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Glioblastoma (GBM) represents a formidable challenge in oncology, characterized by aggressive proliferation and poor prognosis. Iron metabolism plays a critical player in GBM progression, with dysregulated iron uptake and utilization contributing to tumor growth and therapeutic resistance. Iron's pivotal role in DNA synthesis, oxidative stress, and angiogenesis underscores its significance in GBM pathogenesis. Elevated expression of iron transporters, such as transferrin receptor 1 (TfR1), highlights the tumor's reliance on iron for survival. Innovative treatment strategies targeting iron dysregulation hold promise for overcoming therapeutic challenges in GBM management. Approaches such as iron chelation therapies, induction of ferroptosis to nanoparticle-based drug delivery systems exploit iron-dependent vulnerabilities, offering avenues for enhance treatment efficacy and improve patient outcomes. As research advances, understanding the complexities of iron-mediated carcinogenesis provides a foundation for developing precision medicine approaches tailored to combat GBM effectively. This review explores the intricate relationship between iron metabolism and GBM, elucidating its multifaceted implications and therapeutic opportunities. By consolidating the latest insights into iron metabolism in GBM, this review underscores its potential as a therapeutic target for improving patient care in combination with the standard of care approach.

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OBJECTIVES: This narrative review addresses relevant points about Chapare virus (CHAV) entry in oral cells, CHAV transmission, and preventive strategies in dental clinical settings. It is critical in dentistry due to the frequent presence of gingival hemorrhage occurred in CHAV-infected patients. MATERIALS AND METHODS: Studies related to CHAV were searched in MEDLINE/PubMed, Scopus, EMBASE, and Web-of-Science databases without language restriction or year of publication. RESULTS: Recently, the PAHO/WHO and CDC indicate a presence of human-to-human transmission of CHAV associated with direct contact with saliva, blood, or urine, and also through droplets or aerosols created in healthcare procedures. CHAV was detected in human oropharyngeal saliva and gingival bleeding was confirmed in all cases of CHAV hemorrhagic fever, including evidence of nosocomial CHAV transmission in healthcare workers. We revisited the human transferrin receptor 1 (TfR1) expression in oral, nasal, and salivary glands tissues, as well as, we firstly identified the critical residues in the pre-glycoprotein (GP) complex of CHAV that interacts with human TfR1 using cutting-edge in silico bioinformatics platforms associated with molecular dynamic analysis. CONCLUSIONS: In this multidisciplinary view, we also point out critical elements to provide perspectives on the preventive strategies for dentists and frontline healthcare workers against CHAV, and in the implementation of salivary diagnostic platforms for virus detection, which can be critical to an urgent plan to prevent human-to-human transmission based on current evidence. CLINICAL RELEVANCE: The preventive strategies in dental clinical settings are pivotal due to the aerosol-generating procedures in dentistry with infected patients or suspected cases of CHAV infection.

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Infectious bovine keratoconjunctivitis (IBK) is an ocular disease that affects bovines and has significant economic and health effects worldwide. Gram negative bacteria Moraxella bovis and Moraxella bovoculi are its main etiological agents. Antimicrobial therapy against IBK is often difficult in beef and dairy herds and, although vaccines are commercially available, their efficacy is variable and dependent on local strains. The aim of this study was to analyze for the first time the genomes of Uruguayan clinical isolates of M. bovis and M. bovoculi. The genomes were de novo assembled and annotated; the genetic basis of fimbrial synthesis was analyzed and virulence factors were identified. A 94% coverage in the reference genomes of both species, and more than 80% similarity to the reference genomes were observed. The mechanism of fimbrial phase variation in M. bovis was detected, and the tfpQ orientation of these genes confirmed, in an inversion region of approximately 2.18kb. No phase variation was determined in the fimbrial gene of M. bovoculi. When virulence factors were compared between strains, it was observed that fimbrial genes have 36.2% sequence similarity. In contrast, the TonB-dependent lactoferrin/transferrin receptor exhibited the highest percentage of amino acid similarity (97.7%) between strains, followed by cytotoxins MbxA/MbvA and the ferric uptake regulator. The role of these virulence factors in the pathogenesis of IBK and their potential as vaccine components should be explored.

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Fe-deficiency anaemia is a major public health concern in children under 5 years of age. TMPRSS6 gene, encoding matriptase-2 protein, is implicated in Fe homoeostasis and has been associated with anaemia and Fe status in various populations. The aim of this cross-sectional study was to investigate the associations between the single nucleotide polymorphism (SNP) TMPRSS6 rs855791 and biomarkers of anaemia and Fe deficiency in Brazilian children attending day care centres. A total of 163 children aged 6-42 months were evaluated. Socio-economic, demographic, biochemical, haematological, immunological and genotype data were collected. Multiple logistic and linear regressions with hierarchical selection were used to assess the effects of independent variables on categorised outcomes and blood marker concentrations. Minor allele (T) frequency of rs855791 was 0·399. Each copy of the T allele was associated with a 4·49-fold increased risk of developing anaemia (P = 0·005) and a 4·23-fold increased risk of Fe deficiency assessed by serum soluble transferrin receptor (sTfR) (P < 0·001). The dose of the T allele was associated with an increase of 0·18 mg/l in sTfR concentrations and reductions of 1·41 fl and 0·52 pg in mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), respectively. In conclusion, the T allele of SNP TMPRSS6 rs855791 was significantly associated with anaemia and Fe deficiency assessed by sTfR in Brazilian children attending day care centres. The effect was dose dependent, with each copy of the T allele being associated with lower MCV and MCH and higher concentrations of sTfR.

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Extracellular vesicles (EVs) are involved in diverse cellular functions, playing a significant role in cell-to-cell communication in both physiological conditions and pathological scenarios. Therefore, EVs represent a promising therapeutic strategy. Oligodendrocytes (OLs) are myelinating glial cells developed from oligodendrocyte progenitor cells (OPCs) and damaged in chronic demyelinating diseases such as multiple sclerosis (MS). Glycoprotein transferrin (Tf) plays a critical role in iron homeostasis and has pro-differentiating effects on OLs in vivo and in vitro. In the current work, we evaluated the use of EVs as transporters of Tf to the central nervous system (CNS) through the intranasal (IN) route. For the in vitro mechanistic studies, we used rat plasma EVs. Our results show that EVTf enter OPCs through clathrin-caveolae and cholesterol-rich lipid raft endocytic pathways, releasing the cargo and exerting a pro-maturation effect on OPCs. These effects were also observed in vivo using the animal model of demyelination induced by cuprizone (CPZ). In this model, IN administered Tf-loaded EVs isolated from mouse plasma reached the brain parenchyma, internalizing into OPCs, promoting their differentiation, and accelerating remyelination. Furthermore, in vivo experiments demonstrated that EVs protected the Tf cargo and significantly reduced the amount of Tf required to induce remyelination as compared to soluble Tf. Collectively, these findings unveil EVs as functional nanocarriers of Tf to induce remyelination.

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There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2-6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1-7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.

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Objective: This study investigated the factors associated with satisfactory early postoperative wound conditions. Method: A prospective study was conducted with patients (n=179) submitted to osteosynthesis in general, in a hospital orthopedics service. In the preoperative period, patients underwent laboratory exams and the surgical indications were based on the type of fracture and the patient's clinical conditions. In the postoperative period, patients were evaluated based on the presence of complications and considering their surgical wounds. Chi-square, Fisher, Mann-Whitney, and Kruskal-Wallis tests were used in the analysis. To identify the factors associated with wound condition, univariate and multiple logistic regression analysis was used. Results: In the univariate analysis, each transferring unit reduction increased the chance of satisfactory outcome by 1.1% (p=0.0306; OR= 0.989 (1.011); 95%CI= 0.978;0.999; 1.001;1.023). The presence of SAH increased 2.7 fold the chance of satisfactory outcome (p=0.0424; OR= 2,667; 95%CI= 1,034;6,877). Hip fracture increased 2.6 fold the chance of satisfactory outcome (p=0.0272; OR=2.593; IC95%=1.113; 6.039). And the absence of a compound fracture increased 5.5 fold the chance of satisfactory wound outcome (p=0.0004; OR=5,493; 95%CI=2,132;14,149). In the multiple analysis, patients with non compound fractures were 9.7 times more likely to experience a satisfactory outcome when compared to patients with compound fractures (p=0.0014; OR=9,687; 95%CI= 2,399; 39,125). Conclusion: There was an inverse relationship between plasma proteins levels and satisfactory surgical wounds outcome. Only exposure remained associated with wound conditions. Level Of Evidence: II, Prospective Study.

Objetivo: Este estudo investigou os fatores associados à condição satisfatória de ferida pós-operatória precoce. Método: Foi desenvolvido um estudo prospectivo com pacientes (n=179) submetidos a osteossínteses em geral, em um serviço de ortopedia hospitalar. No período pré-operatório os pacientes foram submetidos a exames laboratoriais e as indicações cirúrgicas foram baseadas no tipo de fratura e condições clínicas. No período pós-operatório, os pacientes foram avaliados conforme a presença de complicações e feridas operatórias. Foram utilizados na análise os testes Qui-quadrado, Fisher, Mann-Whitney, Kruskal-Wallis. Para identificar os fatores associados à condição da ferida, foi utilizada a análise de regressão logística univariada e múltipla. Resultados: Na análise univariada, cada unidade a menos de transferrina, aumentou a chance de condição satisfatória em 1.1% (p= 0.0306; OR= 0.989 (1.011); IC95%= 0.978;0.999; 1.001;1.023). A presença de HAS aumentou a chance de condição satisfatória em 2.7 vezes (p=0.0424; OR= 2.667; IC95%= 1.034;6.877). Fratura de quadril aumentou a chance de condição satisfatória em 2.6 vezes (p=0.0272; OR=2.593; IC95%=1.113;6.039). E não apresentar fratura exposta, aumentou a chance de condição satisfatória da ferida em 5.5 vezes (p=0.0004; OR=5.493; IC95%=2.132;14.149). Na análise múltipla, fraturas sem exposição, apresentaram chance 9.7 vezes maior de apresentar condição satisfatória do que insatisfatória; quando comparadas às que apresentaram exposição (p=0.0014; OR=9.687; IC95%= 2,399; 39.125). Conclusão: Houve uma relação inversa entre proteínas plasmáticas e presença de feridas operatórias satisfatórias. Apenas a exposição se manteve associada à condição da ferida. Nível de Evidência: II; Estudo Prospectivo.

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Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of such decorated nanoparticles leads to nonspecific interactions diverting them from their desired target. We report a simple two-step procedure for the preparation of biohybrid nanoparticles containing a core of hydrophobic quantum dots coated with a multilayer of human serum albumin. These nanoparticles were prepared by ultra-sonication, crosslinked using glutaraldehyde, and decorated with proteins such as human serum albumin or human transferrin in their native conformations. These nanoparticles were homogeneous in size (20-30 nm), retained the fluorescent properties of quantum dots, and did not show a "corona effect" in the presence of serum. The uptake of transferrin-decorated quantum dot nanoparticles was observed in A549 lung cancer and SH-SY5Y neuroblastoma cells but not in non-cancerous 16HB14o- or retinoic acid dopaminergic neurons differentiated SH-SY5Y cells. Furthermore, digitoxin-loaded transferrin-decorated nanoparticles decreased the number of A549 cells without effect on 16HB14o-. Finally, we analyzed the in vivo uptake of these biohybrids by murine retinal cells, demonstrating their capacity to selectively target and deliver into specific cell types with excellent traceability.

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AIM: We aimed to evaluate associations between serum ferritin and transferrin and variables related to the metabolic syndrome (MetS) in children. METHODS: Cross-sectional and longitudinal study in prepubertal children (n = 832) aged 3-14 years. A subset (n = 203) were re-examined after a mean follow-up of 3.7 ± 0.8 years[range 2-6]. Outcomes were MetS and MetS components scores, glycosylated haemoglobin (HbA1c), and their follow-up change. RESULTS: Children with low ferritin had increased HbA1c Z scores (ANCOVA, P = 0.003). Ferritin was inversely associated with glycaemia [fully adjusted ß (95% confidence interval): -2.35(-4.36 to -0.34)]. Transferrin was associated with diastolic blood pressure [ß: 0.02(0.01-0.04)] and log-HOMA-IR [ß:0.001(0.0005-0.002)]. MetS risk score worsened during follow-up in children with the lowest baseline ferritin levels. In contrast, at baseline ferritin was positively associated with all (except glycaemia) the MetS-related variables but adjustments for inflammatory, hepatic function, and body mass markers attenuated those associations (P > 0.05). CONCLUSIONS: Lower iron status was independently associated with glycaemic markers and MetS in children, whereas higher ferritin levels were related to other cardiometabolic risk markers under the influence of inflammation, hepatic injury and body mass. Research is required to study whether this mixed pattern is part of an early risk or would be explained by a normal transition during growth and development.

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Although transferrin (Tf) is a glycoprotein best known for its role in iron delivery, iron-independent functions have also been reported. Here, we assessed apoTf (aTf) treatment effects on Neuro-2a (N2a) cells, a mouse neuroblastoma cell line which, once differentiated, shares many properties with neurons, including process outgrowth, expression of selective neuronal markers, and electrical activity. We first examined the binding of Tf to its receptor (TfR) in our model and verified that, like neurons, N2a cells can internalize Tf from the culture medium. Next, studies on neuronal developmental parameters showed that Tf increases N2a survival through a decrease in apoptosis. Additionally, Tf accelerated the morphological development of N2a cells by promoting neurite outgrowth. These pro-differentiating effects were also observed in primary cultures of mouse cortical neurons treated with aTf, as neurons matured at a higher rate than controls and showed a decrease in the expression of early neuronal markers. Further experiments in iron-enriched and iron-deficient media showed that Tf preserved its pro-differentiation properties in N2a cells, with results hinting at a modulatory role for iron. Moreover, N2a-microglia co-cultures revealed an increase in IL-10 upon aTf treatment, which may be thought to favor N2a differentiation. Taken together, these findings suggest that Tf reduces cell death and favors the neuronal differentiation process, thus making Tf a promising candidate to be used in regenerative strategies for neurodegenerative diseases.

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IMPORTANCE: Since the beginning of the COVID-19 pandemic, numerous metabolic alterations have been observed in individuals with this disease. It is known that SARS-CoV-2 can mimic the action of hepcidin, altering intracellular iron metabolism, but gaps remain in the understanding of possible outcomes in other pathways involved in the iron cycle. OBJECTIVE: To profile iron, ferritin and hepcidin levels and transferrin receptor gene expression in patients diagnosed with COVID-19 between June 2020 and September 2020. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study that evaluated iron metabolism markers in 427 participants, 218 with COVID-19 and 209 without the disease. EXPOSURES: The primary exposure was positive diagnose to COVID-19 in general population of Santo André and São Bernardo cities. The positive and negative diagnose were determinate through RT-qPCR. MAIN OUTCOMES AND MEASURES: Devido a evidências de alterações do ciclo do ferro em pacientes diagnosticados com COVID-19 e devido a corregulação entre hepcidina e receptor de transferrina, uma análise da expressão gênica deste último, poderia trazer insights sobre o estado de ferro celular. A hipótese foi confirmada, mostrando aumento da expressão de receptor de transferrina concomitante com redução do nível de hepcidina circulante. RESULTS: Serum iron presented lower values in individuals diagnosed with COVID-19, whereas serum ferritin presented much higher values in infected patients. Elderly subjects had lower serum iron levels and higher ferritin levels, and men with COVID-19 had higher ferritin values than women. Serum hepcidin was lower in the COVID-19 patient group and transferrin receptor gene expression was higher in the infected patient group compared to controls. CONCLUSIONS AND RELEVANCE: COVID-19 causes changes in several iron cycle pathways, with iron and ferritin levels being markers that reflect the state and evolution of infection, as well as the prognosis of the disease. The increased expression of the transferrin receptor gene suggests increased iron internalization and the mimicry of hepcidin action by SARS-CoV-2, reduces iron export via ferroportin, which would explain the low circulating levels of iron by intracellular trapping.

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Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.

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ABSTRACT Objective This study investigated the factors associated with satisfactory early postoperative wound conditions. Method A prospective study was conducted with patients (n=179) submitted to osteosynthesis in general, in a hospital orthopedics service. In the preoperative period, patients underwent laboratory exams and the surgical indications were based on the type of fracture and the patient's clinical conditions. In the postoperative period, patients were evaluated based on the presence of complications and considering their surgical wounds. Chi-square, Fisher, Mann-Whitney, and Kruskal-Wallis tests were used in the analysis. To identify the factors associated with wound condition, univariate and multiple logistic regression analysis was used. Results In the univariate analysis, each transferring unit reduction increased the chance of satisfactory outcome by 1.1% (p=0.0306; OR= 0.989 (1.011); 95%CI= 0.978;0.999; 1.001;1.023). The presence of SAH increased 2.7 fold the chance of satisfactory outcome (p=0.0424; OR= 2,667; 95%CI= 1,034;6,877). Hip fracture increased 2.6 fold the chance of satisfactory outcome (p=0.0272; OR=2.593; IC95%=1.113; 6.039). And the absence of a compound fracture increased 5.5 fold the chance of satisfactory wound outcome (p=0.0004; OR=5,493; 95%CI=2,132;14,149). In the multiple analysis, patients with non compound fractures were 9.7 times more likely to experience a satisfactory outcome when compared to patients with compound fractures (p=0.0014; OR=9,687; 95%CI= 2,399; 39,125). Conclusion There was an inverse relationship between plasma proteins levels and satisfactory surgical wounds outcome. Only exposure remained associated with wound conditions. Level Of Evidence: II, Prospective Study.

RESUMO Objetivo Este estudo investigou os fatores associados à condição satisfatória de ferida pós-operatória precoce. Método Foi desenvolvido um estudo prospectivo com pacientes (n=179) submetidos a osteossínteses em geral, em um serviço de ortopedia hospitalar. No período pré-operatório os pacientes foram submetidos a exames laboratoriais e as indicações cirúrgicas foram baseadas no tipo de fratura e condições clínicas. No período pós-operatório, os pacientes foram avaliados conforme a presença de complicações e feridas operatórias. Foram utilizados na análise os testes Qui-quadrado, Fisher, Mann-Whitney, Kruskal-Wallis. Para identificar os fatores associados à condição da ferida, foi utilizada a análise de regressão logística univariada e múltipla. Resultados Na análise univariada, cada unidade a menos de transferrina, aumentou a chance de condição satisfatória em 1.1% (p= 0.0306; OR= 0.989 (1.011); IC95%= 0.978;0.999; 1.001;1.023). A presença de HAS aumentou a chance de condição satisfatória em 2.7 vezes (p=0.0424; OR= 2.667; IC95%= 1.034;6.877). Fratura de quadril aumentou a chance de condição satisfatória em 2.6 vezes (p=0.0272; OR=2.593; IC95%=1.113;6.039). E não apresentar fratura exposta, aumentou a chance de condição satisfatória da ferida em 5.5 vezes (p=0.0004; OR=5.493; IC95%=2.132;14.149). Na análise múltipla, fraturas sem exposição, apresentaram chance 9.7 vezes maior de apresentar condição satisfatória do que insatisfatória; quando comparadas às que apresentaram exposição (p=0.0014; OR=9.687; IC95%= 2,399; 39.125). Conclusão Houve uma relação inversa entre proteínas plasmáticas e presença de feridas operatórias satisfatórias. Apenas a exposição se manteve associada à condição da ferida. Nível de Evidência: II; Estudo Prospectivo.

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Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

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Lung cancer is, currently, one of the main malignancies causing deaths worldwide. To date, early prognostic and diagnostic markers for small cell lung cancer (SCLC) have not been systematically and clearly identified, so most patients receive standard treatment. In the present study, we combine quantitative proteomics studies and the use of magnetic core-shell nanoparticles (mCSNP's), first to identify a marker for lung cancer, and second to functionalize the nanoparticles and their possible application for early and timely diagnosis of this and other types of cancer. In the present study, we used label-free mass spectrometry in combination with an ion-mobility approach to identify 220 proteins with increased abundance in small cell lung cancer (SCLC) cell lines. Our attention was focused on cell receptors for their potential application as mCSNP's targets; in this work, we report the overexpression of Transferrin Receptor (TfR1) protein, also known as Cluster of Differentiation 71 (CD71) up to a 30-fold increase with respect to the control cell. The kinetics of endocytosis, evaluated by a flow cytometry methodology based on fluorescence quantification, demonstrated that receptors were properly activated with the transferrin supported on the magnetic core-shell nanoparticles. Our results are important in obtaining essential information for monitoring the disease and/or choosing better treatments, and this finding will pave the way for future synthesis of nanoparticles including chemotherapeutic drugs for lung cancer treatments.

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RESUMEN Fundamento un aspecto poco relacionado de la plasmaféresis productiva, es el efecto que puede causar sobre el hierro corporal en donantes regulares de plasma. Objetivo caracterizar el comportamiento del perfil férrico en donantes regulares de plasmaféresis. Métodos estudio descriptivo transversal, realizado con 115 donantes de plasma, registrados en el Banco Provincial de Sangre de Cienfuegos. En un periodo de dos años, se estudiaron las variables: sexo, edad, tiempo en el programa, intensidad de donaciones, sideremia, transferrina, capacidad e índice de saturación, mediciones básicas del hemograma y parámetros eritrocitarios. La información se extrajo de las historias clínicas y los informes de laboratorio. Resultados las mediciones del mineral prevalecieron dentro del rango normal. El 27,0 % de los donantes mostraron ferropenia, más frecuente entre las mujeres, los mayores de edad, aquellos que llevaban mayor tiempo en el programa y habían donado mayor número de veces. Más de la mitad de los individuos presentaron capacidad e índice de saturación patológicos, sugerente de hematopoyesis ferropénica. Los parámetros eritrocitarios fueron más sensibles al relacionar ferropenia latente, con predominio de mediciones patológicas de volumen corpuscular medio, hemoglobina corpuscular media e índice de distribución eritrocitario. Conclusión la deficiencia de hierro subclínica resultó más frecuente de lo esperado entre los donantes de plasmaféresis incluidos en el estudio.

ABSTRACT Background a little related aspect of productive plasmapheresis is the effect it can have on body iron in regular plasma donors. Objective to characterize the behavior of the iron profile in regular plasmapheresis donors. Methods cross-sectional descriptive study, carried out with 115 plasma donors, registered in the Provincial Blood Bank of Cienfuegos. In a period of two years, the studied variables were: sex, age, time in the program, intensity of donations, serum iron, transferrin, capacity and saturation index, basic measurements of the blood count and erythrocyte parameters. Information was extracted from medical records and laboratory reports. Results the mineral measurements prevailed within the normal range. 27.0% of the donors showed iron deficiency, more frequent among women, the elderly, those who had been in the program for a longer time and had donated more times. More than half of the individuals presented pathological capacity and saturation index, suggestive of iron deficiency hematopoiesis. The erythrocyte parameters were more sensitive when relating latent iron deficiency, with a predominance of pathological measurements of mean corpuscular volume, mean corpuscular hemoglobin and erythrocyte distribution index. Conclusion subclinical iron deficiency was more frequent than expected among the plasmapheresis donors included in the study.

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The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to build a protein-protein interactions network for subsequent network topology analysis. Importantly, Fe is a sensitive double-edged sword where two extremes of its nutritional status may have harmful effects on innate and adaptive immunity. We identified clearly connected important hubs that belong to two clusters: (i) presentation of peptide antigens to the immune system with the involvement of redox reactions of Fe, heme, and Fe trafficking/transport; and (ii) ubiquitination, endocytosis, and degradation processes of proteins related to Fe metabolism in immune cells (e.g., macrophages). The identified potential biomarkers were in agreement with the current experimental evidence, are included in several immunological/biomarkers databases, and/or are emerging genetic markers for different stressful conditions. Although further validation is warranted, this hybrid method (human-machine collaboration) to extract meaningful biological applications using available data in literature and bioinformatics tools should be highlighted.

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Body iron excess appears to be related to insulin resistance and cardiometabolic risk and increased oxidative stress might be involved in this relationship. Very few studies have described the association between soluble transferrin receptor (sTfR) levels and cardiometabolic risk in the general population or antioxidant status. There were 239 subjects (20−65 years old) included in this cross-sectional study. Linear regressions adjusting for BMI, menopausal status, insulin resistance (HOMA-IR), physical inactivity, alcohol intake and subclinical/chronic inflammation were used to describe the association between sTfR, total antioxidant capacity (TAC), and measures of cardio-metabolic risk. sTfR levels were positively associated with TAC in men (ßeta [95% confidence interval ]: 0.31 [0.14 to 0.48]) and women (ßeta = 0.24 [0.07 to 0.40]) in non-adjusted and adjusted models (p < 0.05). In men, sTfR levels were inversely associated with waist circumference (ßeta [95% confidence interval]: −1.12 [−2.30 to −0.22]) and fasting glucose (−2.7 (−4.82 to −0.57), and positively with LDL cholesterol (12.41 (6.08 to 18.57) before and after adjustments for confounding variables. LDL cholesterol had a significant and positive association with TAC in non-adjusted and adjusted models in men (p < 0.05). sTfR levels are significantly associated with antioxidant status and a few specific cardio-metabolic risk variables, independently of covariates that included serum ferritin and hepcidin. This might imply that iron biomarkers in regard to cardiometabolic risk reflect physiological contexts other than iron metabolism.

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Phytochelators have been studied as templates for designing new drugs for chelation therapy. This work evaluated key chemical and biological properties of five candidate phytochelators for iron overload diseases: maltol, mimosine, morin, tropolone, and esculetin. Intra- and extracellular iron affinity and antioxidant activity, as well as the ability to scavenge iron from holo-transferrin, were studied in physiologically relevant settings. Tropolone and mimosine (and, to a lesser extent, maltol) presented good binding capacity for iron, removing it from calcein, a high-affinity fluorescent probe. Tropolone and mimosine arrested iron-mediated oxidation of ascorbate with the same efficiency as the standard iron chelator DFO. Also, both were cell permeant and able to access labile pools of iron in HeLa and HepG2 cells. Mimosine was an effective antioxidant in cells stressed by iron and peroxide, being as efficient as the cell-permeant iron chelator deferiprone. These results reinforce the potential of those molecules, especially mimosine, as adjuvants in treatments for iron overload.

Assuntos

RESUMO

AIM: To investigate the association between increased serum markers of iron (ferritin and transferrin saturation) and the severity and extent of periodontitis in post-menopausal (PM) women. MATERIALS AND METHODS: Data from 982 PM women participating in NHANES III were analysed. Exposures were high ferritin (≥300 µg/ml) and transferrin saturation (≥45%). The primary outcome was moderate/severe periodontitis defined according to Centers for Disease Control and Prevention and the American Academy of Periodontology. The extent of periodontitis was also assessed as outcome: proportion of sites affected by clinical attachment loss ≥4 mm and probing depth ≥4 mm. Crude and adjusted prevalence ratio (PR) and mean ratio (MR) were estimated using Poisson regression. RESULTS: The prevalence of moderate/severe periodontitis was 27.56%. High ferritin was associated with moderate/severe periodontitis in the crude (PR 1.55, p = .018) and in the final adjusted model (PR 1.53, p = .008). High ferritin and transferrin saturation levels were associated with a higher proportion of sites with clinical attachment loss ≥4 mm (p < .05). CONCLUSIONS: The increasing serum iron markers seem to contribute to periodontitis severity and extent in PM women.

Assuntos