- Wound Healing and Treatments
- Corneal Surgery and Treatments
- Mesenchymal stem cell research
- Periodontal Regeneration and Treatments
- Cellular Mechanics and Interactions
- TGF-β signaling in diseases
- Natural product bioactivities and synthesis
- Tissue Engineering and Regenerative Medicine
- Nuclear Structure and Function
- Renal and related cancers
- Kruppel-like factors research
- Fungal Biology and Applications
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- Ocular Surface and Contact Lens
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Silk-based biomaterials and applications
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- Cell Image Analysis Techniques
- Pluripotent Stem Cells Research
- NF-κB Signaling Pathways
Instituto Murciano de Investigación Biosanitaria
2017-2024
Hospital Universitario Virgen de la Arrixaca
2011-2022
Universidad Católica San Antonio de Murcia
2020
Biomedical Research Institute
2018
The Honourable Society of Lincoln's Inn
2000-2004
Cancer Research UK
2002-2004
GlaxoSmithKline (United Kingdom)
2002
GlaxoSmithKline (United States)
2002
Ninewells Hospital
2001
University of Dundee
2001
Small molecule inhibitors have proven extremely useful for investigating signal transduction pathways and the potential development into therapeutics inhibiting whose activities contribute to human diseases. Transforming growth factor β (TGF-β) is a member of large family pleiotropic cytokines that are involved in many biological processes, including control, differentiation, migration, cell survival, adhesion, specification developmental fate, both normal diseased states. TGF-β superfamily...
Smad4 plays a pivotal role in all transforming growth factor beta (TGF-beta) signaling pathways. Here we describe six widely expressed alternatively spliced variants of human with deletions different exons the linker, region that separates two well-conserved MH1 and MH2 domains. All these form complexes activated Smad2 Smad3 are incorporated into DNA-binding transcription Fast-1, regardless amount linker they contain. However, sequences encoded by 5 to 7 essential for transcriptional...
Wound healing is a biological process directed to the restoration of tissue that has suffered an injury. An important phase wound generation basal epithelium able wholly replace epidermis wound. A broad range products derived from fibroin and sericin Bombyx mori silk are used stimulate healing. However, so far molecular mechanism underlying this phenomenon not been elucidated. The aim work was determine basis properties proteins using cell model. For purpose, we assayed in scratch assay...
Transforming growth factor β (TGF-β) signalling leads to phosphorylation and activation of receptor-regulated Smad2 Smad3, which form complexes with Smad4 accumulate in the nucleus. The Smads, however, do not seem reside statically cytoplasm absence or nucleus upon TGF-β stimulation, but have been suggested shuttle continuously between these cellular compartments both presence TGF-β. Here we investigate this nucleocytoplasmic shuttling detail living cells using fusions enhanced GFP. We first...
ABSTRACT Large‐surface or deep wounds often become senescent in the inflammatory proliferation stages and cannot progress to reepithelialization. This failure makes intervention necessary provide final sealing epithelial layer. The best current treatment is autologous skin graft, although there are other choices such as allogenic substitutes synthetic dressings. Amniotic membrane (AM) a tissue of interest biological dressing due its properties immunologic characteristics. It has low...
Human amniotic epithelial cells (hAECs) have been the object of intense research due to their potential therapeutic use. In this paper, we present molecular evidence a bona fide mesenchymal transition (EMT) undergone by hAECs. Amniotic membrane (AM)-derived hAECs showed presence typical markers such as E-cadherin and cytokeratins. in culture, however, underwent morphological changes acquiring shape. Epithelial cell were lost markers, vimentin α-SMA, appeared. Several genes associated with...
Abstract Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) overexpression of fascin1, a key protein in actin bundling that plays causative role tumor invasion overexpressed different cancer types with poor prognosis. In silico screening 9591 compounds, including 2037 approved the Food Drug Administration (FDA), was performed, selected...
Background: Fascin1 is the key actin-bundling protein involved in cancer invasion and metastasis whose expression associated with bad prognosis tumor from different origins. Methods: In present study, virtual screening (VS) was performed for search of inhibitors RAL, an FDA-approved inhibitor human immunodeficiency virus-1 (HIV-1) integrase, identified as a potential inhibitor. Biophysical techniques including nuclear magnetic resonance (NMR) differential scanning fluorimetry (DSF) were...
Smad4 is an essential signal transducer of the transforming growth factor β (TGF-β) signalling pathway and has been identified as a tumour suppressor, being mutated in approx. 50% pancreatic cancers 15% colorectal cancers. Two missense mutations C-terminal domain Smad4, D351H (Asp351→His) D537Y (Asp537→Tyr), have described recently human cancer cell lines CACO-2 SW948 respectively [Woodford-Richens, Rowan, Gorman, Halford, Bicknell, Wasan, Roylance, Bodmer Tomlinson (2001) Proc. Natl. Acad....
Defects in wound closure can be related to the failure of keratinocytes re-epithelize. Potential mechanisms driving this impairment comprise unbalanced cytokine signaling, including Transforming Growth Factor-β (TFG-β). Although etiologies chronic development are known, relevant molecular events poorly understood. This lack insight is a consequence ethical issues, which limit available evidence humans. In work, we have used an vitro model validated for study epidermal physiology and...
Background Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary provide final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation traumatic wounds. Methods and Findings To better understand this phenomenon, used keratinocytes investigate effect of AM on chronic Using keratinocytes, saw treatment able exert an...
In normal epithelial cells, transforming growth factor-β (TGF-β) typically causes arrest in the G<sub>1</sub> phase of cell cycle and may eventually lead to apoptosis. However, transformed cells lose these inhibitory responses often instead show an increase malignant character following TGF-β treatment. canine kidney-derived line, MDCK, synergism between activation Raf/MAPK pathway resulting autocrine production triggers transition from a mesenchymal phenotype. During this process, become...
Keratinocyte migration is a mandatory aspect of wound healing. We have previously shown that amniotic membrane (AM) applied to chronic wounds assists healing through process resulting in the overexpression c-Jun at wound's leading edge. also demonstrated AM modifies genetic programme induced by transforming growth factor-ß (TGF-ß) wounds. Here we used scratch assay mink lung epithelial cells (Mv1Lu) and spontaneously immortalized human keratinocyte cell line (HaCaT) examine influence...
The bacterium Myxococcus xanthus responds to blue light by producing carotenoids. It also starvation conditions developing fruiting bodies, where the cells differentiate into myxospores. Each response entails transcriptional activation of a separate set genes. However, single gene, carD, is required for both light- and starvation-inducible Gene carD has now been sequenced. Its predicted amino acid sequence includes four repeats DNA-binding domain present in mammalian high mobility group I(Y)...
The Gram-negative bacterium Myxococcus xanthus responds to blue light by producing carotenoid pigments (Car+ phenotype). Genes for synthesis lie at two unlinked chromosomal sites, the carC and carBA operon, but are integrated in a single "light regulon" action of common trans-acting regulatory elements. Three known genes grouped together (light-inducible) carQRS operon. By screening Car phenotype large collection transposon-induced mutants, we have identified new car locus that has been...
During wound healing, the migration of keratinocytes onto newly restored extracellular matrix aims to reestablish continuity epidermis. The application amniotic membrane (AM) chronic, deep traumatic, non-healing wounds has proven successful at stimulating re-epithelialization. When applied on epithelial cell cultures, AM activates signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal (JNK1/2), with overexpression phosphorylation along edge. effect cells was investigated by studying...
The density gradient centrifugation method was originally designed for the isolation of mononuclear peripheral blood cells and rapidly adapted to fractionate bone marrow (BM) cells. This involves use solutions with low viscosity osmotic pressure that allows erythrocytes more mature gravitate bottom at a fraction superior 1.080 g/dL; (MNCs) held in plasma-solution interphase between 1.053 1.073 plasma, dilution medium anticoagulant occupy less than 1.050 g/dL fat float due their very density....