Go for it! Exercising makes you happy and strong.

Despite it is generally recognized the beneficial role of physical activity, large portion of the population is physically inactive. Very alarmingly, the well-known gender gap in physical activity is constantly increasing. Several barriers obstacle women to perform physical activity although exercising would be of paramount importance for their health in particular during pregnancy and menopause. In addition to physical health benefits, physical activity may influence well-being and resilience, greatly impacting on quality of life. Here we explore the relationship between physical activity resilience and well-being in a group of 1107 female residents in the Metropolitan area of Naples.

The Frailty of the Invincible.

The COVID-19 pandemic has unveiled the frailty of our societies from too many points of view to look away. We need to understand why we were all caught unprepared. On the one hand, we have all short memories. As we forget too quickly, we were unable to recognize key factors influencing response and preparedness to public health threats. For many years, economic evaluation pushed governments all over the world to cut resources for public health systems, with COVID-19 pandemic the question arises: do we spend too much or too little on health care? What is the right amount to spend on health? Moreover, in many countries, the privatisation, or semi-privatisation, of healthcare may give rise to inequitable access to health care for everyone. Although COVID-19 is very "democratic", its consequences aren't. According to OECD, income inequality in OECD countries is at its highest level for the past half century. Three main causes have been recognized, technological revolution, globalization, and "financialisation". In this scenario, lockdown measures adopted to save lives are showing dramatic economic consequences. To address post COVID-19 reconstruction we need to go beyond GDP. As an economic measure this has many shortcomings in describing the real well-being of a country, and since what we measure affects what we do, new paradigms will have to guide the post COVID-19 reconstruction strategies, as the fate of countries and their citizens is at stake.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.

Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.

There is increasing evidence that diet plays a crucial role in age-related diseases and cancer. Oxidative stress is a conceivable link between diet and diseases, thus food antioxidants, counteracting the damage caused by oxidation, are potential tools for fight age-related diseases and cancer. Resveratrol (RSV), a polyphenolic antioxidant from grapes, has gained enormous attention particularly because of its ability to induce growth arrest and apoptosis in cancer cells, and it has been proposed as both chemopreventive and therapeutic agent for cancer and other diseases. Even though the effects of RSV have been studied in prostate cancer cells and animal models, little is known about its effects on normal cells and tissues. To address this issue, we have investigated the effects of RSV on EPN cells, a human non-transformed prostate cell line, focusing on the relationship between RSV and p66Shc, a redox enzyme whose activities strikingly intersect those of RSV. p66Shc activity is regulated by phosphorylation of serine 36 (Ser36) and has been related to mitochondrial oxidative stress, apoptosis induction, regulation of cell proliferation and migration. Here we show that RSV inhibits adhesion, proliferation and migration of EPN cells, and that these effects are associated to induction of dose- and time-dependent p66Shc-Ser36 phosphorylation and ERK1/2 de-phosphorylation. Moreover, we found that RSV is able to activate also p52Shc, another member of the Shc protein family. These data show that RSV affects non-transformed prostate epithelial cells and suggest that Shc proteins may be key contributors of RSV effects on prostate cells.

PATZ1 gene has a critical role in the spermatogenesis and testicular tumours.

PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. To gain insights into its biological role, we generated mice lacking the PATZ1 gene. Male PATZ1(-/-) mice were unfertile, suggesting a crucial role of this gene in spermatogenesis. Consistently, most of adult testes from these mice showed only few spermatocytes, associated with increased apoptosis, and complete absence of spermatids and spermatozoa, with the subsequent loss of tubular structure. The analysis of PATZ1 expression, by northern blot, western blot and immunohistochemistry, revealed its presence in Sertoli cells and, among the germ cells, exclusively in the spermatogonia. Since PATZ1 has been indicated as a potential tumour suppressor gene, we also looked at its expression in tumours deriving from testicular germ cells (TGCTs). Although expression of PATZ1 protein was increased in these tumours, it was delocalized in the cytoplasm, suggesting an impaired function. These results indicate that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization could be associated to the development of TGCTs.

Detection of high-mobility group proteins A1 and A2 represents a valid diagnostic marker in post-pubertal testicular germ cell tumours.

The high-mobility group A (HMGA) non-histone chromosomal proteins HMGA1 and HMGA2 are architectural factors. They are abundantly expressed during embryogenesis and in most malignant neoplasias, whereas their expression is low or absent in normal adult tissues. Their over-expression is known to have a causal role in cellular neoplastic transformation. Previous studies from our group have shown that their expression is restricted to specific germinal cells. In this study we have evaluated, by immunohistochemistry, the expression of HMGA1 and HMGA2 in a series of post-pubertal testicular tumours of different histological types, including 30 seminomas, 15 teratomas, 15 embryonal carcinomas and 10 mixed germinal tumours with a prominent yolk sac tumour component. HMGA1 protein expression was detected in all seminomas and embryonal carcinomas analysed, but not in teratomas or yolk sac carcinomas. Conversely, HMGA2 was present only in embryonal carcinomas and yolk sac carcinomas, but not in seminomas or teratomas. The immunohistochemical data were further confirmed by Western blot and, at the mRNA level, by RT-PCR analyses. These findings indicate that HMGA1 and HMGA2 are differently expressed with respect to the state of differentiation of testicular germ cell tumours (TGCTs), with over-expression of both proteins in pluripotential embryonal carcinoma cells and loss of expression of HMGA1 in yolk sac tumours and of both proteins in the mature adult tissue of teratoma areas. Therefore, the different profiles of HMGA1 and HMGA2 protein expression could represent a valuable diagnostic tool in some cases in which the histological differential diagnosis is problematic.

cAMP induced modifications of HOX D gene expression in prostate cells allow the identification of a chromosomal area involved in vivo with neuroendocrine differentiation of human advanced prostate cancers.

The acquisition of epithelial-neuroendocrine differentiation (ND) is a peculiarity of human advanced, androgen-independent, prostate cancers. The HOX genes are a network of transcription factors controlling embryonal development and playing an important role in crucial adult eukaryotic cell functions. The molecular organization of this 39-gene network is unique in the genome and probably acts by regulating phenotype cell identity. The expression patterns of the HOX gene network in human prostate cell phenotypes, representing different stages of prostate physiology and prostate cancer progression, make it possible to discriminate between different human prostate cell lines and to identify loci and paralogous groups harboring the HOX genes mostly involved in prostate organogenesis and cancerogenesis. Exposure of prostate epithelial phenotypes to cAMP alters the expression of lumbo-sacral HOX D genes located on the chromosomal region 2q31-33 where the cAMP effector genes CREB1, CREB2, and cAMP-GEFII are present. Interestingly, this same chromosomal area harbors: (i) a global cis-regulatory DNA control region able to coordinate the expression of HOX D and contiguous phylogenetically unrelated genes; (ii) a prostate specific ncRNA gene associated with high-risk prostate cancer (PCGEM1); (iii) a series of neurogenic-related genes involved with epithelial-neuronal cell conversion. We report the expression of neurexin 1, Neuro D1, dlx1, and dlx2 in untreated and cAMP treated epithelial prostate cells. The in vivo expression of Neuro D1 in human advanced prostate cancers correlate with the state of tumor differentiation as measured by Gleason score. Thus, we suggest that the chromosomal area 2q 31-33 might be involved in the epithelial-ND characteristic of human advanced prostate cancers.

Aurora B expression in normal testis and seminomas.

Aurora/Ipl1-related kinases are a conserved family of proteins that have multiple functions during mitotic progression. High levels of Aurora kinases are characteristic of rapidly dividing cells and tumours. Aurora B encodes a protein that associates with condensing chromatin, concentrates at centromeres, and then relocates onto the central spindle at anaphase. In this study the expression and the localisation of Aurora B throughout germinal epithelial progression in normal testis and its neoplastic counterpart were analysed. Immunocytochemistry and RT-PCR analysis of mouse germinal epithelium cells showed the presence of Aurora B in spermatogonia and occasionally in spermatocytes. Western blot analysis revealed the typical Aurora B isoform ( approximately 41 kDa) in the same cellular types. A similar distribution was observed in human testis by immunohistochemistry. Moreover, the distribution and the expression of Aurora B were investigated in neoplasms derived from germ cells. Surgical samples of seminomas were analysed, and a high percentage of Aurora B positive cells (51%) was detected; the expression of Aurora B was significantly related to the MIB-1 proliferation marker (R=0.816). The data presented here demonstrate that Aurora B expression occurs in spermatogonial division. Furthermore, our results indicate that the expression of Aurora B is a consistent feature of human seminomas.

RET/PTC1 oncogene signaling in PC Cl 3 thyroid cells requires the small GTP-binding protein Rho.

Thyroid papillary carcinomas are characterized by RET/PTC rearrangements that cause the tyrosine kinase domain of the RET receptor to fuse with N-terminal sequences encoded by heterologous genes. This results in the aberrant expression of a ligand-independent and constitutively active RET kinase. We analysed actin reorganization induced by the RET/PTC1 oncogene in PC Cl 3 rat thyroid epithelial cells. Differently from oncogenes Src, Ras and Raf, RET/PTC1 caused actin filaments to form prominent stress fibers. Moreover, stress fibers were identified in human thyroid papillary carcinoma cell lines harboring RET/PTC1 rearrangements but not in thyroid carcinoma cells negative for RET/PTC rearrangements. RET/MEN 2A, a constitutively active but unrearranged membrane-bound RET oncoprotein, did not induce stress fibers in PC Cl 3 cells. Induction of stress fibers by RET/PTC1 was restricted to thyroid cells; it did not occur in NIH3T3 fibroblasts or MCF7 mammary cells. RET/PTC1-mediated stress fiber formation depended on Rho but not Rac small GTPase activity. In addition, inhibition of Rho, but not of Rac, caused apoptosis of RET/PTC1-expressing thyroid cells. We conclude that Rho is implicated in the actin reorganization and cell survival mediated by the chimeric RET/PTC1 oncogene in thyroid epithelial cells, both phenotypes being cell type- and oncogene type-specific.

Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma.

Deregulated expression of inhibitors of apoptosis (programmed cell death) may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to therapy. In this study, we investigated the potential expression and prognostic significance of the apoptosis inhibitor survivin in squamous cell carcinoma (SCC). A series of 135 cases of SCC including 46 oral SCC and 89 cutaneous SCC was analyzed for survivin expression by immunohistochemistry and Western blotting. Survivin was found in 57 cases (64%) of skin SCC and 26 cases (56%) of oral SCC, with weighted survivin scores ranging from 1 to 12. In contrast, normal oral epithelium, normal skin epithelium, and skin annexa did not express survivin. Survivin expression significantly (P < 0.05) segregated with high-grade and undifferentiated tumors with size >1.5 cm and invariably associated with lymph node metastasis. These data suggest that survivin expression may predictively identify cases of SCC with more aggressive and invasive clinical phenotype, potentially warranting closer follow-up protocols.

Variations of proline-rich kinase Pyk2 expression correlate with prostate cancer progression.

Proline-rich kinase 2 (Pyk2), also known as CAKbeta (cell adhesion kinase beta), is a cytoplasmic tyrosine kinase that is structurally related to focal adhesion kinase. Pyk2 is expressed in different cell types including brain cells, fibroblasts, platelets, and other hemopoietic cells. Pyk2 is rapidly tyrosine phosphorylated in response to diverse extracellular signals acting via different post receptor pathways. We have investigated whether this protein kinase is functionally expressed in normal and neoplastic prostate tissues. In this study, we demonstrate that Pyk2 is expressed only in normal epithelial prostate tissue and in benign prostatic hyperplasia, whereas its expression progressively declines with an increasing grade of malignancy of prostate cancer.

Estradiol-induced mitogen-activated protein kinase (extracellular signal-regulated kinase 1 and 2) activity in the frog (Rana esculenta) testis.

Several lines of evidence support a key role of estradiol-17beta (E(2)) in male fertility. We have used a non-mammalian vertebrate model, the frog Rana esculenta, to investigate the regulation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity in the testis during the annual sexual cycle and to study whether E(2 )exerts a role in spermatogenesis through the regulation of ERK1/2 activity. ERK1/2 proteins are present in the cytoplasm and nucleus of the primary and secondary spermatogonia (SPG), and in the nucleus of primary spermatocytes. The annual E(2) profile shows a progressive increase during active spermatogenesis with a peak in the month of June. In parallel, ERK1/2 are highly phosphorylated during the period of active spermatogenesis (from April to July) compared with the regressive period (September/October) and winter stasis (from November to March). E(2) treatment induces the proliferation of primary SPG, possibly via the activation of ERK1/2, and this effect is counteracted by the anti-estrogen ICI 182-780.

Hypericin photosensitization of tumor and metastatic cell lines of human prostate.

We have investigated the photoactivating effect of hypericin on two cancer cell lines: PC-3, a prostatic adenocarcinoma non-responsive to androgen therapy and LNCaP, a lymphonodal metastasis of prostate carcinoma responsive to androgen therapy. The two cell lines are incubated for 24 h with hypericin at concentrations ranging from 0.001 to 0.3 microg/ml in cell culture medium. The cells are irradiated at 599 nm (fluence = 11 J/cm2) using a dye laser pumped by an argon laser. Hypericin exerts phototoxic effects on both cell lines, while it does not produce toxic effects in the absence of irradiation. These results suggest that photodynamic therapy (PDT) with hypericin could be an alternative approach to the treatment of prostatic tumors, and could be beneficial in tumors that are non-responsive to androgen therapy.

Association between the expression of E1A oncogene and increased sensitivity to growth inhibition induced by sustained levels of cAMP in rat thyroid cells.

OBJECTIVE: The aim of this study was to investigate: (i) whether a persistent increase of cAMP interferes with the proliferation of transformed thyroid cells, and (ii) whether the degree of malignancy is correlated with the sensitivity to a transient and/or sustained increase in intracellular cAMP levels. DESIGN AND METHODS: To address these questions we used thyroid cell lines transformed with E1A oncogene from adenoviruses 5 (PC E1A cell line) or 2 (PC HE4 cell line), or infected with the polyoma murine leukemia virus (PC PyMLV cell line) carrying the middle T gene of the polyoma virus, or, finally, expressing both E1A and PyMLV. These cell lines present various degrees of malignancy: PC EIA and PC HE4 cells are not tumorigenic; PC PyMLV cells induce non-invasive tumors after a long latency period; and PC EIA+PyMLV cells are highly tumorigenic. RESULTS AND CONCLUSIONS: Thyroid cell proliferation required the transient increase of intracellular cAMP levels, while persistent elevation of cAMP blocked the proliferation of normal thyroid PC Cl 3 cells and of PC Cl 3 cells transformed by a variety of different oncogenes. In addition, sustained levels of cAMP induced apoptosis in cells carrying the adenovirus EIA oncogene, but not in cells transformed with other oncogenes or in the wild-type PC Cl 3 cells. Furthermore, middle T gene of the polyoma virus seemed to afford protection only from apoptosis induced by cAMP when middle T is present in thyroid cells along with the E1A gene.

C-Jun phosphorylation (Ser-63) in the testis of the lizard, Podarcis s. sicula.

Proto-oncogenes play an important role in the regulation of cellular growth and differentiation. C-Jun activity has been studied in the testis of a non mammalian vertebrate, the lizard Podarcis s. sicula, during two different periods: winter stasis and the breeding season. C-Jun protein was localized by immunocytochemistry in the cytoplasm of the spermatogonia (SPG) and stage I and II spermatocytes (SPC) during the winter stasis (from December until March), while the protein was present in the nuclei of the same cells during the active spermatogenic period (April/May). The different localization of c-Jun has been confirmed by Western blot and immunoprecipitation analysis. In addition, when Jun is present in the nuclear compartment, it is phosphorylated on Ser-63 and is complexed with Fos protein. These data suggest that the nuclear localization of the Jun protein in the SPG and stage I and II SPC, with strong phosphorylation on Ser-63 during the breeding period, could be the signal of increasing transcriptional activity in the lizard testis.

Hypertensive left ventricular remodeling and ACE-gene polymorphism.

OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.

Endogenous insulin-like growth factors regulate the proliferation of TSH-independent mutants derived from FRTL5 cells.

TSH-independent mutant clones (M cells) derived from FRTL5 cells, proliferate vigorously in the absence of TSH. The growth of M cells is stimulated by IGF-I in a dose-dependent fashion, but it is not influenced by TSH. Sm1.2, an antibody against IGF-I cross-reacting with IGF-II, significantly decreases basal DNA synthesis in the M cells. Binding of 125I-IGF-I to M cells is significantly lower than that to FRTL5 cells. M cells produce in their culture medium IGF-like peptides which appear to influence their basal DNA synthesis and the availability of type I receptors to bind exogenous IGF-I.

Thyroid cell transformation inhibits the expression of a novel rat protein tyrosine phosphatase.

We have isolated a rat thyroid cDNA encoding a novel rat receptor-type tyrosine phosphatase protein. This gene, on the basis of its homology to another tyrosine phosphatase, the recently isolated human DEP-1/HPTPeta, has been named r-PTPeta. In rat thyroid cells the r-PTPeta gene acts as a differentiation marker. Indeed, the block of thyroid cell differentiation induced by viral and cellular oncogenes is associated with the inhibition or marked reduction of the expression of this gene, and its expression is positively regulated by thyrotropin, the physiological stimulator of thyroid cell growth.

Deletion polymorphism of angiotensin-converting enzyme gene and left ventricular hypertrophy in southern Italian patients.

OBJECTIVES: This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI). BACKGROUND: The renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy. METHODS: The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient. RESULTS: Left ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02). CONCLUSIONS: Our data show that the LVMI was significantly enhanced in patients with the DD genotype.

Sustained versus transient cyclic AMP intracellular levels: effect on thyrotropin-dependent growth of thyroid cells.

Cyclic AMP (cAMP) is the second messenger that stimulates growth and differentiation of thyroid cells, which are dependent upon thyrotropin for the initiation of the cell cycle. Treatment of thyroid cells with phosphodiesterase inhibitors, such as 1-methyl-3-isobutylxanthine (IBMX), RO-20-1724, or aminophylline, induces persistent levels of cAMP and blocks cell proliferation. IBMX-treated cells are arrested at the G1-S border, but removal of the drug allows cell growth to resume. The inhibiting effect of IBMX is dose dependent, and the phase of the cell cycle is irrelevant. These data indicate that prolonged and steady accumulation of cAMP blocks the cell cycle in thyroid cells.