M. Leonor Cancela

M. Leonor Cancela
Universidade do Algarve | UALG · Department of Biomedical Sciences and Medicina

PhD and Agregação /Habilitation

About

416
Publications
35,566
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5,122
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Additional affiliations
September 2012 - August 2015
Universidade do Algarve
Position
  • Head of Department
January 2012 - present
Instituto de Biologia Molecular e Celular
January 2012 - present
Laval University

Publications

Publications (416)
Article
The Molecular Genetics Mobile Lab or “Laboratório itinerante de Genética Molecular” (Lab-it) was funded in 2008 by Leonor Cancela to promote the learning of molecular genetics which had been introduced at that time into high school biology programms. The project aimed to introduce hands-on laboratory activities in molecular genetics to complement t...
Article
Full-text available
CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental condition characterized primarily by seizures and impairment of cognitive and motor skills. Additional phenotypes include microcephaly, dysmorphic facial features, and scoliosis. Mutations in cyclin-dependent kinase-like 5 (CDKL5) gene, encoding a kinase essential for normal brain develop...
Article
The presence of microplastics in the aquatic ecosystem represents a major issue for the environment and human health. The capacity of organic pollutants to adsorb onto microplastic particles raises additional concerns, as it creates a new route for toxic compounds to enter the food web. Current knowledge on the impact of pristine and/or contaminate...
Conference Paper
Full-text available
Preprint
The shaping of bone structures relies on various cell types and signalling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion/stitching until the branchpoint, and that bifu...
Article
Full-text available
Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these...
Article
Full-text available
Doxorubicin is a widely used chemotherapeutic drug known to induce bone loss. The mechanism behind doxorubicin-mediated bone loss is unclear, but oxidative stress has been suggested as a potential cause. Antioxidants that can counteract the toxic effect of doxorubicin on the bone would be helpful for the prevention of secondary osteoporosis. We use...
Chapter
Sixty years after the development of the first piscine cell line, more than 700 cell lines have been established from a wide range of fish species and tissues. The fast provision of in vitro cell systems of fish origin has been stimulated by the growing interest for fish in science and sustained by the ability of cultured fish cells to spontaneousl...
Chapter
In this paper, we propose variants of deep learning methods to segment head and operculum of the zebrafish larvae in microscopy images. In the first approach, we used a three-class model to jointly segment head and operculum area of zebrafish larvae from background. In the second, two-step, approach, we first trained binary segmentation model to se...
Article
Full-text available
Persistent and ubiquitous organic pollutants, such as the polycyclic aromatic hydrocarbon benzo[⍺]pyrene (BaP), represent a major threat to aquatic organisms and human health. Beside some well-documented adverse effects on the development and reproduction of aquatic organisms, BaP was recently shown to affect fish bone formation and skeletal develo...
Poster
Full-text available
The BIOSKEL Lab (CCMAR, UALG) is pleased to announce the 3rd WORKSHOP on Zebrafish tools for the screening of osteogenic compounds that will be held at the CCMAR (Faro, PT) from 8 to 10th of September 2021. This workshop aims to provide both conceptual and experimental know-how on zebrafish screening systems through lectures given by experts in the...
Article
Full-text available
Osteoporosis is an aging-related disease and a worldwide health issue. Current therapeutics have failed to reduce the prevalence of osteoporosis in the human population, thus the discovery of compounds with bone anabolic properties that could be the basis of next generation drugs is a priority. Marine plants contain a wide range of bioactive compou...
Article
Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is responsible for the dephosphorylation and inactivation of ERK, JNK and p38, which are mitogen-activated protein kinases involved in cell proliferation, differentiation and apoptosis, but also in inflammation processes. Given its importance for cellular s...
Article
Full-text available
Holt–Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5—a gene encoding a transcription factor important for heart and skeletal development—are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two i...
Article
Full-text available
Osteopenia and osteoporosis are bone disorders characterized by reduced bone mineral density (BMD), altered bone microarchitecture and increased bone fragility. Because of global aging, their incidence is rapidly increasing worldwide and novel treatments that would be more efficient at preventing disease progression and at reducing the risk of bone...
Article
The MEF2C gene encodes a transcription factor known to play a crucial role in molecular pathways affecting neuronal development. MEF2C mutations were described as a genetic cause of developmental disease (MRD20), and several reports sustain its involvement in dementia-related conditions, such as Alzheimer’s disease and amyotrophic lateral sclerosis...
Article
Iron is fundamental for several biological functions, but when in excess can lead to the development of toxic events. Some tissues and cells are more susceptible than others, but systemic iron levels can be controlled by treating patients with iron-chelating molecules and phlebotomy. An early diagnostic can be decisive to limit the progression of m...
Article
Full-text available
Keutel syndrome (KS) is a rare autosomal recessive genetic disorder that was first identified in the beginning of the 1970s and nearly 30 years later attributed to loss-of-function mutations in the gene coding for the matrix Gla protein (MGP). Patients with KS are usually diagnosed during childhood (early onset of the disease), and the major traits...
Conference Paper
Background/Introduction: Low bone mass density associated disorders, such as osteoporosis, affect millions of people worldwide and result in a massive economic burden for society. Current therapeutics are limited and have issues related to costs, efficacy and long-term use. Although still largely unexplored, marine biodiversity represents a promisi...
Conference Paper
Background/Introduction: Thalidomide is a pharmaceutical compound that became popular during the 1950s-60s as treatment for morning sickness usually prescribed to pregnant woman. However, cases of birth defect involving shortened or absent limbs were detected in babies whose mothers took thalidomide during the first weeks of pregnancy. The use of t...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Presentation
Bone disorders such as osteoporosis and Paget´s disease of bone affect millions of people worldwide and available therapeutics have a limited efficacy and often present undesirable side effects. Furthermore, there is a plethora of rare diseases, such as osteopetrosis or osteogenesis imperfecta, that also present severe skeletal phenotypes and for w...
Article
Iron has a fundamental role in life and in its biochemical reactions but, when in excess, it can promote the formation of free radicals which can lead to cell death. Therefore, managing the levels of iron is essential to regulate the production of oxidative stress related to iron, and ferritins are one of the main protein families involved in this...
Poster
Full-text available
Fish cultured in intensive farming conditions commonly develop severe skeletal deformities that affect both welfare and market value. Among the solutions proposed to improve the skeletal status of aquaculture fish, supplementation of their diet with natural compounds or extracts that stimulate skeletogenesis is increasingly seen as an economically...
Article
T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. TBX5 is a transcription factor important for cardiac development and upper limbs formation and its haploinsufficiency causes Holt-Oram syndrome (HOS). An increase in TBX5 dosage also leads to HOS, suggest...
Article
Full-text available
In the present work, we aimed to explore the potential of two groups of marine invertebrates-sea cucumbers (Echinodermata) and ascidians (Chordata)-as sources of anti-inflammatory, anti-oxidant, and osteogenic compounds with potential to be used as pharmaceuticals and nutraceuticals for the treatment and prevention of chronic diseases. 24 extracts...
Presentation
Metabolic bone disorders such as osteoporosis affect millions of people worldwide and drugs currently available have a limited efficacy and have associated secondary effects. There is a compelling need for new compounds with bone anabolic properties acting through new and original mechanisms of action. In this regard, recent works have identified m...
Article
Aim: To provide novel data on the expression of DUSP4 transcripts in colorectal cancer (CRC) tissues and to explore their potential as biomarkers. Materials & methods: DUSP4 transcripts expression was determined by quantitative real-time PCR in tissues from 28 CRC patients. Their association with clinicopathological factors and survival analysis wa...
Article
Full-text available
Teleosts have the ability to regenerate their caudal fin upon amputation. A highly proliferative mass of undifferentiated cells called blastema forms beneath wound epidermis and differentiates to regenerate all missing parts of the fin. To date, the origin and fate of the blastema is not completely understood. However, current hypotheses suggest th...
Article
Objectives Epidemiological evidence suggests that low vitamin K status is associated with osteoarthritis (OA) development and progression. However, it is not clear if low vitamin K intake is causally linked to OA. To address this gap, we manipulated vitamin K intake in aging mice to test its effect on OA development. Methods Eleven-month old male...
Article
Full-text available
Objective While a role for vitamin K in maintaining joint tissue homeostasis has been proposed based on the presence of vitamin K dependent proteins in cartilage and bone, it is not clear if low vitamin K intake is causally linked to joint tissue degeneration. To address this gap, we manipulated vitamin K status in aging mice to test its effect on...
Article
The last decade has seen an increased interest in the discovery of compounds with bone anabolic activity to treat skeletal disorders such as osteoporosis and increase the well-being of patients. Due to the many technical advantages over classical rodent systems, zebrafish (Danio rerio) has been increasingly used in screening pipelines, in particula...
Article
Full-text available
The data presented in this article is related with the research paper entitled “Evaluation of MGP gene expression in colorectal cancer”, available on Gene journal [1]. From all the transcription factors known to regulate MGP, FGF2 is the most described in colon adenocarcinoma and colon tumor cell lines, where it was shown to: i) contribute for the...
Article
Full-text available
The caudal fin of teleost fish has become an excellent system for investigating the mechanisms of epimorphic regeneration. Upon amputation of the caudal fin, a mass of undifferentiated cells, called blastema, proliferate beneath the wound-epidermis and differentiate into various cell types to faithfully restore the missing fin structures. Here we d...
Article
Many anthropogenic chemicals and plastic debris end up in the aquatic ecosystem worldwide, representing a major concern for the environment and human health. Small teleosts, such as zebrafish (Danio rerio) and Japanese medaka (Oryzias latipes), offer significant advantages over classical animal models and are currently used as first-line organisms...
Poster
Full-text available
The BIOSKEL Lab (CCMAR, UALG) is pleased to announce the second WORKSHOP on Zebrafish tools for screening of therapeutic -relevant molecules affecting tissue mineralization that will be held at the CCMAR (Faro, PT) from 25 to 27th of November 2019. This workshop aims to provide both conceptual and experimental know-how on zebrafish screening syst...
Article
Problem The burden of disease for oncological problems is significant in Portugal. Population-based screenings, such as colorectal cancer screening (CCS) with faecal occult blood tests (FIT) is a priority program to reduce the burden of disease and a cost-effectiveness measure. Description problem Algarve CCS started in 2017,to early detect colore...
Poster
Full-text available
Diabetes has been linked to bone loss and to impaired bone regeneration both in humans and mice (1,2). Recently, it has been demonstrated that fin regeneration is also affected in diabetic zebrafish (3). Vitamin D (VitD) was shown to have an anabolic effect in bone mineralization (4). To test this hypothesis we used a zebrafish transgenic line tg(i...
Poster
Full-text available
Diabetes Mellitus type 1 (DMT 1 has been linked to growth retardation in humans and also in diabetic mice models The severity of this symptom is associated to early onset of the disease seen in Permanent Neonatal Diabetes Mellitus ( or maturity onset diabetes of the young Chondrocyte proliferation and vascular invasion of the epiphyseal growth plat...
Poster
Full-text available
The WHO predicts a decrease in life expectancy for the first time in 200 years because of diabetes mellitus (DM), with death rates expected to rise 25%. Between several health problems diabetes mellitus is also linked to osteopenia and osteoporosis. Mouse model Ins2+/- (akita mouse) also presents a clear decrease in bone mineral density (BMD), simi...
Poster
Full-text available
Diabetes Mellitus (DM) is quickly becoming the principal cause of morbidity and mortality in chronic patients worldwide. Type1 DM patients show osteopenia or osteoporosis. Diabetic mice showed an increase in osteoclast number and expression of osteoclastogenic mediators and a decreased osteoblastic proliferation. Like mouse, rat and frog, zebrafish...
Article
Purpose: Matrix Gla protein (MGP) is a vitamin K-dependent, γ-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcif...
Article
Full-text available
Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expres...
Article
Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the...
Article
The consolidation of meagre (Argyrosomus regius) in aquaculture requires an understanding and optimization of larval rearing and nutritional conditions. The aim of this study was to analyse the effects of an early introduction of inert diets during larval rearing, on growth performance, digestive enzymes activity and development of skeletal anomali...
Article
HFE‐hemochromatosis is a disease characterized by a systemic iron overload phenotype mainly associated with mutations in the HFE protein (HFE) gene. Osteoarthritis (OA) has been reported as one of the most prevalent complications in HFE‐hemochromatosis patients, but the mechanisms associated with its onset and progression remain incompletely unders...
Article
Full-text available
The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a cleare...
Article
Full-text available
Extracts and compounds derived from marine organisms have reportedly shown some osteogenic potential. As such, these bioactives may aid in the treatment of musculoskeletal conditions such as osteoporosis; helping to address inefficacies with current treatment options. In this study, 72 fractions were tested for their in vitro osteogenic activity us...
Data
hFOB proliferation with DMSO dissolved extract set 1. Proliferation of hFOBs at day 4 (a) and 7 (b) calculated via PicoGreen assay. Cells were challenged with DMSO dissolved extracts D-01 to D-14. DMSO was included at 0.1%, giving extract concentrations ranging between 20 and 31.7 μg/ml. Cell proliferation, as a percentage of control, is presented...
Data
hFOB proliferation with DMSO dissolved extract set 3. Proliferation of hFOBs at day 4 (a) and 7 (b) calculated via PicoGreen assay. Cells were challenged with DMSO dissolved extracts D-29 to D-43. DMSO was included at 0.1%, giving extract concentrations ranging between 20 and 31.7 μg/ml. Cell proliferation, as a percentage of control, is presented...
Data
Dataset providing all raw values used to create figures in this manuscript. Datasets are labelled according to the extracts tested, the type of data (i.e. in vitro or in vivo), time-point used and which figure the data relates to. (XLSX)
Data
hFOB proliferation with DMSO dissolved extract set 2. Proliferation of hFOBs at day 4 (a) and 7 (b) calculated via PicoGreen assay. Cells were challenged with DMSO dissolved extracts D-15 to D-28. DMSO was included at 0.1%, giving extract concentrations ranging between 20 and 31.7 μg/ml. Cell proliferation, as a percentage of control, is presented...
Data
hFOB cytotoxicity results for DMSO dissolved extracts. Cytotoxicity results (LDH assay) for hFOBs at day 1. Cells were challenged with DMSO dissolved extracts D-01 to D-14 (a), D-15 to D-28 (b) and D-29 to D-43 (c). DMSO was included at 0.1%, giving extract concentrations ranging between 20 and 31.7 μg/ml. Cell death is presented as mean +/- SD (n...
Data
hFOB proliferation results for ethanol dissolved extract set 1. Proliferation of hFOBs at day 4 (a) and 7 (b) calculated via crystal violet assay. Cells were challenged with ethanol dissolved extracts E-01 to E-13 or control (EtOH). Ethanol was included at a 0.5% concentration, giving extract concentrations of 150 μg/ml. Cell proliferation, as a pe...
Data
hFOB proliferation results for ethanol dissolved extract set 2. Proliferation of hFOBs at day 4 (a) and 7 (b) calculated via crystal violet assay. Cells were challenged with ethanol dissolved extracts E-14 to E-25 or control (EtOH). Ethanol was included at a 0.5% concentration, giving extract concentrations of 150 μg/ml (except for E-19: 20.8 μg/ml...
Data
hFOB cytotoxicity results for ethanol dissolved extracts. Cytotoxicity results (LDH assay) for hFOBs at day 1. Cells were challenged with EtOH dissolved fractions E-01—E13 (a) and E-14—E-25 (b). Ethanol was included at a 0.5% concentration, giving extract concentrations of 150 μg/ml (except for E-19: 20.8 μg/ml and E-22: 86 μg/ml). Cell death is pr...
Article
Full-text available
Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that the...
Data
Table A. Primers sequences for gene expression analysis. Sequences and references of primers used in gene expression analysis by qPCR. Fig A Microarchitecture parameters between WT and Hfe-KO mice (12 months old). a- Bone microarchitecture parameters evaluated were bone volume fraction (BV/TV), bone volume (BV), trabecular thickness (Tb.Th), trabec...
Article
Full-text available
Type 1 diabetes mellitus (T1DM) has been associated to several cartilage and bone alterations including growth retardation, increased fracture risk, and bone loss. To determine the effect of long term diabetes on bone we used adult and aging Ins2 Akita mice that developed T1DM around 3–4 weeks after birth. Both Ins2 Akita and wild‐type (WT) mice we...