Molecular Biology Center

Málaga, Spain

Molecular Biology Center

Málaga, Spain
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Fernandez-Garcia C.-E.,Fundacion Jimenez Diaz Autonoma University | Burillo E.,Fundacion Jimenez Diaz Autonoma University | Lindholt J.S.,University of Southern Denmark | Martinez-Lopez D.,Fundacion Jimenez Diaz Autonoma University | And 10 more authors.
Journal of Thrombosis and Haemostasis | Year: 2017

Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3 plasma levels are associated with AAA presence and progression. Summary: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA. Results Increased ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients’ plasma (n = 478) compared with control plasma (n = 176), which persisted after adjustment for risk factors (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 3.27, 8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho, 0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors (adjusted hazard ratio, 1.55; 95% CI, 1.11, 2.15). Conclusions In addition to its hepatic expression, ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with the presence and progression of AAA, suggesting its potential role as a biomarker of AAA. © 2016 International Society on Thrombosis and Haemostasis


Dai S.-S.,Molecular Biology Center | Wang H.,Chongqing Medical University | Yang N.,Molecular Biology Center | An J.-H.,Molecular Biology Center | And 5 more authors.
Journal of Experimental Medicine | Year: 2013

The bone marrow-derived cell (BMDC)-associated inflammatory response plays a key role in the development of acute lung injury (ALI). Activation of adenosine A2A receptor (A2AR) is generally considered to be antiinflammatory, inhibiting BMDC activities to protect against ALI. However, in the present study, we found that in a mouse model of neurogenic ALI induced by severe traumatic brain injury (TBI), BMDC A2AR exerted a proinflammatory effect, aggravating lung damage. This is in contrast to the antiinflammatory effect observed in the mouse oleic acid-induced ALI model (a nonneurogenic ALI model.) Moreover, the A2AR agonist CGS21680 aggravated, whereas the antagonist ZM241385 attenuated, the severe TBI-induced lung inflammatory damage in mice. Further investigation of white blood cells isolated from patients or mouse TBI models and of cultured human or mouse neutrophils demonstrated that elevated plasma glutamate after severe TBI induced interaction between A2AR and the metabotropic glutamate receptor 5 (mGluR5) to increase phospholipase C-protein kinase C signaling, which mediated the proinflammatory effect of A2AR. These results are in striking contrast to the well-known antiinflammatory and protective role of A2AR in nonneurogenic ALI and indicate different therapeutic strategies should be used for nonneurogenic and neurogenic ALI treatment when targeting A2AR. © 2013 Dai et al.


Wang J.-C.,Quest Diagnostics Nichols Institute | Ross L.,Quest Diagnostics Nichols Institute | Mahon L.W.,Quest Diagnostics Nichols Institute | Owen R.,Quest Diagnostics Nichols Institute | And 20 more authors.
European Journal of Human Genetics | Year: 2015

Copy neutral segments with allelic homozygosity, also known as regions of homozygosity (ROHs), are frequently identified in cases interrogated by oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence of ROHs may be because of parental relatedness, chromosomal recombination or rearrangements and provides important clues regarding ancestral homozygosity, consanguinity or uniparental disomy. In this study of 14 574 consecutive cases, 832 (6%) were found to harbor one or more ROHs over 10 Mb, of which 651 cases (78%) had multiple ROHs, likely because of identity by descent (IBD), and 181 cases (22%) with ROHs involving a single chromosome. Parental relatedness was predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy (isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5 cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive disorders were confirmed in seven of nine cases from eight families because of the finding of suspected gene within a ROH. This study demonstrates that ROHs are much more frequent than previously recognized and often reflect parental relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases. © 2015 Macmillan Publishers Limited All rights reserved.


Mateos M.E.,University of Cordoba, Spain | Beyer K.,University of Barcelona | Lopez-Laso E.,University of Cordoba, Spain | Siles J.L.,Molecular Biology Center | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2013

Mutations in the gene encoding glypican (GPC) 3 appear to be responsible for most cases of Simpson-Golabi-Behmel syndrome type 1. Duplication of the GPC4 gene has also been associated to this syndrome; however, no duplications involving GPC3 have been related. We describe a family that harbors a novel exon 2-4 duplication event leading to a truncating germline mutation of the GPC3 gene that, to our knowledge, has not been previously reported. GPC3 transcripts that carry this duplication bear non-functional proteins making its pathogenic role highly probable. The absence of a functional GPC3 may alter the normal differentiation of embryonal mesodermal tissues predisposing to the development of embryonal tumors, as the index case studied who developed a hepatoblastoma at age 9 months. © 2012 Wiley Periodicals, Inc.


Nkenfou C.N.,Molecular Biology Center | Nkenfou C.N.,University of Yaounde I | Mawabo I.K.,Molecular Biology Center | Mawabo I.K.,University of Dschang | And 6 more authors.
International Journal of Mycobacteriology | Year: 2015

Objective/background: The latest incidence of tuberculosis (TB) (per 100,000 people) in Cameroon was 243.00 as of 2011. Over the past 21. years, the value for this indicator has fluctuated between 112.00 in 1990 and 320.00 in 2003. Worldwide, this incidence has also increased, bringing back TB as a reemerging disease. On the same note, resistance to anti-TB drugs has increased, urging the search for new molecules. Methods: This study was carried out to evaluate the antimycobacterial activity of six medicinal plants on the virulent strain, H37Rv, using the microplate alamarBlue assay. Mycobacterium tuberculosis (H37Rv strain) was incubated with decreased concentrations of six plant extracts, ranging from 250. μg/mL to 31.25. μg/mL. After 7. days of incubation at 37. °C, the effects of these plant extracts on the viability of the mycobacteria were evaluated. For each plant extract, the minimal inhibitory concentration was determined. Results: The results showed that the compounds MBC1, MBC24, MBC68, MBC81, MBC117, and MBC118 were the best candidates with minimal inhibitory concentrations of 31.25, 62.5, 125, 62.5, and 125. μg/mL, respectively. Conclusion: These results confirm and validate the traditional use of these plants to treat respiratory diseases, which could be good sources and alternatives of plant metabolites for anti-TB-drug development. © 2015 Asian African Society for Mycobacteriology.


PubMed | Fundacion Jimenez Diaz Autonoma University, Heart and Vascular Surgery University Hospital of Odense, Copenhagen University, Molecular Biology Center and University Paris Diderot
Type: | Journal: Journal of thrombosis and haemostasis : JTH | Year: 2016

Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology.To define extrahepatic sources of ficolin-3 in AAA, and investigate the role of ficolin-3 as a biomarker of AAA presence and progression.Microvesicles (exosomes and microparticles) were isolated from culture conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA.Increased Ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, while little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients plasma (n=478) compared with control plasma (n=176), which persisted after adjustment for risk factors [Adj. OR=5.29 (95% CI.:3.27;8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho=0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors [Adj. HR=1.55 (95% CI: 1.11;2.15)].In addition to its hepatic expression, Ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with AAA presence and progression, suggesting its potential role as a biomarker of AAA. This article is protected by copyright. All rights reserved.


PubMed | Childrens Hospital Central California, The University of Oklahoma Health Sciences Center, University of Miami, Quest Diagnostics Nichols Institute and 3 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2015

Copy neutral segments with allelic homozygosity, also known as regions of homozygosity (ROHs), are frequently identified in cases interrogated by oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence of ROHs may be because of parental relatedness, chromosomal recombination or rearrangements and provides important clues regarding ancestral homozygosity, consanguinity or uniparental disomy. In this study of 14574 consecutive cases, 832 (6%) were found to harbor one or more ROHs over 10Mb, of which 651 cases (78%) had multiple ROHs, likely because of identity by descent (IBD), and 181 cases (22%) with ROHs involving a single chromosome. Parental relatedness was predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy (isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5 cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive disorders were confirmed in seven of nine cases from eight families because of the finding of suspected gene within a ROH. This study demonstrates that ROHs are much more frequent than previously recognized and often reflect parental relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases.


PubMed | University of Yaounde I, University of Dschang and Molecular Biology Center
Type: Journal Article | Journal: International journal of mycobacteriology | Year: 2016

According to estimates by the World Health Organization, there were 9.6 million new tuberculosis (TB) cases in 2014: 5.4 million among men, 3.2 million among women, and 1.0 million among children. There were also 1.5 million TB deaths. Although there are potent anti-TB molecules, the misuse of these drugs in addition to inconsistent or partial treatment have led to the development of multidrug-resistant TB and extensively drug-resistant TB. It is established that plants harbor microorganisms, collectively known as endophytes, which also produce metabolites. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel and active compounds. The present study was aimed to investigate the antimycobacterial activity of the crude extract and compounds isolated from Penicillium sp. endophyte associated with Garcinia nobilis against Mycobacterium smegmatis.Liquid culture obtained from the fermentation of Penicillium sp. was extracted using ethylacetate and the liquid chromatography-mass spectrometry monitored fractionation of crude extracts yielded six compounds. Their structures were elucidated with spectroscopic analyses including two-dimensional nuclear magnetic resonance, high resolution mass spectrometry by dereplication using Antibase, and by comparison to literature data. All compounds and the crude extract from the liquid medium were evaluated for their antimycobacterial activity against M. smegmatis.In this study, the activity of penialidins A-C (1-3), citromycetin (4), p-hydroxy phenyl glyoxalaldoxime (5), and Brefeldin A (6) were tested against nonpathogenic M. smegmatis. Penialidin C was the most active compound with a minimum inhibitory concentration of 15.6g/mL.Isolated compounds from Penicillium sp. harbored in G. nobilis exhibited promising antimycobacterial activity against M. smegmatis thus supporting the immensity of the potential of antimycobacterial drug discovery from endophytes from medicinal plants. Penialidin C could further be investigated for antimycobacterial drug development.


PubMed | University of Yaounde I, University of Dschang and Molecular Biology Center
Type: Journal Article | Journal: International journal of mycobacteriology | Year: 2016

The latest incidence of tuberculosis (TB) (per 100,000 people) in Cameroon was 243.00 as of 2011. Over the past 21 years, the value for this indicator has fluctuated between 112.00 in 1990 and 320.00 in 2003. Worldwide, this incidence has also increased, bringing back TB as a reemerging disease. On the same note, resistance to anti-TB drugs has increased, urging the search for new molecules.This study was carried out to evaluate the antimycobacterial activity of six medicinal plants on the virulent strain, H37Rv, using the microplate alamarBlue assay. Mycobacterium tuberculosis (H37Rv strain) was incubated with decreased concentrations of six plant extracts, ranging from 250 g/mL to 31.25 g/mL. After 7 days of incubation at 37 C, the effects of these plant extracts on the viability of the mycobacteria were evaluated. For each plant extract, the minimal inhibitory concentration was determined.The results showed that the compounds MBC1, MBC24, MBC68, MBC81, MBC117, and MBC118 were the best candidates with minimal inhibitory concentrations of 31.25, 62.5, 125, 62.5, and 125 g/mL, respectively.These results confirm and validate the traditional use of these plants to treat respiratory diseases, which could be good sources and alternatives of plant metabolites for anti-TB-drug development.

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