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1.
An ancestral molecular response to nanomaterial particulates.
Del Giudice, G, Serra, A, Saarimäki, LA, Kotsis, K, Rouse, I, Colibaba, SA, Jagiello, K, Mikolajczyk, A, Fratello, M, Papadiamantis, AG, et al
Nature nanotechnology. 2023;(8):957-966
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Abstract
The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.
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Observational pilot study: A comparison of amino acids and derangement of intestinal function between healthy ageing subjects and patients affected by chronic kidney disease stage CKD3b-4 in conservative management.
Bolasco, P, Aquilani, R, Maestri, R, Esposito, MP, Deiana, ML, Cadeddu, M, Secci, R, Casu, B, Serra, A, Iadarola, P, et al
Clinical nutrition ESPEN. 2023;:10-19
Abstract
BACKGROUND AND AIMS A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. METHODS Eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6 ± 0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total amino acids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. RESULTS Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89 g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. CONCLUSIONS This study confirms the finding in aged patients of an alteration in plasmatic levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.
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Parental risk factors for oesophageal atresia.
Kapapa, M, Weber, D, Serra, A
Journal of the Formosan Medical Association = Taiwan yi zhi. 2023;(9):932-939
Abstract
BACKGROUND An Oesophageal atresia (OA) affects almost 1 in 3500 newborn and its aetiology for development between 4th to 6th pregnancy weeks had not yet been clarified. METHODS This retrospective, observational control group-supported (n = 30) examination was performed with OA mothers (n = 20) who were interrogated via specialized questionnaires and interviews to evaluate data on medical pregnancy history including hormonal treatment, changing of life habits (nutrition, diet, medication), drug consumption (alcohol, smoking, illicit drugs) as well as exposure to nuclear waste or poisonous substance exposition. Aim was to assess risk factors during pregnancy and in particular in the first trimester. RESULTS The body mass index (BMI) prior pregnancy of OA mothers was significant lower (p = 0.022) and the number of mothers with obesity (BMI>30) did not differ to control group mothers (p = 0.081). They had additionally more pre-existing illnesses (p = 0.009) and allergies (p = 0.001). Control group mothers changed dietary habits with higher meat (p = 0.032) and caffeine intake (p = 0.012) compared to OA mothers, which had higher rates of abnormalities during pregnancy (p < 0.001) and 38.7% of them suffered of ≥1 abortion in the past. The ethnical background of OA mothers was more often German (p < 0.033), while OA fathers had a lower socioeconomic status (p = 0.039). CONCLUSION Maternal factors like previous abortions, obesity and immunological predispositions like existence of allergies combined with increased daily dairy consumption influenced obviously the occurrence of OA.
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Plant-derived nootropics and human cognition: A systematic review.
Lorca, C, Mulet, M, Arévalo-Caro, C, Sanchez, MÁ, Perez, A, Perrino, M, Bach-Faig, A, Aguilar-Martínez, A, Vilella, E, Gallart-Palau, X, et al
Critical reviews in food science and nutrition. 2023;(22):5521-5545
Abstract
Substances with modulatory capabilities on certain aspects of human cognition have been revered as nootropics from the dawn of time. The plant kingdom provides most of the currently available nootropics of natural origin. Here, in this systematic review, we aim to provide state-of-the-art information regarding proven and unproven effects of plant-derived nootropics (PDNs) on human cognition in conditions of health and disease. Six independent searches, one for each neurocognitive domain (NCD), were performed in parallel using three independent scientific library databases: PubMed, Cochrane and Scopus. Only scientific studies and systematic reviews with humans published between January 2000 and November 2021 were reviewed, and 256 papers were included. Ginkgo biloba was the most relevant nootropic regarding perceptual and motor functions. Bacopa monnieri improves language, learning and memory. Withania somnifera (Ashwagandha) modulates anxiety and social-related cognitions. Caffeine enhances attention and executive functions. Together, the results from the compiled studies highlight the nootropic effects and the inconsistencies regarding PDNs that require further research.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2021137.
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Biomarkers of nanomaterials hazard from multi-layer data.
Fortino, V, Kinaret, PAS, Fratello, M, Serra, A, Saarimäki, LA, Gallud, A, Gupta, G, Vales, G, Correia, M, Rasool, O, et al
Nature communications. 2022;(1):3798
Abstract
There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identify mRNA-based toxicity markers and extensively replicate them in multiple independent datasets. We find that models based on combinations of omics-derived features and material intrinsic properties display significantly improved predictive accuracy as compared to physicochemical properties alone.
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Magnesium-based resorbable scaffold vs permanent metallic sirolimus-eluting stent in patients with ST-segment elevation myocardial infarction: 3-year results of the MAGSTEMI randomised controlled trial.
Ortega-Paz, L, Brugaletta, S, Gomez-Lara, J, Alfonso, F, Cequier, A, Romaní, S, Bordes, P, Serra, A, Iñiguez, A, Salinas, P, et al
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2022;(5):e389-e396
Abstract
BACKGROUND The long-term safety and performance of magnesium-based bioresorbable scaffolds (MgBRS) in ST-segment-elevation myocardial infarction (STEMI) patients are uncertain. AIMS The aim of this study was to report the 3-year clinical outcomes of the MAGSTEMI trial. METHODS This investigator-driven, multicentre, randomised, single-blind, controlled trial randomised STEMI patients 1:1 to MgBRS or to permanent metallic sirolimus-eluting stents (SES) at 11 academic centres. The main secondary endpoints included device-oriented composite endpoints (DoCE) and patient-oriented composite endpoints (PoCE), their individual components, any bleeding, and device thrombosis rate. All endpoints were defined according to the Academic Research Consortium. Events were adjudicated by an independent committee. RESULTS Three-year clinical follow-up was obtained in 142 (90.0%) patients. At 3-year follow-up, MgBRS were associated with a higher rate of DoCE than SES (13 [17.6%] vs 5 [6.6%], diff -11.0 [95% CI: -21.3 to -0.7]; p=0.038). This difference was driven by an increased incidence of DoCE within the first year of follow-up. In the landmark analysis, there was no difference between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000). The difference in the rate of DoCE was driven by a higher incidence of target lesion revascularisation (TLR) in the MgBRS group compared to SES (12 [16.2%] vs 4 [5.3%]; diff -10.9% [95% CI: -20.7 to -1.2]; p=0.030). The difference in TLR was observed during the first year, with no further differences observed between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000). CONCLUSIONS At 3-year follow-up, MgBRS were associated with a higher rate of TLR, which was clustered within the first year, compared to SES.
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Does meconium contaminated amniotic fluid affect intestinal wall thickness and functional outcome in patients with anterior abdominal wall defects?
Kapapa, M, Rieg, T, Serra, A
African journal of paediatric surgery : AJPS. 2022;(1):46-51
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Abstract
BACKGROUND Gastroschisis (GS) and omphalocele (OC) are congenital abdominal wall defects, the main difference between is the direct exposure of intestinal loops in amniotic fluid in children with a GS. This leads to a reduced primary closure rate and a higher number of intraoperative abnormalities and post-operative complications. AIMS AND OBJECTIVES We analysed abdominal wall defect patients over an 11-year period, aiming to assess the influence of meconium-contaminated amniotic fluid. This study has different objectives to show the consequence of functional outcome of abdominal wall defects (AWD) children in reliance to colour of amniotic fluid, to assess the effect of reduced bowel exposure time to meconium contaminated amniotic fluid on edematous inflammatory thickening of the bowel loops, to show an positively influence in the number of primary AWD closures, to demonstrate a reduced incidence of post-natal complications and to verify a better outcome of OC children because of failing exposure to amniotic fluid. METHODS A retrospective, observational case-control design was used to compare GS (n = 36) and OC (n = 18) children. Physical data, colour of amniotic fluid, pre- and perinatal problems, operative complications and surgical technique, post-operative complications, duration of intensive care unit (ICU) stay, mechanical ventilation, parenteral nutrition, commencement of oral feeding and total hospital stay were collected. Data were analysed with descriptive methods, t-test and non-parametric tests such as Wilcoxon and Kruskal-Wallis were performed in addition to the analysis of variance, including post hoc testing accepting a confidence interval of 95% (P < 0.05) by using IBM SPSS software, version 23 (IBM, Illinois, USA). RESULTS Rate of meconium-contaminated amniotic fluid is significantly higher in GS compared to OC (P < 0.001), delivery problems such as congenital infections are also significantly higher (P < 0.001), this yields in significantly more bowel loops anomalies and problems during surgery (P < 0.036) but had no significant influence on primary abdominal wall closures rate (P = 0.523). The post-surgical outcome of OC was significantly better as compared to GS. Within the GS, those with swollen intestines had significantly longer ICU stays (P = 0.045) due to extended mechanical ventilation (P = 0.007), parenteral nutrition (P = 0.011) and delayed initiation of oral feeding (P < 0.001. Same results were found for the duration of ICU stay (P = 0.008), mechanical ventilation (P = 0.006), parenteral nutrition (P = 0.011) and delayed initiation of oral feeding (P < 0.001) in secondary closures as compared to primary abdominal wall closures in the GS group. CONCLUSIONS Worsen functional short-term outcome of GS children was directly addicted to meconium contamination of amniotic fluid due to swollen intestines and because of this more post-surgical problem including significantly extended hospital stays were observed.
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Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.
Murtas, S, Aquilani, R, Fiori, G, Maestri, R, Iadarola, P, Graccione, C, Contu, R, Deiana, ML, Macis, F, Secci, R, et al
Nutrients. 2022;(17)
Abstract
(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.
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Influence of FLG loss-of-function mutations in host-microbe interactions during atopic skin inflammation.
Oláh, P, Szlávicz, E, Kuchner, M, Nemmer, J, Zeeuwen, P, Lefèvre-Utile, A, Fyhrquist, N, Prast-Nielsen, S, Skoog, T, Serra, A, et al
Journal of dermatological science. 2022;(3):132-140
Abstract
BACKGROUND Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive. OBJECTIVE In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD. METHODS Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (ADMut) (n = 15), along with matched wild-type (ADWt) patients and healthy controls. Detailed clinical characterization, microarray gene expression and 16 S rRNA-based microbial marker gene data were generated and analyzed. RESULTS In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of ADWt demonstrated the specific upregulation of pro-inflammatory cytokines and T-cell proliferation. S. aureus dominated the microbiome in both patient groups, however, shifting microbial communities could be observed when comparing healthy with non-lesional ADWt or ADMut skin, offering the opportunity to identify microbe-associated transcriptomic signatures. Moreover, an AD core signature with 28 genes, including CCL13, CCL18, BTC, SCIN, RAB31 and PCLO was identified. CONCLUSIONS Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.
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Type 2 diabetes preventive effects with a 12-months sardine-enriched diet in elderly population with prediabetes: An interventional, randomized and controlled trial.
Díaz-Rizzolo, DA, Serra, A, Colungo, C, Sala-Vila, A, Sisó-Almirall, A, Gomis, R
Clinical nutrition (Edinburgh, Scotland). 2021;40(5):2587-2598
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Older people have a higher risk of developing Type 2 diabetes (T2D) due to the possibility of β-cell dysfunction due to ageing. Sardines are believed to be protective against the development of T2D. Therefore, this randomised controlled trial evaluated the preventative effects of a sardine-rich diet in elderly prediabetic patients. For one year, both the sardine group (SG) and control group (CG) followed a T2D prevention diet, with the SG consuming 200 g of sardines each week. Both groups improved body weight, BMI, waist and hip circumference, and body composition. Taurine, EPA, DHA, omega-3 fatty acid, calcium, iodine, zinc, phosphorous and fluoride, vitamin B12 and D, and lycopene and tocopherols were found to be higher in the SG than the CG, indicating the sardines were protective against T2D. In SG, HDL cholesterol and adiponectin levels were significantly increased, and blood pressure and triglycerides were decreased, signalling a reduced risk of T2D and cardiovascular disease. In addition, SG showed a reduction in HOMA-IR and an Omega-3 fatty acid was substituted for Omega-6 fatty acids in the erythrocyte membrane, suggesting a reduced risk of T2D. Further robust research is required to confirm the protective effect of a sardine-enriched diet against T2D. It may be useful to healthcare providers to comprehend how a sardine-enriched diet could improve obesity, T2D and CVD markers in pre-diabetic elderly patients.
Abstract
BACKGROUND Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. HYPOTHESIS The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age. DESIGN 152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541). RESULTS 152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001). CONCLUSION We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.