Geometria responsiva

Il progetto industriale, così come quello architettonico, manifesta un’attenzione crescente verso comportamenti di tipo “responsivo”. Gli oggetti, sia nella piccola scala del Design, sia nella più grande scala dell’architettura, sono sempre più frequentemente dotati di un’intelligenza digitale, una logica comportamentale che consente loro di interagire con le persone che li fruiscono. Gli oggetti e gli spazi a carattere “responsivo” caratterizzeranno senza dubbio il prossimo futuro e questo processo di trasformazione riguarderà in modo particolare anche la forma e dunque la geometria che la forma stessa astrae e descrive. La modellazione parametrica è un valido ausilio in questo processo, ma il progettista, più del solito, dovrà necessariamente confrontarsi con la geometria. Lo studio qui illustrato sperimenta la parametrizzazione finalizzata alla trasformazione dinamica di superfici piane in superfici coniche

Modulation of miR-204 expression during chondrogenesis

RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes' maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes' maturation

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy

Two novel C-terminus RUNX2 mutations in two cleidocranial dysplasia (CCD) patients impairing p53 expression

Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the RUNX2 gene have been identified in most CCD patients. Transcription factor RUNX2, the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of RUNX2 mutations in CCD patients, we investigated RUNX2 gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how RUNX2 mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, RUNX2 mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of RUNX2 mutations in CCD patients and suggests that an in-depth analysis of the RUNX2-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects

The impact of biologic therapy for moderate-to-severe psoriasis on the immune responses to SARS-CoV2 infection and vaccination

Dear Editor, we explored the impact of biologics and conventional therapies for psoriasis on humoral and T-cellular responses to SARS-CoV-2 infection and vaccine. The study (EUDRA 2020-004965-37 Humanitas ICH Ethic Committee) was conducted at the Istituto Clinico Humanitas-Rozzano, Milan, and at the University of Verona, Italy. The enrolled patients were affected by moderate-to-severe psoriasis and were divided into two groups: those who had developed COVID-19 infection (group 1, n=95) and those who underwent COVID-19 vaccination (group 2, n=77

Effects of a 4400 km ultra-cycling non-competitive race and related training on body composition and circulating progenitors differentiation

Background: NorthCape4000 (NC4000) is the most participated ultra-endurance cycling race. Eight healthy male Caucasian amateur cyclists were evaluated: (a) before starting the preparation period; (b) in the week preceding NC4000 (after the training period); (c) after NC4000 race, with the aim to identify the effects of ultra-cycling on body composition, aerobic capacity and biochemical parameters as well as on the differentiation of progenitor cells. Methods: Bioelectrical impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA) assessed body composition; cardiopulmonary exercise test (CPET) evaluated aerobic capacity. Differentiation of circulating progenitor cells was evaluated by analyzing the modulation in the expression of relevant transcription factors. In addition, in vitro experiments were performed to investigate the effects of sera of NC4000 participants on adipogenesis and myogenesis. The effects of NC4000 sera on Sestrins and Sirtuin modulation and the promotion of brown adipogenesis in progenitor cells was investigated as well. Two-tailed Student's paired-test was used to perform statistical analyses. Results: We observed fat mass decrease after training as well as after NC4000 performance; we also recorded that vitamin D and lipid profiles were affected by ultra-cycling. In addition, our findings demonstrated that post-NC4000 participant's pooled sera exerted a positive effect in stimulating myogenesis and in inducing brown adipogenesis in progenitor cells. Conclusions: The training program and Ultra-cycling lead to beneficial effects on body composition and biochemical lipid parameters, as well as changes in differentiation of progenitor cells, with significant increases in brown adipogenesis and in MYOD levels

Physical activity modulates miRNAs levels and enhances MYOD expression in myoblasts

Stem cells functions are regulated by different factors and non-conding RNAs, such as microRNA. MiRNAsplay an important role in modulating the expression of genes involved in the commitment and differentiation of progenitor cells. MiRNAs are post transcriptional regulators which may be modulated by physical exercise. MiRNAs, by regulating different signaling pathways, play an important role in myogenesis as well as in muscle activity. MiRNAs quantification may be considered for evaluating physical performance or muscle recovery. With the aim to identify specific miRNAs potentially involved in myogenesis and modulated by physical activity, we investigated miRNAs expression following physical performance in Peripheral Blood Mononuclear Cells (PBMCs) and in sera of half marathon (HM) runnners. The effect of runners sera on Myogenesis in in vitro cellular models was also explored. Therefore, we performed Microarray Analysis and Real Time PCR assays, as well as in vitro cell cultures analysis to investigate myogenic differentiation. Our data demonstrated gender-specific expression patterns of PBMC miRNAs before physical performance. In particular, miR223-3p, miR26b-5p, miR150-5p and miR15-5p expression was higher, while miR7a-5p and miR7i-5p expression was lower in females compared to males. After HM, miR152-3p, miR143-3p, miR27a-3p levels increased while miR30b-3p decreased in both females and males: circulating miRNAs mirrored these modulations. Furthermore, we also observed that the addition of post-HM participants sera to cell cultures exerted a positive effect in stimulating myogenesis. In conclusion, our data suggest that physical activity induces the modulation of myogenesis-associated miRNAs in bothfemales and males, despite the gender-associated different expression of certain miRNAs, Noteworthy, these findings might be useful for evaluating potential targets for microRNA based-therapies in diseases affecting the myogenic stem cells population

Fisetin: an integrated approach to identify a strategy promoting osteogenesis

Flavonoids may modulate the bone formation process. Among flavonoids, fisetin is known to counteract tumor growth, osteoarthritis, and rheumatoid arthritis. In addition, fisetin prevents inflammation-induced bone loss. In order to evaluate its favorable use in osteogenesis, we assayed fisetin supplementation in both in vitro and in vivo models and gathered information on nanoparticle-mediated delivery of fisetin in vitro and in a microfluidic system. Real-time RT-PCR, Western blotting, and nanoparticle synthesis were performed to evaluate the effects of fisetin in vitro, in the zebrafish model, and in ex vivo samples. Our results demonstrated that fisetin at 2.5 μM concentration promotes bone formation in vitro and mineralization in the zebrafish model. In addition, we found that fisetin stimulates osteoblast maturation in cell cultures obtained from cleidocranial dysplasia patients. Remarkably, PLGA nanoparticles increased fisetin stability and, consequently, its stimulating effects on RUNX2 and its downstream gene SP7 expression. Therefore, our findings demonstrated the positive effects of fisetin on osteogenesis and suggest that patients affected by skeletal diseases, both of genetic and metabolic origins, may actually benefit from fisetin supplementation

Can the Multidimensional Prognostic Index (MPI) be a predictive instrument for mortality in older adult liver transplant candidates?

PurposeThe most recent guidelines recommend that selection of liver transplant recipient patients be guided by a multidimensional approach that includes frailty assessment. Different scales have been developed to identify frail patients and determine their prognosis, but the data on older adult candidates are still inconclusive. The aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older people patients being evaluated for liver transplantation.MethodsThis retrospective study was conducted on 68 patients > 70 years being followed at the University Hospital of Padua in 2018. Clinical information on each patient, Model For End-Stage Liver Disease (MELD), Body Mass Index (BMI), Activities of Daily Living (ADL), Mini Nutritional Assessment (MNA), LFI, MPI, and date-of-death, were recorded. The observational period was 3 years.ResultsWe studied 68 individuals (25 women), with a mean age 72.21 & PLUSMN; 1.64 years. Twenty-five (36.2%) patients died during the observational period. ROC curve analysis showed both MPI and LFI to be good predictors of mortality (AUC 0.7, p = 0.007, and AUC 0.689, p = 0.015, respectively). MELD (HR 1.99, p = 0.001), BMI (HR 2.34, p = 0.001), and poor ADL (HR 3.34, p = 0.04) were risk factors for mortality in these patients, while male sex (HR 0.1, p = 0.01) and high MNA scores (HR 0.57, p = 0.01) were protective factors.ConclusionOur study confirmed the prognostic value of MPI in older adult patients awaiting liver transplantation. In this cohort, good nutritional status and male sex were protective factors, while high MELD and BMI scores and poor functional status were risk factors.Key summary pointsAimThe aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older adult patients being evaluated for liver transplantationFindingsOn the 68 patients studied, ROC curve analysis showed that MPI was similar or slightly better than LFI as predictor of mortality (AUC 0.7, p=0.007, and AUC 0.689, p=0.015, respectively).MessageIn older people patients listed for liver transplantation, MPI is as good a prognostic tool as LFI for predicting mortality