Evolutionary conservation of a regulative pathway of erythropoiesis in Poikilothermic vertebrates

Apoptosis, programmed cell death, plays a central role in haematopoiesis. Mature erythrocytes of non-mammalian vertebrates maintain a permanent nucleus; these cells can undergo apoptosis (eryptosis), as do other somatic cells of a given non-mammalian vertebrate. In this study, we have investigated the expression and subcellular distribution of Bcl-2, Bcl-XL and Bax proteins in the maturation phases and after X-ray irradiation of nucleated erythrocytes of Torpedo marmorata and Caretta caretta and the effect of X-ray irradiation on nucleated circulating erythrocytes of Torpedo marmorata. The cellular distribution of proteins was detected in erythrocytes by using immunocytochemistry at light microscopy and immunoelectron microscopy. The electrophoretic separation and immunoblotting of pro- and anti-apoptotic proteins of immature and mature erythroid cells was performed too, after X-ray irradiation of torpedoes. The results of the immunocytochemical analyses show an increase, in the expression level of Bax in mature as compared to young erythrocytes and a corresponding decrease of Bcl-2 and Bcl-XL. This maturation pattern of Bax, Bcl-2 and Bcl-XL was abrogated in X-ray irradiated torpedo erythrocytes. On the basis of these observations, Bax, Bcl-2 and Bcl-XL seems to play a role in the erythropoiesis of Torpedo marmorata Risso and in Caretta caretta. In conclusion, the same apoptotic proteins of somatic cells appear to be conserved in circulating nucleated erythrocytes thus suggesting to play a role in the maturation of these cells

Melatonin regulates mesenchymal stem cells differentiation : a review

none10Among the numerous functions of melatonin, the control of survival and differentiation of mesenchymal stem cells (MSCs) has been recently proposed. MSCs are a heterogeneous population of multipotent elements resident in tissues such as bone marrow, muscle, and adipose tissue, which are primarily involved in developmental and regeneration processes, gaining thus increasing interest for tissue repair and restoration therapeutic protocols. Receptor-dependent and receptor-independent responses to melatonin are suggested to occur in these cells. These involve antioxidant or redox-dependent functions of this indolamine as well as secondary effects resulting from autocrine and paracrine responses. Inflammatory cytokines and adipokines, proangiogenic/mitogenic stimuli, and other mediators that influence the differentiation processes may affect the survival and functional integrity of these mesenchymal precursor cells. In this scenario, melatonin seems to regulate signaling pathways that drive commitment and differentiation of MSC into osteogenic, chondrogenic, adipogenic, or myogenic lineages. Common pathways suggested to be involved as master regulators of these processes are the Wnt/b-catenin pathway, the MAPKs and the, TGF-b signaling. In this respect melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. These and other aspects of the physiological and pharmacological effects of melatonin as regulator of MSC are discussed in this review.openLuchetti, Francesca; Canonico, Barbara; Bartolini, Desiree; Arcangeletti, Marcella; Ciffolilli, Silvia; Murdolo, Giuseppe; Piroddi, Marta; Papa, Stefano; Reiter, Russel J.; Galli, FrancescoLuchetti, Francesca; Canonico, Barbara; Bartolini, Desiree; Arcangeletti, Marcella; Ciffolilli, Silvia; Murdolo, Giuseppe; Piroddi, Marta; Papa, Stefano; Reiter, Russel J.; Galli, Francesc

Melatonin reshapes the mitochondrial network and promotes intercellular mitochondrial transfer via tunneling nanotubes after ischemic-like injury in hippocampal HT22 cells

Mitochondrial dysfunction is considered one of the hallmarks of ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures that allow the exchange of proteins, soluble molecules, and organelles. Maintaining mitochondrial dynamics is crucial to cell function and survival. The present study aimed to assess the effects of melatonin on mitochondrial dynamics, TNT formation, and mitochondria transfer in HT22 cells exposed to oxygen/glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin treatment during the reoxygenation phase reduced mitochondrial reactive oxygen species (ROS) production, improved cell viability, and increased the expression of PGC1α and SIRT3. Melatonin also preserved the expression of the membrane translocase proteins TOM20 and TIM23, and of the matrix protein HSP60, which are involved in mitochondrial biogenesis. Moreover, it promoted mitochondrial fusion and enhanced the expression of MFN2 and OPA1. Remarkably, melatonin also fostered mitochondrial transfer between injured HT22 cells through TNT connections. These results provide new insights into the effect of melatonin on mitochondrial network reshaping and cell survival. Fostering TNTs formation represents a novel mechanism mediating the protective effect of melatonin in ischemia/reperfusion injury

How Porcine Acellular Dermal Matrix Influences the Development of the Breast Capsule 1 Year after Implantation: A Histopathological Analysis

Background: In prepectoral breast reconstruction (PPBR) the acellular dermal matrix (ADM)'s integration capacity into the tissue is known. The aim of this study was to analyze the effect of the ADM on development and composition of the peri-implant breast capsule in a dynamic setting of breast tissue expansion during two-stage prepectoral breast reconstruction.Methods: This is a prospective single-center study in which 50 patients who underwent mastectomy and breast reconstruction with prepectoral tissue expander and Braxon ADM (group A) and submuscular tissue expander (group B) were enrolled. One-year post implantation hematoxylin & eosin (H&E) staining and immunohistochemistry analyses were done on capsule tissue samples.Results: The analysis conducted on H&E-stained samples showed a significant reduction of cellular density and a decrease of the cellular infiltration in capsules of ADM-covered expanders compared with naked expander capsules (P < 0.05). The immunohistochemical analyses showed that group A capsules presented significantly less M1 CD68+ macrophages (P < 0.05), lower alfa-SMA expression levels, and a lower number of myofibroblasts (P < 0.05) compared with group B capsules. Presence of lymphatic vessels was minimally detected in both groups.Conclusions: The ADM presence around the prepectoral tissue expander influences the development of the peri-implant capsule, causing a significant reduction of the number of cells and inflammatory infiltrate, especially M1 macrophages and myofibroblasts. The ADM Braxon is therefore effective in creating a noninflamed capsule around the implant and in dynamic tissue conditions, and such an environment is maintained in time

Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice

Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs). Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD. Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD \u201cred-flags\u201d and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of \u201cred flags\u201d sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD. Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario. Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD

Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery

The burden of neoplastic diseases is widely recognized as a severe cause of mortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this scenario, targeting cancer cells apoptosis machinery has emerged as a relevant strategy, useful for tackling the emergence of drug resistance. On this basis, a small library of naturally inspired hybrid molecules was obtained by combining, through a click chemistry approach, "privileged" synthons such as curcumin scaffold and 1,2,3-triazole building block. Compound1, bearing apara-fluoro phenyl moiety, showed low-micromolar potency against T acute lymphoblastic leukemia cell growth. More in-depth biologic studies demonstrated, for this analog, cell death-inducing properties associated with its capability to simultaneously activate both the receptor and the mitochondrial apoptosis cascades. This peculiar behavior offers promises for achieving an expanded anticancer effect, namely intense cytotoxic response coupled with reduced predisposition of chemoresistance insurgence. Altogether, this study allowed the identification of compound1as a lead compound worth to be progressed as an anticancer drug candidate

Ventricular and atrial pressure—volume loops : analysis of the effects induced by right centrifugal pump assistance

The main indications for right ventricular assist device (RVAD) support are right heart failure after implantation of a left ventricular assist device (LVAD) or early graft failure following heart transplantation. We sought to study the effects induced by different RVAD connections when right ventricular elastance (EesRIGHT) was modified using numerical simulations based on atrial and ventricular pressure−volume analysis. We considered the effects induced by continuous-flow RVAD support on left/right ventricular/atrial loops when EesRIGHT changed from 0.3 to 0.8 mmHg/mL during in-series or parallel pump connection. Pump rotational speed was also addressed. Parallel RVAD support at 4000 rpm with EesRIGHT = 0.3 mmHg/mL generated percentage changes up to 60% for left ventricular pressure−volume area and external work; up to 20% for left ventricular ESV and up to 25% for left ventricular EDV; up to 50% change in left atrial pressure-volume area (PVLAL-A) and only a 3% change in right atrial pressure−volume area (PVLAR-A). Percentage variation was lower when EesRIGHT = 0.8 mmHg/mL. Early recognition of right ventricular failure followed by aggressive treatment is desirable, so as to achieve a more favourable outcome. RVAD support remains an option for advanced right ventricular failure, although the onset of major adverse events may preclude its use

Evaluation of speed-accuracy trade-off in a computer task to identify motor difficulties in individuals with Duchenne Muscular Dystrophy: A cross-sectional study

Introduction: Individuals with Duchenne Muscular Dystrophy (DMD) present with progressive loss of motor function which can impair both control of speed and accuracy of movement. Aim: to evaluate movement time during a task at various levels of difficulty and to verify whether the level of difficulty affects the speed and/ or accuracy during the task. Methods: the DMD group comprised of 17 individuals age matched with 17 individuals with typical development (TD group). The task evaluates the relationship between speed and accuracy, consisting of the execution of manual movements (using the mouse of the computer) aimed at a target at three different levels of difficulty (ID). Results: A MANOVA demonstrated statistically significant differences in dispersion data and intercept values between the groups with greater movement time in the DMD group. An ANOVA indicated differences between groups for ID, except for when there was a higher accuracy demand (higher ID). In the other IDs that required lower accuracy demand, individuals in the DMD group had significantly longer movement time when compared to the TD group. Conclusion: These results show that the TD and DMD did not differ in the higher ID, therefore it can be concluded that for those with DMD, motor performance is more affected by speed than accuracy of movement. What this paper adds? It is known that individuals with DMD have considerable motor deficits, however this paper shows that when the task involves higher accuracy compared with speed, people with DMD have performance similar to typically developed peers. This insight is a novel finding and can inform the rehabilitation team, to focus on training of speed, whilst maintaining accuracy for better execution of daily life tasks

Low-dose Oral Imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide. A phase II pilot study

none16noFraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, G; Gabrielli, A.Fraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, Gianluca; Gabrielli, Armand