chemotherapy in NENs.

Creation of pacemaker remote monitoring networks between hospital and pharmacies during Covid-19 outbreak.

INTRODUCTION: Remote Monitoring (RM) of Cardiac Implantable Electronic Devices (CIEDs) is proven to be safe and efficient. It has been adopted in our center since years. At the time of the recent Covid-19 outbreak, we introduced and tested a collaborative organizational model, through a new RM device (Totem), creating a network with the surrounding territory and limiting CIED patients' presence in hospital. METHODS: We involved 4 neighbor pharmacies where Totem devices were installed; we called and informed 64 patients with Totem compatible pacemaker (PM) about the possibility to perform their PM follow-up (FU) in-pharmacy; 58 gave their consent and their data were inserted into our RM database. RESULTS: During an 18-month FU period, a total of 70 RM transmissions have been received: one alert of high atrial burden triggering a pharmacological optimization, one alert of high ventricular impedance leading to a new ventricular lead implantation and four alerts of elective replacement indicator. Fulfilled questionnaires revealed complete patient satisfaction. CONCLUSIONS: A collaborative network between our hospital and the surrounding territory to perform RM FUs of CIEDs during Covid-19 pandemic was feasible, leading to patient compliance and satisfaction and revealing important technical and clinical alerts.

The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review.

(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4/5 seems to display contradictory and inconsistent conclusions.

TGF-ß1 activates RSC96 Schwann cells migration and invasion through MMP-2 and MMP-9 activities.

Following peripheral nerve injury, remnant Schwann cells adopt a migratory phenotype and remodel the extracellular matrix allowing axonal regrowth. Although much evidence has demonstrated that TGF-ß1 promotes glioma cell motility and induces the expression of extracellular matrix proteins, the effects of TGF-ß1 on Schwann cell migration has not yet been studied. We therefore investigated the cellular effects and the signal transduction pathways evoked by TGF-ß1 in rattus norvegicus neuronal Schwann RSC96 cell. TGF-ß1 significantly increased migration and invasion of Schwann cells assessed by the wound-healing assay and by cell invasion assay. TGF-ß1-enhanced migration/invasion was blocked by inhibition of MMP-2 and MMP-9. Consistently, by real-time and western blot analyses, we demonstrated that TGF-ß1 increased MMP-2 and MMP-9 mRNA and protein levels. TGF-ß1 also increased MMPs activities in cell growth medium, as shown by gelatin zymography. The selective TGF-ß Type I receptor inhibitor SB431542 completely abrogated any effects by TGF-ß1. Indeed, TGF-ß1 Type I receptor activation provoked the cytosol-to-nucleus translocation of SMAD2 and SMAD3. SMAD2 knockdown by siRNA blocked MMP-2 induction and cell migration/invasion due to TGF-ß1. TGF-ß1 also provoked phosphorylation of MAPKs extracellular regulated kinase 1/2 and JNK1/2. Both MAPKs were upstream to p65/NF-kB inasmuch as both MAPKs' inhibitors PD98059 and SP600125 or their down-regulation by siRNA significantly blocked the TGF-ß1-induced nuclear translocation of p65/NF-kB. In addition, p65/NF-κB siRNA knockdown inhibited the effects of TGF-ß1 on both MMP-9 and cell migration/invasion. We conclude that TGF-ß1 controls RSC96 Schwann cell migration and invasion through MMP-2 and MMP-9 activities. MMP-2 is controlled by SMAD2 whilst MMP-9 is controlled via an ERK1/2-JNK1/2-NF-κB dependent pathway.

The effects of exercise training on lipid metabolism and coronary heart disease.

Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Thus, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood are a significant CHD risk factor, and several studies support the idea that aerobic exercise decreases CHD risk by partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver to favor its catabolism and excretion. This process prevents atherosclerosis, and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. In these and other ways, it more and more appears that regular exercise, nutrition, and strategies to modulate lipid profile should be viewed as an integrated whole. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers, including ApoB, ApoA1, and ApoB/ApoA1, in CHD risk.

The effects of training on hormonal concentrations in young soccer players.

To test the hypothesis that football training would be accompanied by physiological adaptations and hormonal changes, we analyzed the effects of a whole football season on physical fitness and hormonal concentrations in youth football players. Male football players (n = 29, age 16.51 ± 0.7 years) in a regional professional league and male healthy control subjects (n = 30, age 17.1 ± 1 years) participated to the study. Blood cortisol, testosterone, and growth hormone (hGH) concentrations were assayed before the beginning of the training period (T0), just after the training period (T1), at the middle of the season (T2), and at the end of the season (T3). In each period physical tests and anthropometric measurements were also performed. Results showed significant differences in basal values of cortisol, testosterone, and growth hormone (hGH) in the four time points evaluated (P < 0.01). In addition, the concentrations of hGH were higher in the soccer players group than in control subjects (P < 0.001). Between the start of the training period and the end of the football season significant differences were observed in the anthropometric characteristics and in the physical form of the football players. Furthermore, the hormonal status was significantly correlated with the indicators of the lower limb power (squat-jump [SqJ], and counter-movement-jump [CMJ]) and those of aerobic performance (Yo-Yo intermittent recovery test level 1 (YYIRT1) and maximal oxygen consumption (VO2max )).These data underscore the importance of establishing training protocols that present the potential to promote positive adaptations without, at the same time, provoking overtraining of young players.

ADP sensitizes ZL55 cells to the activity of cisplatin.

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor in which cisplatin therapy is commonly used, although its effectiveness is limited. It follows that research efforts dedicated to identify promising combinations that can synergistically kill cancer cells are needed. Because we recently demonstrated that ADP inhibits the proliferation of ZL55 cells, an MPM-derived cell line obtained from bioptic samples of asbestos-exposed patients. Our objective in this study was to investigate the hypothesis that ADP also potentiates the cytotoxic activity of cisplatin. Results show that in ZL55 cells ADP enhanced (a) the cytotoxicity of cisplatin by 12-fold, (b) the restraint of cell clonogenic potential cisplatin-mediated, and (c) the number of apoptotic cells. Cisplatin, but not ADP, caused caspases activation; nevertheless, poly(ADP-ribose) polymerase-1 was not only cleaved in cisplatin-treated cells but also in cells treated with ADP alone. Furthermore, ADP, but not cisplatin, decreased mTOR and 6SK phosphorylations. Both ADP and cisplatin increased p53 protein, but ADP was also able to enhance p53 messenger RNA. P53 silencing resulted in a very large decrement of cell death induced by ADP or by cisplatin and reverted ADP effects on mTOR/S6K phosphorylation, suggesting that activated p53 may act as a negative regulator of mTOR. Consistently, the inhibition of mTOR by rapamycin also sensitized cells to cisplatin, and the effects of cisplatin plus rapamycin were identical to those obtained with cisplatin plus ADP. These findings suggest that the combination of ADP and cisplatin may be a promising strategy for the clinical treatment of cisplatin-resistant MPM.

Inhibition of ZL55 cell proliferation by ADP via PKC-dependent signalling pathway.

Extracellular nucleotides can regulate cell proliferation in both normal and tumorigenic tissues. Here, we studied how extracellular nucleotides regulate the proliferation of ZL55 cells, a mesothelioma-derived cell line obtained from bioptic samples of asbestos-exposed patients. ADP and 2-MeS-ADP inhibited ZL55 cell proliferation, whereas ATP, UTP, and UDP were inactive. The nucleotide potency profile and the blockade of the ADP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 suggest that P2Y1 receptor controls ZL55 cell proliferation. The activation of P2Y1 receptor by ADP leads to activation of intracellular transduction pathways involving [Ca2+ ]i , PKC-δ/PKC-α, and MAPKs, ERK1/2 and JNK1/2. Cell treatment with ADP or 2-MeS-ADP also provokes the activation of p53, causing an accumulation of the G1 cyclin-dependent kinase inhibitors p21WAF1 and p27Kip . Inhibition of ZL55 cell proliferation by ADP was completely reversed by inhibiting MEK1/2, or JNK1/2, or PKC-δ, and PKC-α. Through the inhibition of ADP-activated transductional kinases it was found that PKC-δ was responsible for JNK1/2 activation. JNK1/2 has a role in transcriptional up-regulation of p53, p21WAF1/CIP1 , and p27kip1 . Conversely, the ADP-activated PKC-α provoked ERK1/2 phosphorylation. ERK1/2 increased p53 stabilization, required to G1 arrest of ZL55 cells. Concluding, the importance of the study is twofold: first, results shed light on the mechanism of cell cycle inhibition by ADP; second, results suggest that extracellular ADP may inhibit mesothelioma progression.

Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O'-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic ¹H-NMR Study.

The novel [Pt(O,O'-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of cis-[PtCl2(NH3)2], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A ¹H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC50 doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells.

CCL20 promotes migration and invasiveness of human cancerous breast epithelial cells in primary culture.

The relation between the tumor and its microenvironment is one of the most interesting and less understood issues. Recently, we showed a role of CCL20 chemokine in proning the healthy tissue neighboring the tumor to carcinogenesis. Besides, tumor-secreted CCL20 induced proliferation, migration, and EMT of healthy cells. In this context, we have studied here if CCL20 had effects on the migration of cancer cells and the intracellular pathways used in breast epithelial cells in primary culture. Using molecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated and involved in CCL20-induced tumor breast cell migration. CCL20 provoked a 2.5-fold increase of cell migration and invasion; CCL20 also enhanced MMP- 2 and MMP-9 mRNAs/protein expression and activities. Cell migration and invasiveness due to CCL20 significantly decreased when MMP-2 and MMP-9 were inhibited in CCL20-stimulated cells. CCL20 controlled MMP-2 expression through the JAK2/STAT3 pathway, while the expression of MMP-9 occurred by PKC-α that activated, consequently, c-Src, Akt, and finally NF-kB. These results reveal a role for CCL20 also in tumor breast cell and point to CCL20 as a novel therapeutic target in cancer.

Sex-Based Effects of Branched-Chain Amino Acids on Strength Training Performance and Body Composition.

BACKGROUND: Branched-chain amino acids (BCAAs) are widely studied for their effects on muscle recovery and performance. AIMS: This study examined the effects of BCAA supplementation on anthropometric data, physical performance, delayed onset muscle soreness (DOMS), and fatigue in recreational weightlifters. METHODS: The trial involved 100 participants (50 men and 50 women), randomized into BCAA and placebo groups. Subjects in the BCAA group took five daily capsules of 500 mg L-leucine, 250 mg L-isoleucine, and 250 mg L-valine for six months. A two-way ANOVA was used to analyze the main and interaction effects of sex and treatment. RESULTS: Notable findings include significant improvements in muscle recovery, as indicated by reduced DOMS, particularly in women who showed a decrement of 18.1 ± 9.4 mm compared to 0.8 ± 1.2 mm in the placebo group of a horizontal 100 mm line. Fatigue perception was also significantly lower in the BCAA group, with women reporting a greater decrease (2.6 ± 1.5 scores) compared to the placebo group (0.6 ± 0.7 scores). Strength gains were prominent, especially in men, with a 10% increase in bench press maximum observed in the BCAA group. The interaction between sex and treatment was significant, suggesting sex-specific responses to BCAA supplementation. CONCLUSIONS: These results underscore the effectiveness of BCAA supplementation in enhancing muscle recovery, reducing fatigue, and improving strength. This study also highlights sex-specific responses, with women benefiting more in terms of DOMS and fatigue reduction, while men experienced greater strength gains, suggesting a need for tailored supplementation strategies.

The Effects of Exergames on Physical Fitness, Body Composition and Enjoyment in Children: A Six-Month Intervention Study.

BACKGROUND/OBJECTIVES: Physical inactivity in children can lead to decreased physical fitness and reduced enjoyment of physical activity. This study aimed to evaluate the impact of exergaming on physical fitness, body composition and perceived enjoyment in elementary school children. METHODS: Sixty-four male students (mean age 9.5 years) were randomly assigned to an exergaming group (EG, n = 32), engaging in Kinect Adventures three times a week for six months, or a control group (CG, n = 32), which continued standard physical education. Assessments were conducted pre- and post-intervention, including anthropometric measures, physical fitness tests (standing long jump, countermovement jump, sit-and-reach, 20-m sprint), aerobic fitness (20-m shuttle run), and perceived enjoyment measured with the PACES scale. RESULTS: The EG demonstrated significant reductions in body weight, BMI, and relative fat mass compared to the CG (p < 0.01). Improvements in physical fitness were evident in EG, with increases in standing long jump distance (+12.8%; p < 0.0001), countermovement jump height (+65%, p < 0.0001), and flexibility (+75%; p < 0.0001). Aerobic fitness improved significantly in EG (+87.8m) compared to CG. Perceived enjoyment was notably higher in EG, especially at week three, compared to CG (69.3 ± 5.8 vs. 44.2 ± 11.6; p < 0.0001). CONCLUSIONS: Exergaming offers benefits for physical fitness and body composition in children, while also enhancing enjoyment. Incorporating exergames into physical education programs could be an effective strategy for addressing childhood obesity, improving physical skills, and increasing student enjoyment, encouraging long-term physical activity adherence.

The impact of adapted exercises in basketball on the perception of the difficulty and physical enjoyment of students with overweight.

The purpose of this study was to investigate the effect of the adapted basketball cycle on the perceived level of difficulty and physical enjoyment in girls and boys with overweight. Sixty-six students with overweight (aged 16-18 years) were randomly assigned to an experimental group (EG, n = 32 including 20 boys and 12 girls) and a control group (CG, n = 34; including 21 boys and 13 girls). Statistical analysis also showed that the levels of perceived difficulty decreased significantly after of seven-week of the adapted basketball cycle in both boys (Δ% = - 0.27; p < 0.001; and girls (Δ% = - 0.36; p < 0.001). There was no significant difference in students who participated in the traditional basketball cycle. A physical activity enjoyment Scale revealed that in girls, the level of enjoyment increased significantly (Δ% = + 0.27; P < 0.001) after an adapted basketball cycle. There was no significant change in physical enjoyment in boys EG (P = 0.808) and participants in the control groups. These results push us to opt more for adapted and motivational learning situations to make the teaching-learning process better, in students with overweight.

Correlation between impostor syndrome among doctoral students and supervisor empathy in Tunisia.

Introduction: The prevalence of impostor syndrome among PhD students has increased rapidly in recent years, having very negative effects on their mental and psychological health as well as on their doctoral journey. This exploratory study aims to examine whether there is a causal correlation between impostor syndrome among PhD students and empathy among supervisors. Methods: This study encompasses 562 doctoral students (300 females, 262 males) and 152 Tunisian supervisors (68 females, 84 males). Results: Employing ANOVA, significant influences on impostor syndrome emerge for gender, marital status, professional status, and the doctoral enrollment level (p < 0.001). Concurrently, supervisors' empathy is significantly affected by gender, marital status, and experience (p < 0.001). Linear regression establishes a noteworthy negative correlation (p = 0.045): a 1-unit increase in empathy correlates with a 0.122-unit decrease in impostor syndrome. Discussion: These findings underscore the intricate relationship between socio-professional factors, empathy, and impostor syndrome within the academic milieu, offering crucial insights for interventions and psychological support. The study aligns with the broader context of understanding mental health challenges in academia, emphasizing the imperative for ongoing support initiatives.

Harmonization of ANA testing challenge: quantification strategy to accurately predict end-point titers avoiding serial dilution.

Despite the advantages of automated systems for antinuclear antibody (ANA) analysis, the prediction of end-point titers avoiding serial dilutions is still in progress. The aims of this study were to set a conversion table providing discriminant ranges of fluorescence signal intensity values (FI) corresponding to the end-point titers and validate this tool in a real-life laboratory setting. Eight hundred ninety-four serum samples were analyzed for ANA using Image Navigator System. In order to classify FI into non-overlapping groups corresponding to conventional end-point titers, statistical discriminant analysis was used. Validation study was performed calculating agreement and error rates between visual readings and conversion table of 1119 routine ANA positive samples. Setting of FI ranges corresponding to the end-point titers for different staining patterns was computed. For samples showing single pattern, the overall agreement between visual readings and conversion table was 98.4% for all titers ranging from 1:160 to 1:2560, of which 68.0% had the same titer and 30.4% were within ± one titer difference. Concordance rates according to ANA patterns were as follows: (1) nuclear 98.4%, of which 67.0% had the same titer and 31.4% ± one titer; (2) cytoplasmic 100%, of which 72.7% had the same titer and 27.3% than ± one titer; (3) mitotic 66.6%, of which 33.3% had more ± one titer. Our study developed a quantification method for autoantibodies titers assessment based on just one single sample dilution instead of traditional serial dilution approach, providing significant advantages in routine laboratory in terms of reduction in hand-on time and harmonization of results.

CCL20 induces migration and proliferation on breast epithelial cells.

The communication between the tumor cells and the surrounding cells helps drive the process of tumor progression. Since the microenvironment of breast cancer includes CCL20 chemokine, the purpose of this study was to determine whether CCL20 modulates the physiology of healthy breast epithelial cells in areas adjacent to the tumor. Therefore, primary cultures of mammary cells taken from normal peritumoral areas were used. We assessed that breast cells expressed CCR6 CCL20 receptor. Using molecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated by CCR6 and involved in CCL20-induced breast cell proliferation and migration. The binding of 10 ng/ml CCL20 to CCR6 induced cell migration whilst higher concentrations (from 15 to 25 ng/ml) led to cell proliferation. CCL20 controlled cell migration and MMP-9 expression by PKC-alpha that activated Src, which caused the activation of downstream Akt, JNK, and NF-kB pathways. Furthermore, higher CCL20 concentrations increased cycE and decreased p27Kip expression ending in enhanced cell proliferation. Cell proliferation occurred through PKC-epsilon activation that transactivated EGFR and ERK1/2/MAPK pathway. Although activated by different CCL20 concentrations, these pathways function in parallel and crosstalk to some extent, inasmuch as Akt activation was responsible for ERK1/2 nuclear translocation and enhanced the transcription of of c-fos and c-myc, involved in cell proliferation. In summary, tumor cells exchange signals with the surrounding healthy cells modifying the extracellular matrix through enzyme secretion; thus, CCL20 might be a factor involved in the ontogeny of breast carcinoma.

Effects on Children's Physical and Mental Well-Being of a Physical-Activity-Based School Intervention Program: A Randomized Study.

This study aimed to evaluate the effectiveness of physically active breaks of a total duration of 10 min a day, introduced during curricular lessons, together with a 10 min physical activity intervention during the daily school recess period on obesity prevention, fitness, cognitive function, and psychological well-being in school-aged children. A sample of 310 children (139 boys vs. 171 girls), aged between 8 and 10 years (9.82 ± 0.51), was selected. Our strategy was implemented over a 6-month period and the participants were randomly assigned to either the intervention group (n = 157) or the non-intervention (control) group (n =153). In the intervention group, a significant decrease (p < 0.05) in body mass index, waist circumference, waist-height ratio, and relative body fat mass was achieved after the intervention (T1) compared to the values measured before intervention (T0); in the control group, no differences emerged between T0 and T1 for any of the parameters considered. We found a significant increase in the intervention group in standing long jump, Ruffier, and sit and reach test scores (p < 0.001 for all). At T0, cognitive test scores did not differ between the girls and boys or between the intervention and control groups; instead at T1, significant differences were observed in the two groups regarding the total number of responses and the concentration performance scores (p < 0.001). Consistently, in the intervention group, well-being levels significantly increased between T0 and T1 (p < 0.001). Finally, the intervention had significant effects on the children regardless of gender. We may therefore conclude that schools should create more opportunities for teachers and students to introduce intervention strategies to promote regular PA during school recess.

Immunolocalization of the AT-1R Ang II Receptor in Human Kidney Cancer.

This study aimed to evaluate AT1-R expression in normal and cancerous human kidneys, how these expressions are modified, and AT1-R functionality. AT-1R mRNA expression, determined by real-time PCR, was detected in all samples. AT-1R mRNA increased in well-differentiated cancer (G1, p < 0.01) and decreased 2.9-fold in undifferentiated cancer (G4, p < 0.001) compared with normal kidney tissues. Immunocytochemistry analysis showed that the AT-1R was expressed in the normal tubular epithelium. The glomerulus was also immunoreactive, and as expected, the smooth muscle cells of the vessel walls also expressed the receptor. A total of 35 out of 42 tumors were AT-1R positive, with the cell tumors showing varying numbers of immunoreactive cells, which were stained in a diffuse cytoplasmic and membranous pattern. Computer-assisted counting of the stained tumor cells showed that the number of AT-1R-positive cells increased in the well-differentiated cancers. The functionality of AT-1R was assessed in primary cultures of kidney epithelial cells obtained from three G3 kidney cancer tissues and corresponding histologically proven non-malignant tissue adjacent to the tumor. Indeed, Ang II stimulated, in a dose-dependent manner, the 24 h proliferation of normal kidney cells and cancer cells in the primary culture and phosphorylated extracellular regulated kinases 1 and 2. In conclusion, Ang II may be involved in the growth or function of neoplastic kidney tissue.

Integration of Obese Children in Physical Education Sessions: An Exploratory Study.

We investigated the effect of the role of the joker in children with obesity (OCs) on integration and physio-psychological responses during small-sided games (SSG) training programs. Sixteen OC students (age 13.8 ± 0.73 years) performed training programs consisting of two sessions a week for three weeks. The experimental protocol consisted of 16 teams of 4 children (3 of normal weight and 1 OC). The 16 teams were divided into 2 groups, one with an OC playing as the joker (SSG-J) and the other group with OC playing as non-joker (SSG-NJ). Maximum heart rates (HRmax), blood lactate concentration [La] and OMNI-Child perceived exertion were measured at the end of each SSG. A physical activity enjoyment Scale (PACES) was accomplished during physical activity for the evaluation of feelings in OCs. Additionally, the profile of mood states (POMS) was measured before and after the SSG-J and SSG-NJ programs. HRmax, [La], perceived exertion, and PACES scores were significantly higher after the SSG-J compared with SSG-NJ (increments of 6.4%, 31.7%, 19.5% and 18.1%, respectively). The score of the POMS variables was positively increased in the presence of jokers. The vigor score increased by 30%, while tension and total mood disturbance scores decreased by 27.6% and 4.5%, respectively. These findings suggest that the joker role could be effective in improving integration, physical enjoyment, physiological responses and mood states in OCs when a team game is used during PE sessions. PE teachers could then program joker exercises with the aim of improving OCs' physical commitment willingness to play.