DGH - Artigos em revistas internacionais
URI permanente para esta coleção:
Navegar
Entradas recentes
- Flavouring Group Evaluation 87, Revision 3 (FGE.87Rev3): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and related esters evaluated in FGE.47Rev1Publication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernández, María José; Grasl‐Kraupp, Bettina; Gundert‐Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Benigni, Romualdo; Degen, Gisela; Engel, Karl‐Heinz; Carfí, Maria; Martino, CarlaThe Panel on Food Additives and Flavourings (FAF) of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No. 1565/2000. The present consideration concerns a group of 19 bicyclic secondary alcohols, ketones and related esters evaluated by JECFA at the 63rd meeting. This revision of FGE.87 is made due to new information on annual production volume, allowing the calculation of maximised survey‐derived daily intake (MSDI) for 4,4a,5,6‐tetrahydro‐7‐methylnaphthalen‐2(3H)‐one [FL‐no: 07.136]. In addition, new data on uses and use levels for the substances [FL‐no: 07.089, 07.0136, 07.153 and 07.159] have been provided and considered for the estimation of exposure (mTAMDI approach). For [FL‐no: 07.136], the Panel agrees with the Procedure as applied by JECFA and with JECFA conclusion: ‘No safety concern at estimated levels of intake as flavouring substance’, when based on the MSDI approach. For the other 18 substances considered in FGE.87Rev3, the same conclusion was already drawn in FGE.87Rev2. For [FL‐no: 07.136], the mTAMDI exposure estimate is below the TTC for structural class II substances. Accordingly, no further data are required in the context of the current evaluation programme. For [FL‐no: 07.089, 07.153, 07.159], mTAMDI exposure estimates are above the TTC for structural class II substances; therefore, more reliable data on uses and use levels should be provided in order to refine the exposure assessment and to finalise their safety evaluation. For the remaining 15 substances, use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessments and to finalise the evaluation. Information on specifications for the materials of commerce is considered adequate for all 19 substances.
- Safety evaluation of the modification of the food additive enzymatically produced steviol glycosides (E 960c)Publication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Barat Baviera, José Manuel; Degen, Gisela; Gott, David; Herman, Lieve; Leblanc, Jean-Charles; Moldeus, Peter; Waalkens-Berendsen, Ine; Wölfle, Detlef; Civitella, Consuelo; Dino, Borana; Lunardi, Simone; Mech, Agnieszka; Multari, Samuele; Ruggeri, LauraThe EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety of a modified manufacturing process for the food additive enzymatically produced steviol glycosides (E 960c). The new process converts purified steviol glycosides extracted from Stevia rebaudiana leaves through enzymatic bioconversion catalysed by glucosyltransferase and sucrose synthase enzymes, both produced using three newly developed genetically modified strains of Escherichia coli (CDX‐044 W3110‐TKO, CDX‐045 W3110‐TKO and CDX‐047 W3110‐TKO). This modification of the manufacturing process yields two distinct preparations of steviol glycosides: SBP1, composed predominantly of rebaudioside M, and SBP2, composed predominantly of rebaudioside D. The modification leads to changes in the definition of the food additive, residual protein, residual solvents, microbiological criteria and particle size. The Panel concurred with the applicant's proposal to introduce two new entries in Commission Regulation (EU) No. 231/2012 corresponding to SBP1, predominantly rebaudioside M, and SBP2, predominantly rebaudioside D. The manufacturing process does not raise a safety concern since no viable cells nor DNA of the production strains remained in the final product; in addition, the food enzyme–total organic solid (TOS) are removed to at least 99%, and consequently, the exposure to the food enzyme–TOS via consumption of SPB1 and SPB2 can be considered negligible. The Panel considered that rebaudioside M and D produced by this new manufacturing process have the same physicochemical characteristics as the corresponding rebaudioside M and D present in E 960c(i), (ii) and (iii); therefore, the biological and toxicological data considered in previous evaluations will also apply to the safety assessment of SBP1 and SBP2. The Panel concluded that there is no safety concern with respect to the proposed modification of the food additive enzymatically produced steviol glycoside E 960c related to the use of the new genetically modified strains of E. coli in the production process of SBP1 and SBP2.
- Guidance on the scientific data requirements for an application for authorisation of a food additive submitted under Regulation (EC) No 1331/2008Publication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Gundert-Remy, Ursula; Ursula Gundert‐Remy; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Barmaz, Stefania; Carfì, Maria; Civitella, Consuelo; Gagliardi, Gabriele; Lodi, Federica; Martino, Carla; Mazzoli, Elena; Mech, Agnieszka; Rasinger, Josef Daniel; Rincon, Ana Maria; Ruggeri, Laura; Smeraldi, Camilla; Tard, Alexandra; Zakidou, PanagiotaThis guidance document applies to applications for a new authorisation as well as for a modification of an existing authorisation of a food additive, submitted under Regulation (EC) No 1333/2008. It defines the scientific data required to evaluate if the food additive is safe under the proposed conditions of use, in accordance with Articles 1 and 6 of Regulation (EC) No 1333/2008. The data requirements pertain to the characterisation of the proposed food additive, including the description of its identity, manufacturing process, specifications, stability, reaction and fate in foods and methods of analysis in food; the proposed uses and use levels and the dietary exposure; the safety data, including information on the genotoxic potential of the food additive, toxicological data other than genotoxicity and information on the safety for the environment. For the toxicological studies, a tiered approach is applied, for which the testing requirements, key issues and triggers are described. Applicants should provide data in accordance with this guidance document to support the safety assessment of the proposed food additive. Based on the submitted data, EFSA will assess the safety of the food additive in line with the risk assessment principles described in this document and conclude whether or not it presents risks to human health and to the environment, if applicable, under the proposed conditions of use.
- Evaluation of FASP for Mass Spectrometry-Based Untargeted Metabolomics analysis of urine samplesPublication . Mousa, Muath Khairi; Carvalho, Luis B.; Giddey, Alexander D.; Figueiredo, André; Al-Hroub, Hamza; Semreen, Mohammad H.; Uddin, Mohammed; Santos, Hugo M.; Soares, Nelson C.Filter-Aided Sample Preparation (FASP) is a well-established method in proteomics, yet its potential for the parallel recovery of metabolites remains largely unexplored. Herein, we evaluate the performance of FASP as a straightforward workflow for the simultaneous isolation of protein and corresponding metabolite fractions from a single urine sample. The FASP-based LC-MS/MS approach for both proteomics and metabolomics analysis identified 3,163 nonredundant peptides corresponding to 957 unique protein groups. The metabolomic profile comparison of three urine fractions, specifically FASP-concentrated, FASP flow-through, and raw samples, resulted in the identification of 176 common metabolites. Next, as a proof-of-concept, the FASP protocol was applied to compare the metabolomic profiles of clinical urine samples from healthy individuals (n = 13) and patients with Ta bladder cancer (n = 12). The metabolomic modulation was consistent with previously reported findings, highlighting perturbations in phenylacetate, purine, and tryptophan metabolism, as reflected by changes in metabolites such as adenosine monophosphate (AMP), phenylacetic acid, glutamine, cytosine, and l-tryptophan. FASP protocol can be effectively adapted for the concurrent profiling of both proteomic and metabolomic fractions from urine samples. Thus, FASP-based workflow represents a viable alternative for single-step sample preparation, facilitating subsequent quantitative multiomics data integration.
- Artificial Intelligence and multiomics beyond PSA screening in African and Middle Eastern prostate cancer patientsPublication . Al-Shahrabi, Rula; Alkhnbashi, Omer S.; Almarri, Rauda S.B.; Ahmad, Sarfraz; Soares, Nelson C.; Al Shareef, ZainabProstate cancer (PCa) remains a major global health burden, with incidence rising as populations age. The molecular, histological, and patient-specific heterogeneity of PCa underscores the urgent need for advanced strategies to improve detection and risk stratification. This review highlights how multiomics integration, including transcriptomics, DNA methylation, proteomics, and metabolomics, combined with artificial intelligence (AI), can validate biological mechanisms across molecular layers, thereby enhancing diagnostic reliability and biological relevance. While prostate-specific antigen (PSA) testing has significantly shaped PCa epidemiology, its limited specificity and sensitivity have led to widespread overdiagnosis and overtreatment, particularly of indolent tumors. These limitations are especially pronounced in underrepresented populations, notably men of African descent and those in the Middle East and North Africa (MENA) region, where PSA-based screening demonstrates reduced effectiveness. Despite advances in biomarker discovery, current datasets lack sufficient ethnic and regional diversity, raising concerns about the clinical validity and equity of AI-driven models. We argue that equitable precision oncology requires not only technological innovation but also the development of inclusive, demographically representative datasets. This review offers a forward-looking perspective on advancing PCa screening and stratification beyond PSA, with a particular emphasis on addressing the unmet clinical needs of African and Middle Eastern patients.
- ARPE-19-A Stable Cell Line Expressing a Variant of Unknown Significance in the NPC1 GenePublication . Monteiro, Beatriz; Peixoto, Maria Inês; Ortigoza-Escobar, Juan Darío; Alves, Mariana; Sandiares, Ana Catarina; Gonçalves, Mariana; Vaz Moreira, Luciana; Coutinho, Maria Francisca; Matos, Liliana; Alves, Sandra; Encarnação, MarisaBackground: Niemann-Pick type C is a lysosomal storage disorder that results from pathogenic variants in the NPC1 gene or in some cases from NPC2 pathogenic alterations. The disease presents a remarkable clinical variability that in some cases resembles common diseases, often resulting in a diagnostic odyssey or at least delaying proper diagnosis. In addition, the NPC1 gene is highly polymorphic, and consequently, when missense variants are identified after gene sequencing, accurate classification of their pathogenicity is essential to ensure appropriate access to available therapies and to provide reliable genetic counseling. Objectives: To get insights into the pathogenicity of a novel variant in NPC1, p.Cys800Ser, we created stable cell lines expressing this variant, in parallel with cell lines expressing the NPC1 wild-type and NPC1 pathogenic variants. Methods: We leveraged an isogenic cell line in which the NPC1 gene was knocked down and subsequently infected it with retroviruses carrying NPC1-WT and NPC1 variants C-terminally fused with an mNeonGreen tag. Three different NPC1 variants were included in this study: two known pathogenic variants, p.Ala1035Val and p.Pro1007Ala, and the novel p.Cys800Ser, whose significance was unknown. Results: We observed in the stable cell line expressing NPC1 p.Cys800Ser that the mutated NPC1 protein is transported to the lysosome similarly to the p.Pro1007Ala variant and affects lysosomal distribution. Conclusions: Using this approach, we could analyze the pathogenicity of each variant separately and these cell lines could be used for personalized medicine-based approaches and multi-omic studies.
- Proteomic and metabolomic profiling of methicillin-resistant Staphylococcus aureus associated with invasive vs. non-invasive infections: uncovering key biomarkers and pathogenic pathwaysPublication . Boucherabine, Syrine; Giddey, Alexander D.; Nassar, Rania; Mohamed, Lobna; Verma, Subham; Soares, Nelson C.; Senok, AbiolaIntroduction: Understanding the behavioral differences between invasive and non-invasive methicillin-resistant Staphylococcus aureus (MRSA) is essential for unraveling infection mechanisms and identifying biomarkers with translational potential. This study compared the proteomic and metabolomic profiles of MRSA isolates from diverse clinical presentations to uncover distinct molecular signatures. Methods: Invasive isolates were obtained from blood cultures (n = 23), while non-invasive isolates were derived from superficial skin infections (n = 49) and nasal colonizers (n = 24) from screening swabs. Proteins and metabolites were simultaneously extracted using a dual-phase methanol-based protocol. Proteomic analysis was performed on the Orbitrap Exploris 480, while metabolites were characterized using a TimsTOF mass spectrometer with an Apollo II electrospray ionization source. Data-independent acquisition (DIA) was applied, with peptide assignment carried out in DIA-NN and metabolite analysis using MetaboScape® 4.0. Results: Across all isolates, 2,000 proteins and 150 metabolites were identified. Comparative analysis revealed that invasive isolates exhibited consistently higher levels of two metabolites (sphinganine and phosphoserine) and one protein (staphylococcal secretory antigen SsaA2) compared to non-invasive. In contrast, three metabolites (cytidine, benzoic acid, and guanosine) and two proteins (small ribosomal subunit protein bS20 and bifunctional autolysin) were significantly reduced in invasive isolates. These findings highlight key molecular differences underpinning invasive potential in MRSA, providing insights into candidate diagnostic and therapeutic biomarkers. These findings highlight critical biological differences between invasive and non-invasive MRSA, offering valuable insights into potential diagnostic and therapeutic biomarkers.
- Dissecting the impact of SHC-1 inhibitors in enhancing the plasma membrane abundance of the CFTR channel across epithelial cell modelsPublication . Barros, Patricia; Pereira, Mariana F.L.; Tomilov, Alexey; Cortopassi, Gino; Jordan, Peter; Matos, PauloPlasma membrane (PM) ion transport depends on tightly regulated trafficking and activation of ion channels. For the cystic fibrosis transmembrane conductance regulator (CFTR), dysregulation caused by tobacco smoke or chronic inflammation contributes to diseases such as chronic obstructive pulmonary disease (COPD). We previously showed that phosphorylation of CFTR at tyrosine 512 (Y512) by spleen tyrosine kinase promotes its internalization via the MAPK/SHC-1 pathway in CFBE airway cells. Here, we investigated whether this mechanism is conserved in other epithelial models and whether inhibition of SHC-1 increased CFTR abundance at the PM. CFTR surface levels were assessed in CFBE, 16HBE, and Caco-2 cells using biotinylation and immunoblotting after treatment with MEK inhibitor selumetinib, SHC-1 inhibitor idebenone (IDE), or its novel inhibitor 110#3. MAPK activity was evaluated by ERK phosphorylation. We found that MAPK/SHC-1-dependent CFTR internalization was conserved in 16HBE and Caco-2 cells. In CFBE cells, treatment with IDE or 110#3 increased PM CFTR levels, but also unrelated PM proteins (GLUT1 and E-cadherin). No significant effects were observed in 16HBE or Caco-2 cells. These findings suggest CFBE cells may not fully recapitulate endogenous CFTR trafficking and raise the possibility that selective SHC-1/pY512-CFTR inhibitors may modulate CFTR trafficking in COPD and other CFTR-related diseases.
- Genetic variants in red blood cell adhesion-related genes influence the severity of sickle cell anemia in a malaria-endemic regionPublication . Matos, Irina; Santos, Brígida; Gonçalves, Elisângela; Lopes, Pedro; Brito, Miguel; Arez, Ana Paula; Faustino, PaulaBackground: Sickle cell anemia (SCA) is a genetic disease marked by abnormal hemoglobin S and sickle-shaped red blood cells. It is highly prevalent in sub-Saharan Africa, especially in Angola, where SCA and malaria are major causes of childhood mortality. This study aimed to explore whether genetic variants in genes associated with red blood cell adhesion to the vascular endothelium influence the manifestations of SCA in Angolan pediatric patients in the context of malaria. Methods and results: The study enrolled 65 pediatric SCA patients living in Luanda or Caxito. Their clinical, hematological, and biochemical profiles were monitored through longitudinal pediatric follow-up appointments. Fifteen polymorphic sites were genotyped in CD36 and ICAM-1 genes using PCR, Sanger sequencing, and fragment analysis by capillary electrophoresis. Malaria infection was evaluated by detecting Plasmodium species DNA through PCR analysis of blood spot samples. The CD36 variant rs3211891_C is revealed for the first time as a potential modulator of anemia severity in SCA. Additionally, the CD36 variant rs3211938_G, along with the ICAM-1 variants rs5491_T and rs5496_A, significantly impacted the severity of the hematological phenotype in SCA. Furthermore, SCA patients carrying the ICAM-1 rs5494_T variant showed a 5.63-fold increased risk of having malaria infection compared to those with the wild-type genotype. Conclusions: This study enhances our understanding of genetic modifiers of red blood cell adhesion to the vascular endothelium and their influence on the severity of pediatric SCA in the context of frequent concomitant malaria infection in Angola.
- The Genetics of Iron Metabolism on Biochemical and Hematological Phenotypes of Heart FailurePublication . Barbosa, Mário; Aguiar, Laura; Matias, Ana; Ferreira, Joana; Caldeira, João; Melício, Ana; Faustino, Paula; Menezes Falcão, Luiz; Bicho, Manuel; Inácio, ÂngelaHeart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure.