Poly-L-lactic acid beta-tricalcium phosphate screws: a preliminary in vivo biocompatibility study.

The aim of this study is to assess the biocompatibility of two types of Poly-L-lactic acid (PLLA) screws (with either hydroxiapatite (HA) or β-tricalcium phosphate (β-TCP)) implanted in the left femur of four sheep euthanized at 42, 50, 57 and 84 days after surgery. Titanium screws were also implanted for comparison purposes. No signs of inflammation were seen in the 240 specimens. A rating of "+/-"for macrophages and "-"for neutrophils was assigned to all specimens. All specimens were assigned a rating which ranged from "+/-" to "+++" for fibroblasts and osteoblasts. The presence of macrophages, neutrophils and fibroblasts/osteoblasts was not statistically different for the four implantation periods. PLLA implants with β-TCP have a biocompatibility comparable to PLLA implants with HA

Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans

n/

The Large Magellanic Cloud globular cluster NGC 1866: new data, new models, new analysis

We present a new deep (down to V ~ 24) photometry of a wide region (6'x 6') around the LMC globular cluster NGC1866: our sample is complete, down to 3 mag below the brightest MS star. Detailed comparisons with various theoretical scenarios using models computed with the evolutionary code FRANEC have been done reaching the following conclusions: both standard models (i.e. computed by adopting the Schwarzschild criterion to fix the border of the convective core) and models with an enlarged convective core (overshooting) lead to a fair fit of the MS but are not able to reproduce the luminosity and/or the number of He burning giants. Models including a fraction of 30% of binaries leads to a good fit both to the MS luminosity function and to the He clump, if standards models are considered, for a visual distance modulus (m-M)v = 18.8, age t ~ 100 Myr and mass function slope alpha ~ 2.4, thus largely removing the "classical" discrepancy between observed and predicted number of stars in the He burning clump. The fit obtained with models computed with an enlarged convective core gets worse when a binary component is taken into account, because the presence of binary systems increases the existing discrepancy between the observed and predicted clump luminosity. As a consequence of this analysis, we conclude that the next step towards a proper understanding of NGC 1866, and similar clusters, must include the accurate determination of the frequency of binary systems that will be hopefully performed with the incoming Cycle 8 HST observations of NGC~1866.Comment: AASTEX 5.0, 33 pages, 35 figures. Two tables of photometry and full resolution figures available on request from the first author ([email protected]). Accepted on A

Plasticity, exudation and microbiome-association of the root system of Pellitory-of-the-wall plants grown in environments impaired in iron availability

The investigation of the adaptive strategies of wild plant species to extreme environments is a challenging issue, which favors the identification of new traits for plant resilience. We investigated different traits which characterize the root-soil interaction of Parietaria judaica, a wild plant species commonly known as "Pellitory-of-the-wall". P. judaica adopts the acidification-reduction strategy (Strategy I) for iron (Fe) acquisition from soil, and it can complete its life cycle in highly calcareous environments without any symptoms of chlorosis. In a field-to-lab approach, the microbiome associated with P. judaica roots was analyzed in spontaneous plants harvested from an urban environment consisting in an extremely calcareous habitat. Also, the phenolics and carboxylates content and root plasticity and exudation were analyzed in P. judaica plants grown under three different controlled conditions mimicking the effect of calcareous environments on Fe availability: results show that P. judaica differentially modulates root plasticity under different Fe availability-impaired conditions, and that it induces, to a high extent, the exudation of caffeoylquinic acid derivatives under calcareous conditions, positively impacting Fe solubility.13n

Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponectin and leptin (p-value < 0.001 for both). However, only in women VFth and EFth significantly correlated between them (p = 0.013) and also with leptin (p < 0.001 for both) and hs-CRP (p = 0.005 and p = 0.028, respectively). Linear regression confirmed an independent association of both leptin and hs-CRP with VFth in women, also after adjustment for age and MetS (p = 0.012 and 0.007, respectively). In conclusion, men and women present differences in epicardial fat deposition and systemic inflammation. An intriguing association between visceral/epicardial fat depots and chronic low-grade inflammation also emerged. In women Although a further validation in larger studies is needed, these findings suggest a critical role of sex in stratification of obese/dysmetabolic patients

Secreted Gal-3BP is a novel promising target for non-internalizing Antibody–Drug Conjugates

Abstract Galectin-3-binding protein (Gal-3BP) has been identified as a cancer and metastasis-associated, secreted protein that is expressed by the large majority of cancers. The present study describes a special type of non-internalizing antibody-drug-conjugates that specifically target Gal-3BP. Here, we show that the humanized 1959 antibody, which specifically recognizes secreted Gal-3BP, selectively localized around tumor but not normal cells. A site specific disulfide linkage with thiol-maytansinoids to unpaired cysteine residues of 1959, resulting in a drug-antibody ratio of 2, yielded an ADC product, which cured A375m melanoma bearing mice. ADC products based on the non-internalizing 1959 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed and secreted by several cancers, while being present at low levels in most normal adult tissues

USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer

Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.Fil: Rossi, Fabiana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Enriqué Steinberg, Juliana Haydeé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Calvo Roitberg, Ezequiel Hernán. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Joshi, Molishree Umesh. University of Colorado; Estados UnidosFil: Pandey, Ahwan. No especifíca;Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dufrusine, Beatrice. University of Chieti-Pescara; ItaliaFil: Buglioni, Simonetta. Regina Elena Cancer Institute; ItaliaFil: De Laurenzi, Vincenzo. University of Chieti-Pescara; ItaliaFil: Sala, Gianluca. University of Chieti-Pescara; ItaliaFil: Lattanzio, Rossano. University of Chieti-Pescara; ItaliaFil: Espinosa, Joaquín Maximiliano. University of Colorado; Estados UnidosFil: Rossi, Mario. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin

Estimating Glomerular Filtration Rate in Older People

We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting

Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51

: Breast cancer (BC) is the second cause of cancer-related deceases in the worldwide female population. Despite the successful treatment advances, 25% of BC develops resistance to current therapeutic regimens, thereby remaining a major hurdle for patient management. Current therapies, targeting the molecular events underpinning the adaptive resistance, still require effort to improve BC treatment. Using BC sphere cells (BCSphCs) as a model, here we showed that BC stem-like cells express high levels of Myc, which requires the presence of the multifunctional DNA/RNA binding protein Sam68 for the DNA-damage repair. Analysis of a cohort of BC patients displayed that Sam68 is an independent negative factor correlated with the progression of the disease. Genetic inhibition of Sam68 caused a defect in PARP-induced PAR chain synthesis upon DNA-damaging insults, resulting in cell death of TNBC cells. In contrast, BC stem-like cells were able to survive due to an upregulation of Rad51. Importantly, the inhibition of Rad51 showed synthetic lethal effect with the silencing of Sam68, hampering the cell viability of patient-derived BCSphCs and stabilizing the growth of tumor xenografts, including those TNBC carrying BRCA mutation. Moreover, the analysis of Myc, Sam68 and Rad51 expression demarcated a signature of a poor outcome in a large cohort of BC patients. Thus, our findings suggest the importance of targeting Sam68-PARP1 axis and Rad51 as potential therapeutic candidates to counteract the expansion of BC cells with an aggressive phenotype

USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer

Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada