Manuel Freire-Garabal

Prof. Manuel Freire-Garabal

Department of Pharmacology, School of Medicine and Dentistry, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

Research Focus & Metrics

Academic Career Length

17Years (2010-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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12 May 2016 in Molecules
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Journal Article
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Silvia NovíoSilvia Novío
Silvia Novío
María Elena CarteaMaría Elena Cartea
María Elena Cartea
Pilar SoengasPilar Soengas
Pilar Soengas
MFManuel Freire-Garabal
Manuel Freire-Garabal
MNMaría Jesús Núñez-Iglesias
María Jesús Núñez-Iglesias
Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

30 October 2019 in Antibiotics
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ARAndrea Rábano-Blanco
Andrea Rábano-Blanco
EDEva María Domínguez-Martís
Eva María Domínguez-Martís
DMDiego Gabriel Mosteiro-Miguéns
Diego Gabriel Mosteiro-Miguéns
MFManuel Freire-Garabal
Manuel Freire-Garabal
Silvia NovíoSilvia Novío
Silvia Novío
Antibiotic resistance is an emerging worldwide concern with serious repercussions in terms of morbi-mortality. Bearing in mind that the inadequate use of antibiotics, by healthcare staff as well as by the general population, is one of its main causes, a multidisciplinary approach is required to try to combat it. The aim of the present study was to determine nursing students’ knowledge and awareness of antibiotic use, resistance and stewardship. A cross-sectional design was used. A total of 578 nursing students from the University of Santiago de Compostela (Spain), ≥18 years old of both sexes were invited to complete the Spanish version of the questionnaire “Knowledge and awareness of the use, resistance and administration of antibiotics” between February and April 2019. Students had a low level of knowledge about antibiotics, 4.1 (CI95% = 3.4–4.8), especially in relation to antibiotic resistance. As the students were aware of this deficiency, the majority affirmed (>90%) that the current curriculum of nursing degree should have more training on antibiotics and infection control. Nursing staff play an important role in the rational use of antibiotics and as teachers of patients, so their training could be key in fighting antibiotic resistance.

Verified
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MNMaría Jesús Núñez-Iglesias
María Jesús Núñez-Iglesias
Silvia NovíoSilvia Novío
Silvia Novío
CGCarlota García
Carlota García
EPElena Pérez-Muñuzuri
Elena Pérez-Muñuzuri
Pilar SoengasPilar Soengas
Pilar Soengas
MFManuel Freire-Garabal
Manuel Freire-Garabal
Glucosinolate-degradation products (GS-degradation products) are believed to be responsible for the anticancer effects of cruciferous vegetables. Furthermore, they could improve the efficacy and reduce side-effects of chemotherapy. The aim of the present study was to determine the cytotoxic effects of GS-degradation products on androgen-insensitive human prostate cancer (AIPC) PC-3 and DU 145 cells and investigate their ability to sensitize such cells to chemotherapeutic drug Docetaxel (DOCE). Cells were cultured under growing concentrations of allyl-isothiocyanate (AITC), sulforaphane (SFN), 4-pentenyl-isothiocyanate (4PI), iberin (IB), indole-3-carbinol (I3C), or phenethyl-isothiocyanate (PEITC) in absence or presence of DOCE. The anti-tumor effects of these compounds were analyzed using the trypan blue exclusion, apoptosis, invasion and RT-qPCR assays and confocal microscopy. We observed that AITC, SFN, IB, and/or PEITC induced a dose- and time-dependent cytotoxic effect on PC-3 and DU 145 cells, which was mediated, at least, by apoptosis and cell cycle arrest. Likewise, we showed that these GS-degradation products sensitized both cell lines to DOCE by synergic mechanisms. Taken together, our results indicate that GS-degradation products can be promising compounds as co-adjuvant therapy in prostate cancer.

26 January 2010 in Acta Odontologica Scandinavica
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MNMaría J. Núñez
María J. Núñez
Silvia NovíoSilvia Novío
Silvia Novío
JBJosé Balboa
José Balboa
JSJuan Manuel Seoane
Juan Manuel Seoane
Juan SuárezJuan Suárez
Juan Suárez
MFManuel Freire-Garabal
Manuel Freire-Garabal
Objective. To investigate the effects of resveratrol, a naturally occurring polyphenol, on the expression of vascular endothelial growth factor (VEGF) in human gingival fibroblast culture in response to vesicles and outer membrane proteins from periodontopathic bacteria. Material and methods. Human gingival fibroblasts were stimulated with vesicles and outer membrane proteins from Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. In human gingival fibroblast cultures treated with or without resveratrol, VEGF production was evaluated by means of enzyme-linked immunosorbent assay and VEGF mRNA expression by means of reverse transcription polymerase chain reaction analysis. Vascular permeability enhancement was measured by the leakage of intravenously injected dye at the injection site of supernatant from cultures of human gingival fibroblasts stimulated by vesicles and outer membrane proteins. Results. Resveratrol significantly inhibited the increased production of VEGF by human gingival fibroblasts in response to vesicles and outer membrane proteins from periodontopathic bacteria, as shown by the detection of these proteins and their mRNA in vitro. Moreover, resveratrol treatment significantly decreased vascular permeability enhancement induced by supernatant from human gingival fibroblast cultures stimulated by vesicles and outer membrane proteins. Conclusions. Overall, these findings suggest that resveratrol inhibits production of VEGF by stimulated human gingival fibroblasts and can inhibit vascular permeability, suggesting a therapeutic role for it in pathogenic bacteria-induced periodontal inflammation.

Verified
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MNMaría Jesús Núñez-Iglesias
María Jesús Núñez-Iglesias
Silvia NovíoSilvia Novío
Silvia Novío
CGCarlota García
Carlota García
MPMª Elena Pérez-Muñuzuri
Mª Elena Pérez-Muñuzuri
MMMaría-Carmen Martínez
María-Carmen Martínez
MFManuel Freire-Garabal
Manuel Freire-Garabal
Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.

1 April 2010 in Clinical and Vaccine Immunology
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MNMaría J. NúñeZ
María J. NúñeZ
Silvia NovíoSilvia Novío
Silvia Novío
JSJuan Antonio SuárEz
Juan Antonio SuárEz
JBJosé Balboa
José Balboa
MFManuel Freire-Garabal
Manuel Freire-Garabal
Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans . Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.