Effects of nutrients, mainly from mediterranean dietary foods, on mesenchymal stem derived cells: growth or differentiation

During the last decade the interest for the mesenchymal cells is growing due to their possible uses in therapies to treat certain degenerative pathologies. Mesenchymal stem cells have been found in the bone marrow and they have been shown to be responsible for bone repair and fat cells production. Mesenchymal stromal cells can be obtained from a wide variety of tissues in addition to bone marrow and can differentiate into many other cell types. The study of cell differentiation and programming provides new models for drug discovery and cell therapy that now overcomes gene therapy. Senescence, cancer development and degenerative diseases depend on mesenchymal cells contribution to tissue homeostasis. On the other hand, diet and life style are included among risk factors, which can contribute to the success of pharmacological treatments. This review focuses on nutrients from Mediterranean diet and supplements, which have been shown to influence mesenchymal stem cells and cells derived from them. Dietary intake of nutrients impairs both in vitro and in vivo observations, this review aims to gather the results about the effects of food compounds on mesenchymal cells from which adipocytes and osteoblasts derive. Amino acids and proteins, carbohydrates, lipids, fatty acids and vegetable secondary metabolites, differently act on mesenchymal cells bearing on modulation of gene expression and controlling the fate of cell lineages. Remarkable, the analysis of literature shows that the main effect of nutrients on mesenchymal cells is the stimulation of transcription factors which address the cells toward proliferation or differentiation. For instance, carbohydrates, simple or complex, and lipids appear to stimulate the PPAR receptors, whereas proteins and amino acids result to act on the mTOR system and they can also stimulate the MyoD-1 transcription factor and cooperating proteins. In conclusion, nutrients can promote cell growth and differentiation of mesenchymal cells

A peptidyl-glucosamine derivative affects IKKα kinase activity in human chondrocytes

Nuclear factor-kappaB (NF-kappaB) transcription factor regulates several cell signaling pathways, such as differentiation and inflammation, which are both altered in osteoarthritis. Inhibitor kappaB kinase (IKK)alpha and IKKbeta are kinases involved in the activation of the NF-kappaB transcription factor. The aim of the present study was to determine the effects of glucosamine (GlcN), which is administered in the treatment of osteoarthritis, and of its 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-beta-D-glucose (NAPA) derivative on IKK kinases and, consequently, on NF-kappaB activation in human chondrocytes. The human chondrosarcoma cell line HTB-94 and human primary chondrocytes were stimulated with tumor necrosis factor (TNF)alpha after pre-treatment with GlcN or NAPA. Gene mRNA expression level was evaluated by real-time PCR. Inhibitor kappaB protein (IkappaB)alpha phosphorylation and p65 nuclear re-localization were analyzed by Western blotting; IKKalpha nuclear re-localization was also investigated by immunocytochemistry and Western blotting. IKK kinase activity was studied by in vitro kinase assay. After TNFalpha stimulation, the mRNA expression level of some of the genes under NF-kappaB control, such as interleukin (IL)-6 and IL-8, increased, while treatment with GlcN and NAPA reverted the effect. We investigated the possibility that GlcN and NAPA inhibit IKK kinase activity and found that NAPA inhibits the IKKalpha kinase activity, whereas GlcN does not. Interestingly, both GlcN and NAPA inhibit IKKalpha nuclear re-localization. Our results demonstrate that glucosamine and its peptidyl derivative can interfere with NF-kappaB signaling pathway by inhibiting IKKalpha activity in human chondrocytes. However, the mechanism of action of the two molecules is not completely overlapping. While NAPA can both specifically inhibit the IKKalpha kinase activity and IKKalpha nuclear re-localization, GlcN only acts on IKKalpha nuclear re-localization

Educación y turismo: una herramienta para la transformación social

Con el objetivo de promover derechos de niños/as y jóvenes en situación de vulnerabilidad, la Fundación Valdocco ha desarrollado en las provincias de Santa Cruz, Chaco, Buenos Aires y la República de Haití, Casas Educativas Terapéuticas y Centros Educativos. El Centro Educativo en sus distintos niveles, ha iniciado sus actividades en 2009 en Comandancia Frías (Impenetrable Chaqueño), siendo una de las carreras de nivel superior la Tecnicatura en Gestión de Turismo Sostenible, que se dicta actualmente también en Isla Maciel, Avellaneda. El propósito es formar profesionales íntegros, capaces de generar un proyecto territorial planificado y ejecutado por ellos, utilizando el turismo sostenible como herramienta de desarrollo. El énfasis está puesto en la participación de la comunidad local, la valorización del patrimonio y el fortalecimiento de la identidad, la concientización y el cuidado del ambiente y la generación de un producto innovador que permita la dinamización de la zona, beneficiando a los residentes, brindando una experiencia significativa para los visitantes y creando una cadena de promoción y comercialización. Para el logro del circuito “Impenetrable, descubrí los secretos del monte chaqueño”34, se trabajó en la valorización del Patrimonio natural y sociocultural, integrando a wichis y criollos, y creando un inventario único en la zona. Además, se creó el alojamiento “Las Chuñas”, que se rige por el uso de buenas prácticas. El circuito “La Isla desde adentro”35 está basado en la revalorización histórica y el relevamiento del patrimonio arquitectónico y cultural, interviniendo en su restauración. Contamos con un paseo guiado y con la creación de un archivo documentado. El logro final será la creación de una tanguería. Nuestro desafío es colaborar con la ruptura del esquema del turismo tradicional como hecho económico, priorizando cuestiones sociales y ambientales.Facultad de Ciencias Económica

Nuevos entramados narrativos: recorridos en la memoria y resignificación patrimonial en territorios de conflicto : El caso de Avellaneda

La experiencia aquí presentada es el resultado del trabajo mancomunado de varias asignaturas de la carrera de Guía Universitario de Turismo (UNDAV), que tienen como núcleo y preocupación común, el estudio y análisis del potencial patrimonial y turístico del área de influencia de la UNDAV (considerando como tal, la zona ribereña al Riachuelo y el GBA Sur-Este), desde una perspectiva de revalorización colectiva y propia de la cultura y la identidad popular. Una primera investigación ha revelado que los entramados narrativos, conformados por distintos lenguajes y acciones significativas, han activado ciertos objetos, bienes y experiencias vinculadas a la historia Avellanedense. Sin embargo, el trabajo de campo realizado ha permitido registrar una multiplicidad de historias, experiencias y espacios que, aún cuando han sido invisibilizados en la narración oficial, tienen una presencia contundente en el territorio.Eje 4: Prácticas socio-comunitarias en la formación y compromiso social de la universidad. Políticas y estrategias de extensión universitaria: reflexiones y debates.Secretaría de Asuntos Académico

Educación y turismo: una herramienta para la transformación social

Con el objetivo de promover derechos de niños/as y jóvenes en situación de vulnerabilidad, la Fundación Valdocco ha desarrollado en las provincias de Santa Cruz, Chaco, Buenos Aires y la República de Haití, Casas Educativas Terapéuticas y Centros Educativos. El Centro Educativo en sus distintos niveles, ha iniciado sus actividades en 2009 en Comandancia Frías (Impenetrable Chaqueño), siendo una de las carreras de nivel superior la Tecnicatura en Gestión de Turismo Sostenible, que se dicta actualmente también en Isla Maciel, Avellaneda. El propósito es formar profesionales íntegros, capaces de generar un proyecto territorial planificado y ejecutado por ellos, utilizando el turismo sostenible como herramienta de desarrollo. El énfasis está puesto en la participación de la comunidad local, la valorización del patrimonio y el fortalecimiento de la identidad, la concientización y el cuidado del ambiente y la generación de un producto innovador que permita la dinamización de la zona, beneficiando a los residentes, brindando una experiencia significativa para los visitantes y creando una cadena de promoción y comercialización. Para el logro del circuito “Impenetrable, descubrí los secretos del monte chaqueño”34, se trabajó en la valorización del Patrimonio natural y sociocultural, integrando a wichis y criollos, y creando un inventario único en la zona. Además, se creó el alojamiento “Las Chuñas”, que se rige por el uso de buenas prácticas. El circuito “La Isla desde adentro”35 está basado en la revalorización histórica y el relevamiento del patrimonio arquitectónico y cultural, interviniendo en su restauración. Contamos con un paseo guiado y con la creación de un archivo documentado. El logro final será la creación de una tanguería. Nuestro desafío es colaborar con la ruptura del esquema del turismo tradicional como hecho económico, priorizando cuestiones sociales y ambientales.Facultad de Ciencias Económica

The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines

Mammary serine protease inhibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy)L-phenylalanylamido-2-deoxy-β-D-glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation has been determined in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP

The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes

The aim of this study was to determine the effects of glucosamine on matrix metalloprotease (MMP) production, on mitogen-activated protein kinase (MAPK) phosphorylation, and on activator protein (AP)-1 transcription factor activation in human chondrocytes. The human immortalized cell line lbpva55 and healthy human chondrocytes (obtained from healthy donors) were subjected to challenge with 10 ng/ml IL-1β after pretreatment with 2.5 or 10 mmol/l glucosamine. MMP mRNA expression levels were evaluated using quantitative real-time PCR, and MMP protein production levels were evaluated in the culture supernatant using ELISA. MAPK phosphorylation was evaluated using Western blotting. AP-1 transcription factor activation was evaluated by measuring AP-1 DNA-binding activity. After IL-1β stimulation, levels of MMP-1, MMP-3 and MMP-13 production were markedly increased. Treatment with 2.5 and 10 mmol/l glucosamine reduced expression of these metalloproteases. MMP expression is regulated by transcription factors such as the AP-1 complex, which is activated by phosphorylated MAPKs. IL-1β stimulated phosphorylation of c-jun amino-terminal kinase, p38 MAPK and extracellular signal-regulated kinase-1/2. Glucosamine inhibited c-jun amino-terminal kinase and p38 phosphorylation, and consequently c-jun binding activity. These findings demonstrate, for the first time, that glucosamine inhibits IL-1β-stimulated MMP production in human chondrocytes by affecting MAPK phosphorylation

In vitro antiviral and anti-inflammatory activities of N-Acetylglucosamine: development of an alternative and safe approach to fight viral respiratory infections

Viral respiratory tract infections (RTIs) are responsible for significant morbidity and mortality worldwide. A prominent feature of severe respiratory infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is the cytokine release syndrome. Therefore, there is an urgent need to develop different approaches both against viral replication and against the consequent inflammation. N-acetylglucosamine (GlcNAc), a glucosamine (GlcN) derivative, has been developed as an immunomodulatory and anti-inflammatory inexpensive and non-toxic drug for non-communicable disease treatment and/or prevention. Recent studies have suggested that GlcN, due to its anti-inflammatory activity, could be potentially useful for the control of respiratory virus infections. Our present study aimed to evaluate in two different immortalized cell lines whether GlcNAc could inhibit or reduce both viral infectivity and the inflammatory response to viral infection. Two different viruses, frequent cause of upper and lower respiratory tract infections, were used: the H1N1 Influenza A virus (IAV) (as model of enveloped RNA virus) and the Human adenovirus type 2 (Adv) (as model of naked DNA virus). Two forms of GlcNAc have been considered, bulk GlcNAc and GlcNAc in nanoform to overcome the possible pharmacokinetic limitations of GlcNAc. Our study suggests that GlcNAc restricts IAV replication but not Adv infection, whereas nano-GlcNAc inhibits both viruses. Moreover, GlcNAc and mainly its nanoformulation were able to reduce the pro-inflammatory cytokine secretion stimulated by viral infection. The correlation between inflammatory and infection inhibition is discussed

Hyaluronic acid reduces bacterial fouling and promotes fibroblasts’ adhesion onto chitosan 2D-wound dressings

Wound healing is a dynamic process that can be seriously delayed by many factors including infectious complications. The development of dressings with intrinsic wound healing activity and/or releasing bioactive compounds may help with addressing such an issue. In this study, hyaluronic acid (HA) at different percentages (1–35%) was used to modify chitosan (CS) biological and physico-chemical properties in order to obtain 2D-matrices able to promote healing and protect from infection. HA incorporation in the CS matrix decreased film transparency and homogeneity, but improved film water uptake and surface wettability. The water vapor transmission rate (WVTR) increased up to a 5% HA content, where it reached the highest value (672 g/m2 day), and decreased for higher HA contents. At all of the tested HA concentrations, HA affected mechanical properties providing matrices more flexible than pure CS with benefit for wound care. Pure CS films permitted S. epidermidis adhesion and biofilm formation. That was not true for CS/HA matrices, where HA at concentrations equal to or greater than 5% was able to avoid S. epidermidis adhesion. Fibroblasts adhesion also took benefit from the HA presence in the film, especially at 5% content, where the best adhesion and proliferation was found