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A stem cell is defined as an unspecialized cell that can both self-renew and give rise to differentiated progeny. In particular stem cells can divide to generate at least one cell that retains the stem cell identity, and can also give rise to progenitors, or precursor cells, which typically differentiate into tissue-specific cell types. Stem cells are derived from embryonic, fetal, or adult tissue and are broadly categorized accordingly. Recent advances in regenerative medicine support the development of new and emerging areas of integrative research including stem cells, gene- and cell-based therapies, and tissue engineering. The type of human cells, the use of growth factors and cytokines to stimulate the production, and growth and function of cells, along with the cell sources, have shown a significant therapeutic impact to date and represent a rapidly grown area of regenerative medicine.

Background: The increased prevalence of cardiovascular disease (CVD) indicates a demand for novel therapeutic approaches. Proteome analysis of vascular tissues from animal models and humans with CVD could lead to the identification of novel druggable targets. Methods: LC-MS/MS analysis of thoracic aortas from three mouse models of non-diabetic and diabetic (streptozotocin (STZ)-induced) atherosclerosis followed by bioinformatics/pathway analysis was performed. Selected findings were confirmed by proteomics analysis of human vessels from patients with CVD as well as in vitro studies (migration, proliferation, angiogenesis assays) using endothelial (HUVEC) cells. Findings: Comparative tissue proteomics of low density lipoprotein receptor deficient (Ldlr−/−) and diabetic Ldlr−/− (Ldlr−/−STZ) with wild type (WT) animals led to the identification of 284 differentially expressed proteins in both models. Among them, 177 proteins were also differentially expressed in diabetic apolipoprotein E deficient (ApoE−/−STZ) mice, suggesting expression changes associated with atherosclerosis independent of the model used. These proteins recapitulated the hallmarks of atherosclerosis. Comparison of these findings with differentially expressed proteins in human vessels with CVD enabled shortlisting of six commonly dysregulated proteins. Among them, lysine-specific demethylase 5D (KDM5D) exhibited pronounced overexpression accompanied by a reduction in the protein levels of its substrate, the trimethylated lysine 4 of histone H3 (H3K4me3), in patients with CVD. Functional interference studies applying a KDM5 inhibitor on HUVEC reduced cell proliferation, migration and tube-forming ability in vitro. Interpretation: This high-throughput proteomics strategy identified KDM5 histone demethylases being potentially involved in CVD, possibly by affecting H3K4 methylation. Fund: [SysVasc, HEALTH-2013 603288], [ERA-CVD PROACT: ANR-17-ECVD-0006, 01KL1805], [FRM, DEQ20170336759]. © 2019

Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease. Herein, we describe a comprehensive analysis of PFN1 silencing via shRNA, in vitro (by employing T24M cells) and in vivo [(with T24M xenografts in non-obese diabetic severe combined immunodeficient mice (NOD/SCID) mice]. A combination of phenotypic and molecular assays, including migration, proliferation, adhesion assays, flow cytometry and total mRNA sequencing, as well as immunohistochemistry for investigation of selected findings in human specimens were applied. A decrease in BC cell adhesion and tumor growth in vivo following PFN downregulation are observed, likely associated with the concomitant downregulation of Fibronectin receptor, Endothelin-1, and Actin polymerization. A decrease in the levels of multiple key members of the non-canonical Wnt/Ca2+ signaling pathway is also detected following PFN1 suppression, providing the groundwork for future studies, addressing the specific role of PFN1 in Ca2+ signaling, particularly in the muscle invasive disease.

Numerous studies have shown the presence of high levels of growth factors during the process of healing. Growth factors act by binding to the cell surface receptors and contribute to the subsequent activation of signal transduction mechanisms. Wound healing requires a complex of biological and molecular events that includes attraction and proliferation of different type of cells to the wound site, differentiation and angiogenesis. More specifically, migration of various cell types, such as endothelial cells and their precursors, mesenchymal stem/stromal cells (MSCs) or skin fibroblasts (DFs) plays an important role in the healing process. In recent years, the application of platelet rich plasma (PRP) to surgical wounds and skin ulcerations is becoming more frequent, as it is believed to accelerate the healing process. The local enrichment of growth factors at the wound after PRP application causes a stimulation of tissue regeneration. Herein, we studied: (i) the effect of autologous PRP in skin ulcers of patients of different aetiology, (ii) the proteomic profile of PRP, (iii) the migration potential of amniotic fluid MSCs and DFs in the presence of PRP extract in vitro, (iv) the use of the PRP extract as a substitute for serum in cultivating AF-MSCs. Considering its easy access, PRP may provide a valuable tool in multiple therapeutic approaches.

The potential use of patient-specific induced pluripotent stem cells (hiPSCs) in the study and treatment of hematological diseases requires the setup of efficient and safe protocols for hiPSC generation. We aimed to adopt a reprogramming method for large-scale production of integration-free patient-specific hiPSC-lines in our stem cell processing laboratory, which supports a pediatric hematopoietic stem cell transplant unit located at a tertiary care children's hospital. We describe our 5-year experience in generation of hiPSC-lines from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) using synthetic mRNAs encoding reprogramming factors. We generated hiPSC-lines from pediatric patients with β-Thalassemia, Sickle Cell Anemia, Blackfan-Diamond Anemia, Severe Aplastic Anemia, DOCK8 Immunodeficiency and 1 healthy control. After optimization of the reprogramming procedure, average reprogramming efficiency of BM-MSCs was 0.29% (range 0.25–0.4). The complete reprogramming process lasted 14–16 days. Three to five hiPSC-colonies per sample were selected, expanded to 5 culture passages and then frozen. The whole procedure took an average time of 1.8 months (range 1.6–2.2). The hiPSC-lines expressed embryonic stem cell markers and exhibited pluripotency. This mRNA reprogramming method can be applicable in a hematopoietic stem cell culture lab setting and would be useful for the clinical translation of patient-specific hiPSCs.

Aortic arch pathologies such as acute aortic dissection and aneurysmal disease represent surgical challenges. Various emerging techniques and surgical prostheses have expanded the therapeutic armamentarium over the last years with one principal objective; to simplify the operation and reduce the surgical time. Besides the classic elephant trunk which has been regarded as an evolutionary leap in the treatment of extensive thoracic disease, other novel surgical approaches such as the frozen elephant trunk, the thoracic endovascular aortic repair (TEVAR) and the hybrid open branched stent grafts have been introduced. This brief review aims to evaluate the surgical alternatives used in the management of complex aortic arch and proximal descending aorta pathologies with particular consideration given to the contemporary approaches which endorse single stage operation.

""Polyamine oxidases (PAOs) are FAD-dependent enzymes involved in polyamine catabolism. In Arabidopsis thaliana, five PAOs (AtPAO1-5) are present with cytosolic or peroxisomal localization. Here, we present a detailed study of the expression pattern of AtPAO1, AtPAO2, AtPAO3 and AtPAO5 during seedling and flower growth and development through analysis of promoter activity in AtPAO::β-glucuronidase (GUS) transgenic Arabidopsis plants. The results reveal distinct expression patterns for each studied member of the AtPAO gene family. AtPAO1 is mostly expressed in the transition region between the meristematic and the elongation zone of roots and anther tapetum, AtPAO2 in the quiescent center, columella initials and pollen, AtPAO3 in columella, guard cells and pollen, and AtPAO5 in the vascular system of roots and hypocotyls. Furthermore, treatment with the plant hormone abscisic acid induced expression of AtPAO1 in root tip and AtPAO2 in guard cells. These data suggest distinct physiological role(s) for each member of the AtPAO gene family. . ""

Spermidine (Spd) treatment inhibited root cell elongation, promoted deposition of phenolics in cell walls of rhizodermis, xylem elements, and vascular parenchyma, and resulted in a higher number of cells resting in G1 and G2 phases in the maize (Zea mays) primary root apex. Furthermore, Spd treatment induced nuclear condensation and DNA fragmentation as well as precocious differentiation and cell death in both early metaxylem and late metaxylem precursors. Treatment with either N-prenylagmatine, a selective inhibitor of polyamine oxidase (PAO) enzyme activity, or N,N 1-dimethylthiourea, a hydrogen peroxide (H2O2) scavenger, reverted Spd-induced autofluorescence intensification, DNA fragmentation, inhibition of root cell elongation, as well as reduction of percentage of nuclei in S phase. Transmission electron microscopy showed that N-prenylagmatine inhibited the differentiation of the secondary wall of early and late metaxylem elements, and xylem parenchymal cells. Moreover, although root growth and xylem differentiation in antisense PAO tobacco (Nicotiana tabacum) plants were unaltered, overexpression of maize PAO (S-ZmPAO) as well as down-regulation of the gene encoding S-adenosyl-l-methionine decarboxylase via RNAi in tobacco plants promoted vascular cell differentiation and induced programmed cell death in root cap cells. Furthermore, following Spd treatment in maize and ZmPAO overexpression in tobacco, the in vivo H2O2 production was enhanced in xylem tissues. Overall, our results suggest that, after Spd supply or PAO overexpression, H2O2 derived from polyamine catabolism behaves as a signal for secondary wall deposition and for induction of developmental programmed cell death.

This report describes an approach for the treatment of high-risk native mitral valve stenosis. It incorporates the deployment of a transcatheter valve in the mitral position under full endoscopic vision, combined with endoscopic mitral repair techniques that secure valve positioning and reduce the risk of paravalvular leak. This approach could be used as a rescue procedure in centres with experience in transcatheter and endoscopic valve techniques.

The intra-/intercellular homeostasis of reactive oxygen species (ROS), and especially of superoxides (O

The intra-/intercellular homeostasis of reactive oxygen species (ROS), and especially of superoxides (O2.-) and hydrogen peroxide (O2.-) participate in signalling cascades which dictate developmental processes and reactions to biotic/abiotic stresses. Polyamine oxidases terminally oxidize/back convert polyamines generating H2O2. Recently, an NADPH-oxidase/Polyamine oxidase feedback loop was identified to control oxidative burst under salinity. Thus, the real-time localization/monitoring of ROS in specific cells, such as the guard cells, can be of great interest. Here we present a detailed description of the real-time in vivo monitoring of ROS in the guard cells using H2O2- and O2.- specific fluorescing probes, which can be used for studying ROS accumulation generated from any source, including the amine oxidases-dependent pathway, during development and stress.

OBJECTIVES Our goal was to report the clinical and echocardiographic outcomes of endoscopic port access surgery for isolated active and convalescent atrioventricular valve endocarditis (AVVE). METHODS Our current surgical team performed endoscopic port access surgery in 66 consecutive patients with isolated AVVE (mean age, 65.5 ± 12.7 years, 37.9% women, mean EuroSCORE II 31.2 ± 24.9%, 45.5% prosthetic AVVE, Staphylococcus aureus 22.2%), between 1 May 2004 and 31 July 2015. Isolated mitral valve endocarditis was present in 53 (80.4%) patients, including 11 (16.7%) with periannular abscesses. RESULTS Procedures performed included mitral valve repair (n = 15, 22.7%) and left ventricular septal myomectomy (n = 1, 1.5%). Reasons for sternotomy conversion (n = 6, 9.1%) included lung adhesions (n = 3, 4.5%). The mean cardiopulmonary bypass and ischaemic times were 167.2 ±48.7 and 112.6 ± 33.3 min, respectively. In-hospital morbidities included revision for bleeding (n = 6, 9.1%). The 30-day survival rate was 87.9%. Causes of in-hospital deaths (n = 12) included low cardiac output syndrome (n = 3, 4.5%). Age, critical preoperative status and EuroSCORE II score predicted deaths individually at the 5% level of significance. The Kaplan-Meier analyses (mean 63.2 ± 42.5 months) for survival and freedom from AVVE reintervention at 10 years were 69.4% and 98.4%, respectively. Of the mid-term survivors (n = 50, 93.9% complete), 94.0% (n = 47) classified as New York Heart Association (NYHA) II or less with no mitral valve regurgitation greater than Grade I. CONCLUSIONS Complex atrioventricular valve surgery in the context of AVVE can be endoscopically performed in experienced centres and should not deter surgeons from offering patients with AVVE the potential benefits of minimally invasive cardiac surgery.

The concept of Regenerative Medicine combined with Cell based Therapy and Tissue Engineering represents the fourth pillar of healthcare and provides a promising approach for the treatment of serious diseases. Recently, cell based therapies are focused on the use of mesenchymal stem/stromal cells (MSCs). Human MSCs, that represent a mesoderm derived population of progenitors, are easily expanded in culture. They are capable to differentiate into osteoblasts, chondrocytes, and adipocytes and exhibit the potential to repair or regenerate damaged tissues. The best characterized source of human MSCs to date is the bone marrow; recently, fetal sources, such as amniotic fluid, umbilical cord, amniotic membranes, or placenta, have also attracted increased attention. Thus, MSCs may represent a valuable tool for tissue repair and cell therapeutic applications. To this end, the main focus of this review is to summarize and evaluate the key characteristics, the sources, and the potential use of MSCs in therapeutic approaches and modalities.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the anterolateral or the inferior wall served as a better location for the 2nd arterial graft in a 3-system coronary artery bypass grafting procedure. In total, more than 1800 papers were found, of which 6 represented the best evidence to answer the clinical question. All papers demonstrated equivalent early postoperative mortality and morbidity. The 3 largest studies comparing bilateral internal thoracic arteries showed no difference in perioperative mortality and morbidity regardless of whether the 2nd internal thoracic artery was used to graft the left or right system. One of these studies, however, showed significant survival benefit for the left-sided group at 8 years, whereas another study showed a reduced patency of right internal thoracic arteries when grafted to the right coronary artery and when used in situ. One study compared radial grafts to the right- and left-sided targets and showed no difference in long-term patency. Another study also reported on the angiographic patency of right internal thoracic arteries. The authors noted a non-significant increase in graft failure when non-left anterior descending arteries were grafted but no difference between circumflex or posterior descending arteries. All studies demonstrated similar or better mid- and long-term outcomes and patency rates when using the 2nd arterial graft to revascularize left-sided targets when compared with the right. However, all outcomes were similar when comparing non-left anterior descending left-sided targets with non-right coronary artery right-sided targets. Therefore, the right coronary artery itself should probably be avoided as the 2nd arterial target.

Circulating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells. After validating candidate miRNAs by q-RT-PCR, we selected miR-193a-3p for further investigation. The miR-193a-3p mimic reduced cord blood ECFC-derived cell proliferation, migration and vascular tubule formation, while the miR-193a-3p inhibitor significantly enhanced these parameters in peripheral blood ECFC-derived cells. Using in silico miRNA target database analyses combined with proteome arrays and luciferase reporter assays of miR-193a-3p mimic treated cord blood ECFC-derived cells, we identified 2 novel miR-193a-3p targets, the high mobility group box-1 (HMGB1) and the hypoxia upregulated-1 (HYOU1) gene products. HMGB1 silencing in cord blood ECFC-derived cells confirmed its role in regulating vascular function. Thus, we show, for the first time, that miR-193a-3p negatively regulates human ECFC vasculo/angiogenesis and propose that antagonising miR-193a-3p in less proliferative and less angiogenic ECFC-derived cells will enhance their vasculo/angiogenic function.

Polyamines (PAs) and hydrogen peroxide (H2O2), the product of PA oxidation by polyamine oxidase (PAO), are potential players affecting plant growth, development and responses to abiotic/biotic stresses. Genetically modified Nicotiana tabacum plants with altered PA/H2O2 homeostasis due to over/underexpression of the ZmPAO gene (S-ZmPAO/AS-ZmPAO, respectively) were assessed under heat stress (HS). Underexpression of ZmPAO correlates with increased thermotolerance of the photosynthetic machinery and improved biomass accumulation, accompanied by enhanced levels of the enzymatic and non-enzymatic antioxidants, whereas ZmPAO overexpressors exhibit significant impairment of thermotolerance. These data provide important clues on PA catabolism/H2O2/thermotolerance, which merit further exploitation.

Introduction: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Methods: Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). Results: There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction abnormalities (46.7%). The mean length of hospital stay was 26 days. At pre-discharge echocardiography, the conduit mean gradient was 9.3±3.3mmHg and there was either none (n=6), trace (n=6) or mild aortic insufficiency (n=1). There was no incidence of mid-term death, prosthesis-related complications or recurrent endocarditis. Conclusions: Xenograft bioconduits may be safe and effective for aortic valve and root replacement for complex PVE with aortic root abscess. Although excess early mortality reflects the complexity of the patient population, there was good valve hemodynamics, with no incidence of recurrent endocarditis or prosthesis failure in the mid-term. Our data support the continued use and evaluation of this biological prosthesis in this high-risk patient cohort.

Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells). MiR-26a was identified in high expression levels in AL cells indicating a critical role in the process of adipogenesis. Overexpression of miR-26a in AF-MSCs led to significant induction of their adipogenic differentiation properties that were altered after miR-26a inhibition. We have demonstrated that miR-26a regulates adipogenesis through direct inhibition of PTEN, which in turn promotes activation of Akt pathway. Also, miR-26a modulates cell cycle during adipogenesis by interacting with Cyclin E1 and CDK6. These results point to the regulatory role of miR-26a and its target genes PTEN, Cyclin E1, and CDK6 in adipogenic differentiation of AF-MSCs, providing a basis for understanding the mechanisms of fat cell development and obesity.

Circulating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells. After validating candidate miRNAs by q-RT-PCR, we selected miR-193a-3p for further investigation. The miR-193a-3p mimic reduced cord blood ECFC-derived cell proliferation, migration and vascular tubule formation, while the miR-193a-3p inhibitor significantly enhanced these parameters in peripheral blood ECFC-derived cells. Using in silico miRNA target database analyses combined with proteome arrays and luciferase reporter assays of miR-193a-3p mimic treated cord blood ECFC-derived cells, we identified 2 novel miR-193a-3p targets, the high mobility group box-1 (HMGB1) and the hypoxia upregulated-1 (HYOU1) gene products. HMGB1 silencing in cord blood ECFC-derived cells confirmed its role in regulating vascular function. Thus, we show, for the first time, that miR-193a-3p negatively regulates human ECFC vasculo/angiogenesis and propose that antagonising miR-193a-3p in less proliferative and less angiogenic ECFC-derived cells will enhance their vasculo/angiogenic function. © The Author(s) 2017.

Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro, but not in vivo. Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target. © Latosinska et al.

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of `cell-assisted lipotransfer'. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell-assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell-assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell-assisted lipotransfer.

Polyamine (PA) homeostasis is associated with plant development, growth and responses to biotic/abiotic stresses. Apoplastic PA oxidase (PAO) catalyzes the oxidation of PAs contributing to cellular homeostasis of reactive oxygen species (ROS) and PAs. In tobacco, PAs decrease with plant age, while apoplastic PAO activity increases. Our previous results with young transgenic tobacco plants with enhanced/reduced apoplastic PAO activity (S-ZmPAO/AS-ZmPAO, respectively) established the importance of apoplastic PAO in controlling tolerance to short-term salt stress. However, it remains unclear if the apoplastic PAO pathway is important for salt tolerance at later stages of plant development. In this work, we examined whether apoplastic PAO controls also plant development and tolerance of adult plants during long-term salt stress. The AS-ZmPAO plants contained higher Ca2+ during salt stress, showing also reduced chlorophyll content index (CCI), leaf area and biomass but taller phenotype compared to the wild-type plants during salt. On the contrary, the S-ZmPAO had more leaves with slightly greater size compared to the AS-ZmPAO and higher antioxidant genes/enzyme activities. Accumulation of proline in the roots was evident at prolonged stress and correlated negatively with PAO deregulation as did the transcripts of genes mediating ethylene biosynthesis. In contrast to the strong effect of apoplastic PAO to salt tolerance in young plants described previously, the effect it exerts at later stages of development is rather moderate. However, the different phenotypes observed in plants deregulating PAO reinforce the view that apoplastic PAO exerts multifaceted roles on plant growth and stress responses. Our data suggest that deregulation of the apoplastic PAO can be further examined as a potential approach to breed plants with enhanced/reduced tolerance to abiotic stress with minimal associated trade-offs. © 2017 Elsevier GmbH

Polyamines (PAs) and hydrogen peroxide (H2O2), the product of PA oxidation by polyamine oxidase (PAO), are potential players affecting plant growth, development and responses to abiotic/biotic stresses. Genetically modified Nicotiana tabacum plants with altered PA/H2O2 homeostasis due to over/underexpression of the ZmPAO gene (S-ZmPAO/AS-ZmPAO, respectively) were assessed under heat stress (HS). Underexpression of ZmPAO correlates with increased thermotolerance of the photosynthetic machinery and improved biomass accumulation, accompanied by enhanced levels of the enzymatic and non-enzymatic antioxidants, whereas ZmPAO overexpressors exhibit significant impairment of thermotolerance. These data provide important clues on PA catabolism/H2O2/thermotolerance, which merit further exploitation. © 2017

The concept of Regenerative Medicine combined with Cell based Therapy and Tissue Engineering represents the fourth pillar of healthcare and provides a promising approach for the treatment of serious diseases. Recently, cell based therapies are focused on the use of mesenchymal stem/stromal cells (MSCs). Human MSCs, that represent a mesoderm derived population of progenitors, are easily expanded in culture. They are capable to differentiate into osteoblasts, chondrocytes, and adipocytes and exhibit the potential to repair or regenerate damaged tissues. The best characterized source of human MSCs to date is the bone marrow; recently, fetal sources, such as amniotic fluid, umbilical cord, amniotic membranes, or placenta, have also attracted increased attention. Thus, MSCs may represent a valuable tool for tissue repair and cell therapeutic applications. To this end, the main focus of this review is to summarize and evaluate the key characteristics, the sources, and the potential use of MSCs in therapeutic approaches and modalities. © Copyright 2017, Mary Ann Liebert, Inc. 2017.

Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells). MiR-26a was identified in high expression levels in AL cells indicating a critical role in the process of adipogenesis. Overexpression of miR-26a in AF-MSCs led to significant induction of their adipogenic differentiation properties that were altered after miR-26a inhibition. We have demonstrated that miR-26a regulates adipogenesis through direct inhibition of PTEN, which in turn promotes activation of Akt pathway. Also, miR-26a modulates cell cycle during adipogenesis by interacting with Cyclin E1 and CDK6. These results point to the regulatory role of miR-26a and its target genes PTEN, Cyclin E1, and CDK6 in adipogenic differentiation of AF-MSCs, providing a basis for understanding the mechanisms of fat cell development and obesity.

Lecture given by Professor Kalliopi Roubelakis-Angelakis, University of Crete, Department of Biology, Greece at the Waite Campus, University of Adelaide, 2.12.1996.This lecture is part of the Campus Seminars and Distinguished Lecturer Series, Waite Campus, University of Adelaide, 1991 – 1997. https://figshare.com/projects/Campus_Seminars_and_Distinguished_Lecturer_Series_Waite_Campus_University_of_Adelaide/17756

The hangman motif provides mechanistic insights into the role of pendant proton relays in governing proton-coupled electron transfer (PCET) involved in the hydrogen evolution reaction (HER). We now show improved HER activity of Ni compared with Co hangman porphyrins. Cyclic voltammogram data and simulations, together with computational studies using density functional theory, implicate a shift in electrokinetic zone between Co and Ni hangman porphyrins due to a change in the PCET mechanism. Unlike the Co hangman porphyrin, the Ni hangman porphyrin does not require reduction to the formally metal(0) species before protonation by weak acids in acetonitrile. We conclude that protonation likely occurs at the Ni(I) state followed by reduction, in a stepwise proton transfer-electron transfer pathway. Spectroelectrochemical and computational studies reveal that upon reduction of the Ni(II) compound, the first electron is transferred to a metal-based orbital, whereas the second electron is transferred to a molecular orbital on the porphyrin ring.

Objectives We evaluated whether single-port video-assisted thoracic surgery is feasible without compromising outcomes, and whether the technique could be reproduced by a trainee. Methods In a 6-month period, 37 operations were performed by single-port video-assisted thoracic surgery. Of the 37 patients, 27 (73%) were male and the mean age was 45.1 ± 21 years. Twenty-three (62%) were operated on by consultants and 14 (38%) by trainees. The procedures included 19 (51.3%) operations for treatment of pneumothoraces, 8 (21.6%) metastasectomies, 7 (18.9%) lung biopsies, 2 (5.4%) empyema débridements, and 1 (2.7%) pleuropericardial window. Results Mean operative time was 51.8 ± 14.7 min. Patient-controlled analgesia infusion was used for 1.3 ± 1 days. Three (8.1%) patients needed an operative reintervention, but there was no intensive treatment unit admission or hospital mortality. Mean postoperative hospital stay was 3.3 ± 2.7 days. On follow-up, all patients had a tissue diagnosis and all lung nodules were R0 resections. Patients operated on by consultants and trainees had similar preoperative profiles and postoperative outcomes, except that those operated on by trainees used patient-controlled analgesia significantly longer (1.8 ± 1.48 vs. 1 ± 0.48 days; p = 0.03). Conclusion Single-port video-assisted thoracic surgery can be performed and reproduced well without compromising outcomes. It is considered aesthetically better and may reduce analgesic requirements, but it might not reduce hospital stay.