Valproic acid ameliorates morpho-dysfunctional effects triggered by Ischiatic nerve crush injury-induced by compression model in mice: Nerve regeneration and immune-modulatory pathway.

Peripheral nerve injuries are extremely severe and may lead to permanent disability, despite the regenerative capacity of the peripheral nervous system (PNS). To date, there is no established pharmacological therapy capable of predicting functional recovery and alleviation of trauma-related symptoms such as neuropathic pain, inflammation and weakness, which are the main targets for current therapies. In this work we provide new evidence for a therapeutic use of valproic acid (VPA) upon ischiatic nerve injury.

Epigenetic control of myeloid cells behavior by Histone Deacetylase activity (HDAC) during tissue and organ regeneration in Xenopus laevis.

In the present work we have focused on the Histone Deacetylase (HDAC) control of myeloid cells behavior during Xenopus tail regeneration. Here we show that myeloid differentiation is crucial to modulate the regenerative ability of Xenopus tadpoles in a HDAC activity-dependent fashion. HDAC activity inhibition during the first wave of myeloid differentiation disrupted myeloid cells dynamics in the regenerative bud as well the mRNA expression pattern of myeloid markers, such as LURP, MPOX, Spib and mmp7.

Epigenetic Therapy as a Putative Molecular Target to Modulate B Cell Biology and Behavior in the Context of Immunological Disorders.

Histone Deacetylase- (HDAC-) dependent epigenetic mechanisms have been widely explored in the last decade in different types of malignancies in preclinical studies. This effort led to the discovery and development of a range of new HDAC inhibitors (iHDAC) with different chemical properties and selective abilities. In fact, hematological malignancies were the first ones to have new iHDACs approved for clinical use, such as Vorinostat and Romidepsin for cutaneous T cell lymphoma and panobinostat for multiple myeloma.

The epigenome as a putative target for skin repair: the HDAC inhibitor Trichostatin A modulates myeloid progenitor plasticity and behavior and improves wound healing.

Background: The molecular pathways that drive bone marrow myeloid progenitors (BMMP) development are very well understood and include a tight controlled multi-stage gene hierarch. Monocytes are versatile cells that display remarkable plasticity and may give rise to specific subsets of macrophages to proper promote tissue homesostasis upon an injury. However, the epigenetic mechanisms that underlie monocyte differentiation into the pro-inflammatory Ly6C or the repairing Ly6C subsets are yet to be elucidated.

Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation.

Galectin-3 (Gal-3) is a β-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways.

Differential development of oil granulomas induced by pristane injection in galectin-3 deficient mice.

Background: Galectin-3 is known to be a lectin that plays an important role in inflammatory processes, acting as pro-inflammatory mediator in activation and migration of neutrophils and macrophages, as well as in the phagocytic function of these cells. The injection of mineral oils into the peritoneal cavity of mice, such as 2, 6, 10, 14-tetramethylpentadecane (pristane), induce a chronic granulomatous inflammatory reaction which is rich in macrophages, B cells and peritoneal plasma cells known as oil granuloma. In addition, this inflammatory microenvironment provided by oil granulomas is also an important site of plasmacytoma induction, which are dependent on cytokine production and cellular mobilization.