Genetic 3’UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight

Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3′untranslated regions (3′UTRs). Therefore, 3′UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3′UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed. The association of genotypic data with pigmentation traits was analysed via logistic regression. Web-based tools for predicting the effect of genetic variants in microRNA-binding sites in 3′UTR gene regions were also used. Seven 3′UTR SNPs showed a potential implication in melanoma risk phenotypes. This association is especially noticeable for two of them, rs2325813 in the MLPH gene and rs752107 in the WNT3A gene. These two SNPs were predicted to disrupt a miRNA-binding site and to impact on miRNA-mRNA interaction. To our knowledge, this is the first time that these two 3′UTR SNPs have been associated with sun-sensitivity traits. We state the potential implication of these SNPs in human pigmentation and sensitivity to sunlight, possibly as a result of changes in the level of gene expression through the disruption of putative miRNA-binding sites

Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

Background Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. Methods We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. Results We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. Conclusions To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection

Experience of 10 years in routine trans operative endoscopy and calibration in fundoplication due to gastroesophageal reflux disease

Background: Endoscopy and intraoperative calibration in fundoplication for gastroesophageal reflux disease (GERD), confirm an adequate technique avoiding postoperative failure. Intraoperative changes and morbidity in routine use are unknown.Methods: Retrospective study in a single center, data were taken primarily from electronic archive medical records. A total of 899 who underwent fundoplication surgery with endoscopy and/or routine intraoperative calibration due to GERD met the required criteria between 1 January 2010 and 31 December 2020. The primary objective was to identify the number of calibration and intraoperative endoscopy findings. Also, the morbidity associated with its routine use was analyzed.Results: Over a 10-year study period, the most frequent calibration in the Nissen Fundoplication was 60Fr in 472 cases (61.4 %). The most used calibration in Toupet Fundoplication was 60Fr in 26 cases (21.1%). Endoscopy was performed in 786 patients (71.38%), of which; 3 patients (0.3%) required changes, secondary to fundoplication rotation in 2 patients (0.2%) and redundant gastric fundus in 1 patient (0.1%).Conclusions: Routine intraoperative calibration and endoscopy achieved excellent results in 96.8% of fundoplication’s, ensuring adequate esophageal position and corroborating an adequate intraoperative technique; decreasing the rate of failures and immediate postoperative dysphagia

Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12–1.48; p-value = 4×10−4). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocyte

Lipid nanoparticle of polymyxin

A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fraction, and one or more surfactants. The lipid nanoparticle is useful in the prevention and/or treatment of respiratory tree infectionsPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Nanopartícula lipídica de polimixina

La presente invención se relaciona con una nanopartícula lipídica que comprende al menos un antibiótico de la familia de las polimixinas, una composición farmacéutica que comprende dicha nanopartícula y el uso de la nanopartícula en la prevención y/o tratamiento de infecciones del árbol respiratorioPeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)T3 Traducción de patente europe

Nanopartícula lipídica de polimixina

[EN] The invention relates to a lipid nanoparticle comprising at least one antibiotic from the polymyxin family, a lipid fraction and one or more surfactants, and to the use of the nanoparticle in the prevention and/or treatment of infections in the respiratory system[ES] La presente invención se relaciona con una nanopartícula lipídica que comprende al menos un antibiótico de la familia de las polimixinas, una fracción lipídica y uno o más tensioactivos,y el uso de la nanopartícula en la prevención y/o tratamiento de infecciones del árbol respiratorio[FR] La présente invention concerne une nanoparticule lipidique qui comprend au moins un antibiotique de la famille des polymyxines, une fraction lipidique et un ou plusieurs tensioactifs, ainsi que l'utilisation de ladite nanoparticule pour la prévention et/ou le traitement d'infections du système respiratoirePeer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Lipid nanoparticle of polymyxin

A lipid nanoparticle that includes at least one antibiotic from the polymyxin family, a lipid fraction, and one or more surfactants. The lipid nanoparticle is useful in the prevention and/or treatment of respiratory tree infections.Peer reviewedBiopraxis Research AlE, Praxis Pharmaceutical, S.A., Fundació d'lnvestigació Sanitaria de Les llles Balears, Universidad del Pais Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), Universidad de Barcelona, Consejo Superior de Investigaciones Científicas (España)B2 Patente con examen previ