Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

Diffuse systemic sclerosis (SSc) is a fatal autoimmune disease characterized by an excessive ECM deposition inducing a loss of function of skin and internal organs. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. The purpose of this paper is to gather new findings in apoptosis related to SSc, to highlight relations between apoptosis and fibrosis, and to identify new therapeutic targets

Ageing of reverse osmosis membranes under gamma irradiation

Reverse osmosis (RO) shows a real growth among the water and wastewater treatment processes available (evaporation, ions exchange, electrodialysis) since forty years. RO has become the most used processes for desalination of seawater or saline water. Following Fukushima-Daiichi accident, RO has been chosen as the final treatment of the seawater used to cool the damaged nuclear reactors. Only very few studies and data has been published about RO applied to radioactive wastewater. Currently RO membranes are made of polymers that are sensitive to irradiation and could be strongly damaged due to these ionizing radiations. Data about the ageing of the membranes under these operating conditions are very difficult to obtain even if RO seems to be efficient in the process used in Fukushima. Please click Additional Files below to see the full abstract

Anticancer properties of chitosan on human melanoma are cell line dependent

Purpose: Chitosan, a natural macromolecule, is widely used in medical and pharmaceutical fields because of its distinctive properties such as bactericide, fungicide and above all its antitumor effects. Although its antitumor activity against different types of cancer had been previously described, its mechanism of action was not fully understood. Materials and methods: Coating of chitosan has been used in cell cultures with A375, SKMEL28, and RPMI7951 cell lines. Adherence, proliferation and apoptosis were investigated. Results: Our results revealed that whereas chitosan decreased adhesion of primary melanoma A375 cell line and decreased proliferation of primary melanoma SKMEL28 cell line, it had potent pro-apoptotic effects against RPMI7951, a metastatic melanoma cell line. In these latter cells, inhibition of specific caspases confirmed that apoptosis was effected through the mitochondrial pathway and Western blot analyses showed that chitosan induced an up regulation of pro-apoptotic molecules such as Bax and a down regulation of anti-apoptotic proteins like Bcl-2 and Bcl-XL. More interestingly, chitosan exposure induced an exposition of a greater number of CD95 receptor at RPMI7951 surface, making them more susceptible to FasL-induced apoptosis. Conclusion: Our results indicate that chitosan could be a promising agent for further evaluations in antitumor treatments targeting melanoma

Shedding of microparticles by myofibroblasts as mediator of cellular cross-talk during normal wound healing

Interactions between cells are a crucial mechanism to correctly heal a wounded tissue. Myofibroblasts have a central role during healing but their means to communicate with other cells is unknown. Microparticles (MP) have demonstrated a potential role as mediators of cellular interactions during various diseases. We have analyzed the production of MP by normal (Wmyo) and pathological (hypertrophic scar, Hmyo) myofibroblasts and human dermal fibroblasts (Fb) when treated with serum or plasma as examples of body fluids. We have shown that the presence of these body fluids induced a very significant increase in MP production by Wmyo while no MP production was denoted for Hmyo and Fb. These effects were at least due to thermally sensitive protein(s) with a molecular mass >30 kDa. Furthermore, the increase in MP production was not linked to an increase in apoptotic Wmyo. MP characterization showed that VEGF and FGF2 were present in MP and that endothelial and (myo)fibroblast cell growth can be stimulated by MP treatment. We postulated that MP production by myofibroblasts could modulate mesenchymal cell growth and angiogenesis during normal healing

«II Taller de Arqueometría»

El 24 y 25 de noviembre de 2014, se realizó el II Taller de Arqueometría organizado por el Instituto Francés de Estudios Andinos y el Ministerio de Cultura del Perú a través del Museo de Sitio de Pachacamac. Este evento se dio con la intención de contribuir a la capacitación de profesionales jóvenes interesados en conocer los múltiples aspectos relacionados con las técnicas, metodologías y alcances de la arqueometría. Hoy, más que nunca, el quehacer del arqueólogo se relaciona con la investig..

Production of a bilayered self-assembled skin substitute using a tissue-engineered acellular dermal matrix

Our bilayered self-assembled skin substitutes (SASS) are skin substitutes showing a structure and functionality very similar to native human skin. These constructs are used, in life-threatening burn wounds, as permanent autologous grafts for the treatment of such affected patients even though their production is exacting. We thus intended to shorten their current production time to improve their clinical applicability. A self-assembled decellularized dermal matrix (DM) was used. It allowed the production of an autologous skin substitute from patient's cells. The characterization of SASS reconstructed using a decellularized dermal matrix (SASS-DM) was performed by histology, immunofluorescence, transmission electron microscopy, and uniaxial tensile analysis. Using the SASS-DM, it was possible to reduce the standard production time from about 8 to 4 and a half weeks. The structure, cell differentiation, and mechanical properties of the new skin substitutes were shown to be similar to the SASS. The decellularization process had no influence on the final microstructure and mechanical properties of the DM. This model, by enabling the production of a skin substitute in a shorter time frame without compromising its intrinsic tissue properties, represents a promising addition to the currently available burn and wound treatments

Electric potential across epidermis and its role during wound healing can be studied by using an in vitro reconstructed human skin

Background : After human epidermis wounding, transepithelial potential (TEP) present in nonlesional epidermis decreases and induces an endogenous direct current epithelial electric field (EEF) that could be implicated in the wound re-epithelialization. Some studies suggest that exogenous electric stimulation of wounds can stimulate healing, although the mechanisms remain to be determined. The Problem : Little is known concerning the exact action of the EEF during healing. The mechanism responsible for TEP and EEF is unknown due to the lack of an in vitro model to study this phenomenon. Basic Science Advances : We carried out studies by using a wound created in a human tissue-engineered skin and determined that TEP undergoes ascending and decreasing phases during the epithelium formation. The in vitro TEP measurements over time in the wound were corroborated with histological changes and with in vivo TEP variations during porcine skin wound healing. The expression of a crucial element implicated in Na+ transport, Na+/K+ ATPase pumps, was also evaluated at the same time points during the re-epithelialization process. The ascending and decreasing TEP values were correlated with changes in the expression of these pumps. The distribution of Na+/K+ ATPase pumps also varied according to epidermal differentiation. Further, inhibition of the pump activity induced a significant decrease of the TEP and of the re-epithelization rate. Clinical Care Relevance : A better comprehension of the role of EEF could have important future medical applications regarding the treatment of chronic wound healing. Conclusion : This study brings a new perspective to understand the formation and restoration of TEP during the cutaneous wound healing process

Improved methods to produce tissue-engineered skin substitutes suitable for the permanent closure of full-thickness skin injuries

There is a clinical need for skin substitutes to replace full-thickness skin loss. Our group has developed a bilayered skin substitute produced from the patient’s own fibroblasts and keratinocytes referred to as Self-Assembled Skin Substitute (SASS). After cell isolation and expansion, the current time required to produce SASS is 45 days. We aimed to optimize the manufacturing process to standardize the production of SASS and to reduce production time. The new approach consisted in seeding keratinocytes on a fibroblast-derived tissue sheet before its detachment from the culture plate. Four days following keratinocyte seeding, the resulting tissue was stacked on two fibroblast-derived tissue sheets and cultured at the air–liquid interface for 10 days. The resulting total production time was 31 days. An alternative method adapted to more contractile fibroblasts was also developed. It consisted in adding a peripheral frame before seeding fibroblasts in the culture plate. SASSs produced by both new methods shared similar histology, contractile behavior in vitro and in vivo evolution after grafting onto mice when compared with SASSs produced by the 45-day standard method. In conclusion, the new approach for the production of high-quality human skin substitutes should allow an earlier autologous grafting for the treatment of severely burned patients

Apoptosis, G1 Phase Stall, and Premature Differentiation Account for Low Chimeric Competence of Human and Rhesus Monkey Naive Pluripotent Stem Cells

After reprogramming to naive pluripotency, human pluripotent stem cells (PSCs) still exhibit very low ability to make interspecies chimeras. Whether this is because they are inherently devoid of the attributes of chimeric competency or because naive PSCs cannot colonize embryos from distant species remains to be elucidated. Here, we have used different types of mouse, human, and rhesus monkey naive PSCs and analyzed their ability to colonize rabbit and cynomolgus monkey embryos. Mouse embryonic stem cells (ESCs) remained mitotically active and efficiently colonized host embryos. In contrast, primate naive PSCs colonized host embryos with much lower efficiency. Unlike mouse ESCs, they slowed DNA replication after dissociation and, after injection into host embryos, they stalled in the G1 phase and differentiated prematurely, regardless of host species. We conclude that human and non-human primate naive PSCs do not efficiently make chimeras because they are inherently unfit to remain mitotically active during colonization