Search

Aim: Out-of-hospital cardiac arrest (OHCA) is a major health concern in Western societies. Poor outcome after OHCA is determined by the extent of hypoxic-ischemic encephalopathy (HIE). Dysregulation of iron metabolism has prognostic relevance in patients with ischemic stroke and sepsis. The aim of this study was to determine whether serum iron parameters help to estimate outcomes after OHCA. Methods: In this prospective single-center study, 70 adult OHCA patients were analyzed. Serum ferritin, iron, transferrin (TRF), and TRF saturation (TRFS) were measured in blood samples drawn on day 0 (admission), day 2, day 4, and 6 months after the return of spontaneous circulation (ROSC). The association of 4 iron parameters with in-hospital mortality, neurological outcome (cerebral performance category [CPC]), and HIE was investigated by receiver operating characteristics and multivariate regression analyses. Results: OHCA subjects displayed significantly increased serum ferritin levels on day 0 and lowered iron, TRF, and TRFS on days 2 and 4 after ROSC, as compared to concentrations measured at a 6-month follow-up. Iron parameters were not associated with in-hospital mortality or neurological outcomes according to the CPC. Ferritin on admission was an independent predictor of features of HIE on cranial computed tomography and death due to HIE. Conclusion: OHCA is associated with alterations in iron metabolism that persist for several days after ROSC. Ferritin on admission can help to predict HIE. [ABSTRACT FROM AUTHOR]

There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. The aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). An 8-week double-blind randomized controlled trial was conducted. A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. Subjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by.4] vs Δ –1.3 [10.7] nmol/L; P =.001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P =.048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. Our study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations. [ABSTRACT FROM AUTHOR]

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and β-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker β-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ −2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2–86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96–2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia. Graphical Abstract Lay Summary: Bone quantity and quality are likely to be affected in patients with thalassemia who are dependent on regular blood transfusions. This study evaluated bone health in adults with transfusion-dependent thalassemia (TDT) by comparing bone density and microarchitecture with age- and BMI-matched controls. Adults with TDT had significantly lower bone mineral density (both areal and volumetric), suggesting low bone quantity compared to healthy controls. Trabecular and cortical microarchitecture were also adversely affected, suggesting impaired bone quality. Overall, the study highlights that adults with TDT have significantly compromised bone quantity and quality, increasing their risk for osteoporosis and related fractures. [ABSTRACT FROM AUTHOR]

Background: Sudanese children with End-Stage Kidney Disease (ESKD) often show limited improvement in hemoglobin levels despite treatment with recombinant human erythropoietin (rHuEPO). This study aims to assess the response to rHuEPO therapy by analyzing β-globin mRNA expression and reticulocyte parameters. Additionally, it classifies anemia among Sudanese pediatric patients based on iron status, considering age and gender as biological markers for evaluating treatment response. Methods: A prospective observational cohort study was conducted from January 2019 to February 2020 in Khartoum, Sudan, involving 45 anemic children aged 2 to 15 years diagnosed with ESKD. The treatment protocol included rHuEPO injections and maintenance hemodialysis. Laboratory assessments consisted of complete blood count (CBC), absolute reticulocyte count, ferritin, and transferrin measurements. β-globin mRNA expression was quantified using reverse transcription polymerase chain reaction (RT-PCR), and reticulocyte parameters, including Reticulocyte Hemoglobin Content (CHr), percentage of hypochromic reticulocytes (HYPO%), and Immature Reticulocyte Fraction (IRF), were measured via flow cytometry. Results: Significant variations in hemoglobin levels were observed across different age groups (p = 0.011). Gender analysis revealed a significant association with IRF, showing a lower IRF in male patients (p = 0.017). However, there were no significant differences in hemoglobin levels between genders (p = 0.999). β-globin mRNA expression showed considerable variability, with a strong positive correlation with hemoglobin levels (r = 0.875, p < 0.0001). Conclusion: Age and gender significantly influence treatment responses in children with ESKD, highlighting the need to consider growth physiology in anemia management. This study underscores the variability in β-globin mRNA expression and its association with Flow Cytometry parameters, demonstrating their effectiveness in evaluating iron status and guiding rHuEPO dosage. [ABSTRACT FROM AUTHOR]

During the last years, there has been an increasing research interest in the analysis of biological fluids requiring non-invasive sampling for biomedical and clinical applications. In this work, we have focused on the nasal exudate with the aim of investigating the potential use of this fluid to know the role of iron in stroke and also for diagnosis. Potential differences in the nasal exudate, collected in swabs, from diagnosed hemorrhagic stroke, ischemic stroke, and control groups were investigated with regard to total iron by inductively coupled plasma-mass spectrometry, iron fractionation studies by size exclusion chromatography together with post-column isotope dilution analysis, and four proteins containing iron (ferritin, transferrin, lactoferrin, and ferroportin) with ELISA kits. All these analyses represent an analytical challenge, considering the rather limited amount of sample (10–40 mg) available, being the nasal exudate extracted from the swab with 300 µL 10 mM Tris/HCl, pH = 7.4. Studies to obtain reliable analytical information, such as the blank contribution of the sampling step, evaluation of the extraction efficiency of the nasal exudate from the swab, and normalization strategies for data treatment, have been carried out. Results showed that despite the limited number of investigated samples, fractionation studies as well as the concentrations of ferritin and ferroportin obtained with ELISA kits showed a differential behavior between the different cohorts. [ABSTRACT FROM AUTHOR]

Background: Inflammatory markers were found to be elevated in patients with coronavirus disease (COVID-19). C-reactive protein (CRP), serum ferritin, and D-dimer levels may predict morbidity and mortality in (COVID-19) patients. Radiology plays a key role in the diagnosis, management, and follow-up of this disease. This study aimed to describe the radiological features of (COVID-19) infection, measure C-reactive protein (CRP), D-dimer, and ferritin levels and to correlate them with patient's outcome and to consider them as predictors of morbidity and mortality in (COVID-19) patients. Methods: This prospective cross-sectional analytic study had been done on 159 patients aged ≥ 18 years old, admitted at Assiut University Hospital RICU from November 2021 to November 2022, diagnosed as COVID-19 by positive RT-PCR. All patients were categorized on bases of HRCT chest disease reporting and data system (CO-RADS) scoring system into non-severe (CO-RADS 1,2,3) and severe (CO-RADS 4,5) groups. Inflammatory markers such as CRP, ferritin, and D-dimer were measured. Age, sex, comorbidities, need to mechanical ventilation MV, and mortality rate were reported. Correlation between HRCT(CO-RADS) score, inflammatory markers, and patient's outcome was assessed. Results: Higher CRP and serum ferritin levels, lower lymphocytic count, and higher frequency of need for mechanical ventilation were significantly greater in the severe group (P < 0.0001). Predictors of morbidity and mortality were CRP ≥ 133 mg/dl, DM, presence of chronic chest disease (P < 0.0001). A higher mortality rate was in patients of the severe group (65%) versus (9%) in the non-severe group (P < 0.0001). Conclusions: HRCT scan and measurement of CRP and ferritin plasma levels can be considered significant predictors for future prognosis and can early identify patients at risk of death and need for MV. Male gender, presence of DM, and chronic chest diseases are risk factors for severe illness. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia is a significant global health concern, diagnosed by measuring hemoglobin concentrations in combination with plasma ferritin concentration. This study investigated the variability in ferritin reference intervals among laboratories in the Netherlands and examined how this affects the identification of iron-related disorders.Ferritin reference intervals from 52 Dutch ISO15189-certified medical laboratories were collected. Ferritin, hemoglobin and mean corpuscular volume data of non-anemic apparently healthy primary care patients, measured by four laboratory platforms (Beckman, Abbott, Siemens, and Roche), were collected (n=397,548). Median ferritin levels were determined per platform, stratified by sex and age. The proportion of ferritin measurements outside of the reference interval was calculated using the reference intervals from the 52 laboratories (using a total of n=1,093,442 ferritin measurements). Lastly, ferritin data from 3,699 patients as captured in general practitioner (GP) data from the PHARMO Data Network were used to assess the variation of abnormal ferritin measurements per GP.Median plasma ferritin concentrations were approximately four times higher in men and twice as high in postmenopausal women compared to premenopausal women. Moreover, there are substantial differences in the median plasma ferritin concentration between the four platforms. However, even among laboratories using the same platform, ferritin reference intervals differ widely. This leads to significant differences in the percentages of measurements classified as abnormal, with the percentage of ferritin measurements below the reference limit in premenopausal women ranging from 11 to 53 %, in postmenopausal women from 3 to 37 %, and in men from 2 to 19 %. The percentage of ferritin measurements above the reference limit in premenopausal women ranged from 0.2 to 11 %, in postmenopausal women from 3 to 36 % and in men from 7 to 32 %.The lack of harmonization in ferritin measurement and the disagreement in plasma ferritin reference intervals significantly impact the interpretation of the iron status of patients and thereby the number of iron disorder diagnoses made. Standardization or harmonization of the ferritin assays and establishing uniform reference intervals and medical decision limits are essential to reduce the substantial variability in clinical interpretations of ferritin results. [ABSTRACT FROM AUTHOR]

Background: Gallstones are a common digestive disorder that threatens human health. Iron deficiency may be related to the formation of gallstones, but there is limited current epidemiological research. The objective of this study was to investigate the relationship between iron status and gallstones. Methods: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Gallstones were determined by using the 2007–2010 NHANES questionnaire. Multivariate linear regression models were used to examine the association between serum iron, serum ferritin and iron intake with the risk for gallstones. Subgroup analysis based on gender, age, race, and diabetes were performed. Fitted smoothing curves were used to describe the linear relationship. Results: The research involved 7847 participants aged 20 and above, among whom 845 were identified as having gallstones. Participants with higher serum iron levels tended to have a lower gallstones prevalence. A negative relationship between serum iron and gallstones prevalence was observed (OR = 0.979, 95% CI:0.965–0.992). The group with the highest serum iron tertile had a 23.7% lower risk of gallstones compared to the lowest tertile (OR = 0.763, 95% CI:0.628‒0.929). Gallstone prevalence was inversely correlated with iron intake in model 1. The negative association between serum iron and gallstones remained stable in stratifications, including gender, age, race, and diabetes. Conclusions: Elevated serum iron was associated with a decreased prevalence of gallstones. However, to confirm the impact of long-term iron metabolism on gallstone formation, additional prospective research is necessary. [ABSTRACT FROM AUTHOR]

Recent advances in mass spectrometry have indicated that the water-soluble antioxidant vitamin C differentially modulates the abundance of various proteins in the hepatic tissue of female and male mice. In this study, we performed LC-MS/MS to identify and quantify proteins that correlate with serum vitamin C concentrations in the whole brain, heart, liver, and spleen tissues in mice deficient for the enzyme L-Gulonolactone oxidase required for vitamin C synthesis in mammals. This work shows for the first time that various biological processes affected by a vitamin C deficiency are not only sex specific dependent but also tissue specific dependent even though many proteins have been identified and quantified in more than three organs. For example, the abundance of several complex III subunits of the mitochondrial electron transport chain correlated positively with the levels of serum vitamin C only in the liver and not in the other tissues examined in this study even though such proteins were identified in all the organs analyzed. Western blot analyses on the Uqcrc1 and Uqcrfs1 complex III subunits validated the mass spectrometry results. Interestingly, the ferritin subunits represented the few quantified protein complexes that correlated positively with serum vitamin C in all the organs examined. Concomitantly, serum ferritin light chain 1 was inversely correlated with vitamin C levels in the serum. Thus, our study provides an initial comprehensive atlas of proteins significantly correlating with vitamin C in four organs in mice that will be a useful resource to the scientific community. [ABSTRACT FROM AUTHOR]

In recent years, gene therapy has emerged as a promising strategy for combating tumors. However, the inherent instability and lack of specificity of gene delivery systems pose significant challenges. To address these limitations, we propose the development of a stable, efficient, and low-toxicity delivery nanoplatform with specific targeting capabilities. Here, we utilize the ferritin cage, known for its inherent ability to target transferrin receptor 1 (TfR1), as a nanocarrier for gene delivery. Through genetic engineering and chemical coupling methods, we modified the surface of ferritin with a cell-penetrating peptide (L17E) to enhance its cellular entry, resulting in the creation of Fn-L17E. This nanoplatform demonstrates improved physiological stability compared to wild-type ferritin (Fn). Furthermore, Fn-L17E loaded with BCL-2 siRNA exhibits enhanced silencing efficiency against BCL-2, a crucial antiapoptotic protein, in both A549 and HeLa cells, indicating its potential as an effective targeted gene delivery system for antitumor therapy. [ABSTRACT FROM AUTHOR]

Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (GDIII) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases. The study by Fu and colleagues presents a ferritin-adaptor platform for vaccine development, featuring a rabies virus vaccine candidate that enhances antigen stability and provides potent, durable protection after a single-dose administration. [ABSTRACT FROM AUTHOR]

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults. Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011–2013. Anemia was defined by hemoglobin concentrations <12 g/dL in women and <13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index. Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to cardiovascular disease (CVD), 302 to cancer, and 132 to respiratory disease. Compared to those with normal hemoglobin, participants with anemia had a higher risk of all-cause mortality (hazard ratio 1.81 [95% CI: 1.60–2.06]), and mortality due to CVD (1.77 [1.41–2.22]), cancer (1.81 [1.41–2.33]), and respiratory disease (1.72 [1.18–2.52]) in demographics-adjusted models. In fully adjusted models, associations with all-cause mortality (1.37 [1.19–1.58]) and cause-specific mortality were attenuated. In non-anemic participants, lower ferritin levels were not associated with all-cause or cause-specific mortality, though associations were observed among participants with lesser evidence of inflammation (CRP below the median level of 1.9 mg/L) and for cancer mortality in men only. Conclusion: Anemia is common among older adults and is associated with all-cause mortality, as well as mortality due to CVD, cancer, and respiratory disease. Our results do not provide evidence that iron deficiency, independent of anemia, is associated with mortality in this population. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)–confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: The COVID-19 pandemic has posed significant challenges, particularly for individuals residing in psychiatric facilities. This study aims to investigate the impact of COVID-19 on psychiatric patients, focusing on factors such as their vaccination status, comorbidities, medication regimens, and biomarkers like C-reactive protein (CRP) and ferritin. Methods: This retrospective study analyzed 100 patients with confirmed SARS-CoV-2 infections admitted to the private psychiatric clinic "Asclepius of Upper Volos" from March 2020 to March 2023. The data collected included sociodemographic characteristics, vaccination status, symptom severity, medication regimens, and levels of CRP and ferritin. Statistical analyses using IBM SPSS Statistics version 29 included Pearson's chi-square tests, Student's t-tests, and a survival time analysis via the log-rank test to assess associations between clinical characteristics and outcomes. Results: Among the participants, 64% were female and 74% received two doses of the COVID-19 vaccine. The majority experienced mild symptoms, with a survival rate of 74%. Statistically significant findings include a higher survival rate among vaccinated individuals (98.6%) versus unvaccinated individuals (1.4%, p < 0.001). Comorbidities like chronic obstructive pulmonary disease (COPD), coronary artery disease, and renal failure were associated with severe symptoms and higher mortality rates. Higher ferritin levels were significantly associated with poorer outcomes, with survivors having a mean ferritin level of 246.2 (SD = 150.3) compared to the 416.9 (SD = 215.9) seen in non-survivors (p < 0.001). Similarly, mean CRP levels were lower in survivors (1.58, SD = 1.96) than in non-survivors (3.46, SD = 2.92), with a p-value of 0.002. Conclusions: The findings underscore the importance of tailored health protocols and continued support for this vulnerable population. Enhanced strategies for managing comorbidities and utilizing biomarkers can aid in better predicting and improving psychiatric patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: Hemoglobin A1c (HbA1c), a key indicator of glycemic status over the last 3 months, is increasingly favored by clinicians to diagnose diabetes. Iron deficiency anemia (IDA), the most prevalent anemia worldwide, may alter HbA1c levels. However, data from eastern India are scarce, and existing studies offer conflicting results. This study aimed to investigate the impact of IDA on HbA1c levels in nondiabetics and to explore the correlation of HbA1c with hemoglobin (Hb), parameters of the iron profile, and red blood cell (RBC) indices. Methods: This cross-sectional analytical study compared 60 euglycemic patients with IDA, aged 18 to 60, to 60 age- and sex-matched euglycemic individuals without anemia. Data analysis was performed using SPSS version 25, with significance set at P < .05. Spearman's rho correlation coefficients examined correlations between Hb, serum iron, serum ferritin, total iron binding capacity (TIBC), transferrin saturation, packed cell volume (PCV), reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) with HbA1c. Multinomial logistic regression analyzed the relationships of HbA1c (dependent variable) with RBC indices and iron profile parameters (independent variables). Results: The mean (SD) HbA1c value for IDA patients was 6.5 (0.5)% compared to 5.13 (0.80)% for controls (P < .001). HbA1c showed significant negative correlations with Hb, PCV, serum iron, serum ferritin, transferrin saturation, MCV, MCH, and MCHC, while TIBC was positively correlated with HbA1c. Each unit decrease in Hb increased the likelihood of HbA1c values in the prediabetic and diabetic range by 2.61 times (95% CI = 1.65-3.50) and 2.40 times (95% CI = 1.81-3.77), respectively (P < 0.001). Conclusion: The study highlights a significant increase in HbA1c levels with the worsening of IDA in non-diabetics, indicating that IDA should be addressed before interpreting HbA1c results accurately. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+. Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe2+, and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe2+, and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD. Methods: 3169 patients were enrolled in the "UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study". We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium). Results: 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p<0.0001). Logistic regression showed good sensitivity (69.4%) and specificity (80.4%) selecting the variables FER and KL-6 concentrations, age and gender-male correlated with a diagnosis of idiopathic ILD. Conclusion: Our study showed the excellent diagnostic value of KL-6 for detecting ILD, which irrespective of the final diagnosis and extent of disease, is always elevated and is a reliable biomarker of lung fibrosis in various diseases, ranging from idiopathic to autoimmune forms. Our study proposed an ILD differentiation model including clinical background. In this context, combination of serum markers and clinical data, as seen in our cohort, may lead to a further improvement in diagnostic accuracy for ILD. [ABSTRACT FROM AUTHOR]

Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200 mg of bovine lactoferrin (bLf) once (n = 14) or twice (n = 3) a day before meals. The patients, treated with 200 mg/day of bLf, exhibited a significant increase in red blood cells (+10%, p < 0.001), hemoglobin (+4%, p < 0.001), and hematocrit (+15%, p = 0.004), accompanied by a significant reduction in serum Ftn levels (−52%, p < 0.001), C-reactive protein (CRP) (−85.0%, p < 0.001), and D-dimers (−19%, p < 0.001). Among the three patients treated with 400 mg/day of bLf, two had effects similar to those of patients bLf-treated with 200 mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from −97% to −75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender (p = 0.78), age (p = 0.66), baseline symptoms (p = 0.20), and concomitant acute (p = 0.34) and chronic (p = 0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia–reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia. Methods: A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen–glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis. Results: In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe2+ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline. Conclusion: Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI. [ABSTRACT FROM AUTHOR]

Purpose: Transfusion-dependent thalassemia (TDT) is associated with iron accumulation in the body and an increased tendency for thrombosis. With the increased life expectancy in these patients, the detection of neurocognitive complications has gained importance. This study investigates the microstructural changes in TDT patients using advanced diffusion MRI techniques and their relationship with laboratory parameters. Methods: The study included 14 TDT patients and 14 control subjects. Tract-based spatial statistics (TBSS) were used to examine differences in DTI parameters such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in thalassemia patients using multi-shell DWI images. The mean kurtosis (MK) difference was investigated using diffusion kurtosis imaging. Fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) differences were examined using fixel-based analysis. In the patient group, correlative tractography was used to investigate the relationship between DTI parameters and platelet (PLT) and ferritin levels. Results: Increase in RD and MD was observed, particularly in the white matter tracts of the corona radiata in patient group. Additionally, an increase in AD was detected in a limited area. Correlative tractography in thalasemia patients showed a positive correlation between increases in RD, MD, and AD with PLT and ferritin. Fixel-based analysis demonstrated a dispersed distribution in white matter fibers, with a more pronounced decrease in FD, FC, and FDC in the internal capsule. Conclusion: There is widespread involvement in the white matter and fiber tracts in thalassemia patients, which is highly correlated with thrombotic parameters. [ABSTRACT FROM AUTHOR]

Aurothiomalate (AuTM) is an FDA‐approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP‐OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provided a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR‐metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug. [ABSTRACT FROM AUTHOR]

For the detection of ferritin, this work engineered an electrochemical immunosensor by functionalizing multi-walled carbon nanotubes (MWCNTs) and integrating them into a screen-printed carbon electrode (SPCE) platform. Under optimal conditions (pH 7.4, antibody concentration 10 μg/mL, incubation time 30 min), the developed immunosensor exhibited a linear relationship between the electrochemical signal and ferritin concentrations spanning 1–500 ng/mL. Notably, it demonstrated an impressive ability to detect ferritin at exceptionally low levels, with a limit of detection reaching 0.3 ng/mL. The immunosensor demonstrated high selectivity, good reproducibility (RSD = 3.2 %, n = 5), and stability (87.3 % of initial response after 14 days at 4°C). The immunosensor was used to sensing ferritin in serum and good agreement with the commercial ELISA method (relative error < 5 %). The proposed sensor shows promise as a analytical approach for early diagnosis of lymphoma and point-of-care testing. [ABSTRACT FROM AUTHOR]

Viral infections in animals continue to pose a significant challenge, affecting livestock health, welfare, and food safety, and, in the case of zoonotic viruses, threatening global public health. The control of viral diseases currently relies on conventional approaches such as inactivated or attenuated vaccines produced via platforms with inherent limitations. Self-assembling ferritin nanocages represent a novel vaccine platform that has been utilized for several viruses, some of which are currently undergoing human clinical trials. Experimental evidence also supports the potential of this platform for developing commercial vaccines for veterinary viruses. In addition to improved stability and immunogenicity, ferritin-based vaccines are safe and DIVA-compatible, and can be rapidly deployed in response to emerging epidemics or pandemics. This review discusses the structural and functional properties of ferritin proteins, followed by an overview of the design and production of ferritin-based vaccines, the mechanisms of immune responses, and their applications in developing vaccines against animal and zoonotic viruses. [ABSTRACT FROM AUTHOR]

Ferritin is a naturally occurring iron storage protein. Leguminous ferritins exhibit unique structural features, including diverse subunit composition and an extension peptide, which contribute to superior thermal stability compared to animal ferritins. The high iron content, remarkable effectiveness, low risk of oxidative damage and thermal stability make the leguminous ferritin an attractive candidate for iron supplementation. Moreover, apoferritin is an excellent nanosized carrier for encapsulating bioactive compounds due to its inherent inner cavity, water solubility, biocompatibility, and reversible self‐assembly behavior. However, the harsh condition during encapsulation by unmodified ferritins may cause damage to sensitive bioactive compounds. Thus, different processing methods are employed to alter the leguminous ferritin structures, including chemical, enzymatic, mild heat treatments, and nonthermal processing to achieve gentler encapsulation conditions for a wide range of bioactive compounds. Another challenge is to improve the stability of leguminous ferritin to withstand gastric digestion. The degradation of ferritin by proteases may lead to premature release of bioactive compounds. Recent works demonstrated that certain phenolic compounds such as proanthocyanidin‐induced protein association, thereby enhancing digestive stability of ferritins, leading to a sustained release and a potentially greater bioavailability of bioactive compounds. Leguminous ferritin also has the potential to serve as a stabilizer for the Pickering emulsion, where the hydrophilic and hydrophobic compounds can be encapsulated in the ferritin nanocages and oil phase, respectively. The release and absorption of bioactive compounds in encapsulates and emulsions will need to be further demonstrated through in vivo studies. [ABSTRACT FROM AUTHOR]

In the recent history of the SARS-CoV-2 outbreak, vaccines have been a crucial public health tool, playing a significant role in effectively preventing infections. However, improving the efficacy while minimizing side effects remains a major challenge. In recent years, there has been growing interest in nanoparticle-based delivery systems aimed at improving antigen delivery efficiency and immunogenicity. Among these, self-assembled nanoparticles with varying sizes, shapes, and surface properties have garnered considerable attention. This paper reviews the latest advancements in the design and development of SARS-CoV-2 vaccines utilizing self-assembled materials, highlighting their advantages in delivering viral immunogens. In addition, we briefly discuss strategies for designing a broad-spectrum universal vaccine, which provides insights and ideas for dealing with possible future infectious sarbecoviruses. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia is a prevalent form of anemia, particularly among women. Diagnosing and tracking this condition typically requires various measurements of serum iron, ferritin, and total iron-binding capacity (TIBC) through blood testing. Objectives: This study aims to evaluate the utility of saliva as a predictive marker for monitoring iron levels in iron deficiency anemia by comparing and correlating iron, ferritin, and TIBC levels in the serum and saliva of anemic and healthy women. Methods: In this comparative analysis, 40 women aged 20 - 40 with a similar periodontal status (anemic subjects = 20 and healthy subjects = 20) were examined. After a complete hematological and oral examination, salivary samples were collected using the spitting method, and iron, ferritin, and TIBC levels were measured and compared to the serum levels. Data were analyzed using SPSS 24. Results: The study results showed that the differences in saliva iron and ferritin levels were insignificant between the two groups (P-value = 0.07 and 0.26, respectively), but those were statistically significant in the serum (P-value = 0.0001 and 0.0001, respectively). Additionally, a significant difference was found in the saliva TIBC level (P-value = 0.001), which was negligible in the serum (P-value = 0.118). Conclusions: The results underscore the efficacy of integrating both serum and saliva analyses for comprehending iron-related parameters. While saliva analysis cannot entirely substitute for serum analysis, it represents a convenient approach that may serve as an initial step or be employed in large-scale anemia screenings. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AbstractObjectivesMaterials and methodsResultsConclusion\nSHORT CONDENSATIONTo evaluate improvements in laboratory markers of anaemia (haemoglobin, haematocrit, serum iron, and ferritin) in women with subjective heavy menstrual bleeding (HMB) treated with the levonorgestrel 19.5-mg intrauterine device.We conducted a pilot study at the Department of Obstetrics and Gynaecology, University of Campinas, Faculty of Medical Sciences, Campinas, SP, Brazil. We compared anaemia markers in 73 women aged 18–48 years suffering from HMB, one year after placement of the IUD.The mean age of participants was 30.0 years (range 24–38); more than half were white, and the mean body mass index (kg/m2) was 27.0. Twenty (27.4%) participants exited the study due to loss to follow-up (n = 12; 16.4%), expulsion (n = 7; 9.6%) and uterine perforation (n = 1; 1.4%). One-year post-IUD placement, amenorrhoea was reported by 10 (13.7%) women. According to intention-to-treat and per protocol analyses, the proportion of women with normal haemoglobin levels significantly improved (p = 0.014 in both analyses), as did haematocrit (p < 0.001 in both analyses) and serum iron (p = 0.003 in both analyses) compared to baseline evaluations. The proportion of women with normal ferritin levels also improved (p < 0.001) in both analyses using a cut-off of 15 ng/ml, though no significant difference was observed using a 30 ng/ml cut-off (p = 0.083 in both analyses).The levonorgestrel 19.5-mg IUD effectively improved laboratory markers of anaemia one year after placement in women with HMB.Our results show that the levonorgestrel 19.5-mg IUD significantly improved anaemia markers in subjects with subjective HMB one year after insertion. The occurrence of expulsions emerged as a notable concern in this treatment group. [ABSTRACT FROM AUTHOR]

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (all p < 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (all p < 0.01), and between PLR and ESR and ferritin levels (p < 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (all p < 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Iron plays vital roles in important biological processes in fish, but can be toxic in high concentrations. The information on metalloproteins that participate in maintenance of Fe homeostasis in an esocid fish, the northern pike, as an important freshwater bioindicator species, are rather scarce. The aim of this study was to identify main cytosolic constituents that sequester Fe in the northern pike liver. The method applied consisted of two-dimensional HPLC separation of Fe-binding biomolecules, based on anion-exchange followed by size-exclusion fractionation. Apparent molecular masses of two main Fe-metalloproteins isolated by this procedure were ~360 kDa and ~50 kDa, with the former having more acidic pI, and indicated presence of ferritin and hemoglobin, respectively. MALDI-TOF-MS provided confirmation of ferritin subunit with a m/z peak at 20.65 kDa, and hemoglobin with spectra containing main m/z peak at 16.1 kDa, and smaller peaks at 32.1, 48.2, and 7.95 kDa (single-charged Hb-monomer, dimer, and trimer, and double-charged monomer, respectively). LC-MS/MS with subsequent MASCOT database search confirmed the presence of Hb-β subunits and pointed to close relation between esocid and salmonid fishes. Further efforts should be directed towards optimization of the conditions for metalloprotein analysis by mass spectrometry, to extend the knowledge on intracellular metal-handling mechanisms. [ABSTRACT FROM AUTHOR]

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions Minimal evidence exists regarding faecal immunochemical tests (FITs) for colorectal cancer (CRC) site, stage and grade in symptomatic patients. The primary aim is to determine any association between faecal haemoglobin concentration (f‐Hb) (analysed with OC‐Sensor™ Pledia) and these prognostic factors. The secondary aim is to determine the association between f‐Hb and anaemia, microcytosis and iron deficiency (Hb, mean corpuscular volume [MCV] and ferritin).Symptomatic 2‐week wait CRC patients with FIT were included (July 2019–October 2022). Median f‐Hb and interquartile range according to sex, stage, grade and site (right‐sided, caecum to transverse colon, R‐CRC; left‐sided, splenic flexure to rectum, L‐CRC) were compared using the Mann–Whitney U test. Hb, MCV and ferritin were categorized into two groups and the median f‐Hb was compared using the Mann–Whitney U test.In all, 114 patients (57 women, 57 men) were studied; 46 had R‐CRC (f‐Hb = 113 μg Hb/g) and 68 had L‐CRC (f‐Hb = 342 μg Hb/g) (P = 0.07). Sixty‐nine were moderately differentiated CRC (f‐Hb = 183 μg Hb/g) and 29 were poorly differentiated (f‐Hb = 866 μg Hb/g) (P = 0.04). By T‐stage, 35 were early (T1/2) (f‐Hb = 170 μg Hb/g) and 79 were advanced (T3/4) (f‐Hb = 200 μg Hb/g) (P = 0.06). The relationship between f‐Hb and Hb, MCV and ferritin was not significant. Poorly differentiated (P = 0.04) and later stage (P = 0.02) R‐CRC had significantly lower f‐Hb compared to L‐CRC.Right‐sided CRC is associated with lower f‐Hb than left. Poorly differentiated and later staged L‐CRC had higher median f‐Hb. These data add to existing evidence suggesting that FIT may be less sensitive for right‐sided CRC. Strategies to mitigate the potential for missed or FIT‐negative right‐sided CRC are required. [ABSTRACT FROM AUTHOR]

Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin‐manganese interaction by nanoplatinum growth, a novel ferritin‐platinum‐manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree‐dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram‐based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase‐like activity can catalyze the generation of O2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF‐1α, blocking the TGF‐β1/Smad signaling pathway. In addition, metformin shows synergy with HIF‐1α reduction in blocking the TGF‐β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real‐time anti‐fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti‐fibrotic therapy with real‐time monitoring. [ABSTRACT FROM AUTHOR]

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case–control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756–9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628–8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1–specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1–14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice—responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines. [ABSTRACT FROM AUTHOR]

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies. [ABSTRACT FROM AUTHOR]

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe2+ to Fe3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products. [ABSTRACT FROM AUTHOR]

Background: Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle. Results: Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. The genetically engineered self-assembled particles neoantigen-FNs with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly drainage to and continuously accumulate in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8+ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier. Conclusions: Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently drainage to lymph nodes and induce efficient antitumor immune responses. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the relationship between hemoglobin levels, anemia and diabetic lower extremity ulcers in adult outpatient clinics in the United States. Methods: A retrospective cross-sectional study was conducted on 1673 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Three logistic regression models were developed to evaluate the relationship between anemia and diabetic lower extremity ulcers. Model 1 adjusted for demographic and socioeconomic variables (age, sex, race and ethnicity, educational level, family income, and marital status). Model 2 included additional health-related factors (BMI, cardiovascular disease, stroke, family history of diabetes, hyperlipidemia, alcohol and smoking status). Model 3 further included clinical and laboratory variables (HbA1c, CRP, total cholesterol, and serum ferritin levels). Stratified analyses were also conducted based on age, sex, HbA1c level, body mass index (BMI), and serum ferritin level. Results: The study included 1673 adults aged 40 years and older, with a mean age of 64.7 ± 11.8 years, of whom 52.6% were male. The prevalence of diabetic lower extremity ulcers (DLEU) was 8.0% (136 participants). Anemia was found in 239 participants, accounting for 14% of the study group. Model 1 showed an OR of 2.02 (95% CI=1.28~3.19) for anemia, while Model 2 showed an OR of 1.8 (95% CI=1.13~2.87). In Model 3, the OR for DFU in patients with anemia was 1.79 (95% CI=1.11~2.87). Furthermore, when serum ferritin was converted to a categorical variable, there was evidence of an interaction between DLEU status and serum ferritin in increasing the prevalence of DLEU. Conclusion: After adjusting for confounding variables, higher levels of anemia were proportionally associated with an increased risk of incident DLEU. These results suggest that monitoring T2DM patients during follow-up to prevent the development of DLEU may be important. However, further prospective studies are needed to provide additional evidence. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder characterized by synovial inflammation that leads to joint damage, bony erosions, and related deformities. Between 30 and 70% of RA patients will experience anemia. Early detection of anemia is of great importance. This study aimed to evaluate the serum level of hepcidin (HEP) in RA patients and to assess its relation to disease activity and anemia. The current cross-sectional study included 44 cases with RA in addition to 44 healthy controls. The disease activity in the RA patient was assessed by using the disease activity score (DAS) 28 score-CRP. The serum levels of HEP and ferritin were assessed in both groups using enzyme-linked immunosorbent assay (ELISA) technique. Results: Hepcidin level in the RA group was statistically significantly higher as compared to the control group (p = 0.001). The prevalence of Anemia of chronic disease (ACD) was 40.9%, and iron deficiency anemia (IDA) was 27.3% which accounted for 68.2% of the total anemia cases. The HEP level was statistically significantly higher in the RA patients with ACD than those without anemia (P = 0.028), RA patients with IDA (P < 0.001), and control group (P < 0.001). There was a statistically significant positive correlation between HEP level and serum ferritin level (p = 0.005). HEP level was significantly and inversely correlated with hemoglobin (Hb) in patients with ACD. Serum HEP level is higher in RA patients with high disease activity than those with moderate activity, low activity, and patients in remission (p = 0.380). However, the difference was not statistically significant. The best cutoff point of HEP level to identify RA patients from healthy controls was > 355.5 Pg/ml. This point showed moderate sensitivity (70.5%) with moderate specificity (63.6%) with a statistically significant value. Conclusions: We found the anemia, and particularly ACD, is more common in RA patients. In RA patients with ACD, serum HEP levels were considerably higher. Although serum HEP showed no diagnostic significance when it came to evaluating disease activity, it could be a dependable non-invasive biomarker for the diagnosis of various forms of anemia in RA patients. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients. Methods: A cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson's correlation coefficient, considering a significance level of p < 0.05. Results: Significant correlations were found between serum biomarkers and periodontal clinical parameters. Phosphorus, creatinine, albumin, ferritin, and creatinine levels correlated significantly with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, p = 0.018, and p = 0.03). While the Ferritin level showed significant correlations with both the Plaque Index and Miller Classes (r = 0.281, p = 0.018 and r = 0.258, p = 0.031), respectively. The Calcium level showed a significant correlation with the Gingival Index (r = 0.266, p = 0.027). Cystatin C level was statistically correlated with mobility (r = 0.258, p = 0.031). Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03). Conclusion: This study provides evidence of a strong association between periodontal disease and chronic kidney disease in Yemeni haemodialysis patients. The findings emphasize the significance of maintaining good oral health in the care of haemodialysis patients. [ABSTRACT FROM AUTHOR]

Introduction: Females with transfusion-dependent β-thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well-chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin. Methods: Fifty adolescent females with TDT were compared to 50 age-matched healthy females. Age of diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin were measured. Magnetic resonance imaging (MRI) pituitary iron content R2* and T2* were measured, and 3-D transabdominal ovarian ultrasound performed. Results: The mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 of them (40%). Compared to controls, adolescent females with TDT had significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. Upon comparing those with ovarian insufficiency and those without, adolescents with TDT having ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* than those without insufficiency. Multivariate-logistic regression showed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT. Conclusion: Adolescent females with TDT have decreased ovarian reserve, AFC, and gonadotropins that are correlated with serum ferritin, pituitary iron load, and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of endocrinological follow-up of females with TDT advising procedures to preserve fertility to those who are likely to have ovarian insufficiency. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia (IDA), the most widespread nutritional disorder, is a persistent global health issue affecting millions, especially in resource-limited geographies. Oral iron supplementation is usually the first choice for exogenous iron administration owing to its convenience, effectiveness and low cost. However, commercially available iron supplementations are often associated with oxidative stress, gastrointestinal side effects, infections and solubility issues. Herein, we aim to address these limitations by employing ferritin proteins—self-assembled nanocaged architectures functioning as a soluble cellular iron repository—as a non-toxic and biocompatible alternative. Our in vitro studies based on PAGE and TEM indicate that bare ferritin proteins are resistant to gastric conditions but their cage integrity is compromised under longer incubation periods and at higher concentrations of pepsin, which is a critical component of gastric juice. To ensure the safe delivery of encapsulated iron cargo, with minimal cage disintegration/degradation and iron leakage along the gastrointestinal tract, we fabricated the surface of ferritin with chitosan. Further, the stoichiometry and absorptivity of iron-chelator complexes at both gastric and circumneutral pH were estimated using Job's plot. Unlike bipyridyl, deferiprone exhibited pH dependency. In vitro kinetics was studied to evaluate iron release from bare and chitosan-fabricated ferritins employing both reductive (in the presence of ascorbate and bipyridyl) and non-reductive (direct chelation by deferiprone) pathways to determine their bio-mineral stabilities. Chitosan-decorated ferritin displayed superior cage integrity and iron retention capability over bare ferritin in simulated gastric fluid. The ability of ferritins to naturally facilitate controlled iron release in conjugation with enteric coating provided by chitosan may mitigate the aforementioned side effects and enhance iron absorption in the intestine. The results of the current study could pave the way for the development of an oral formulation based on ferritin-caged iron bio-mineral that can be a promising alternative for the treatment of IDA, offering better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. Prior studies including ours have shown the abnormal changes in hematopoietic cells in COVID-19 patients. In this article, we are presenting 2 cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. The first case describes a 22-month-old boy presenting with lymphadenopathy, neutropenia, and anemia with concurrent COVID-19 infection without any evidence of a hematolymphoid neoplasm as per bone marrow and lymph node biopsy. However, he presented after 2 months with bone marrow biopsy confirming B-ALL. The second case is that of a 4-year-old girl presenting with B-ALL who has had asymptomatic COVID-19 infection 5 months before this current presentation. Both the cases had complete resolution of COVID-19 infection during the time of presentation with acute leukemia. There were notably 2 rare findings along the course of the patients' illnesses. First, the unusual plasmacytosis in the marrow during active COVID-19 infection in the first patient and the second, is predilection of development of B-ALL following COVID-19. In both the cases the fluorescence in situ hybridization (FISH) studies showed pathologic alteration of the RUNX1 gene. Overall, there are no literature to support a causal association between acute B-ALL and COVID-19. The diagnosis of B-ALL in these patients after COVID-19 infection may be totally unrelated. However, if we consider Greaves proposed 2-hit model for childhood acute leukemia, that an infectious agent can precipitate development of B-ALL in a genetically susceptible individual. Alteration of the RUNX1 gene in both the patients, opens a door for further exploration of the "second-hit" hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF‐MetS association might be U/J‐shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland.We analysed cross‐sectional data from the Viking Health Study‐Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status‐specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2–3) as the reference, were conducted to estimate the SF‐MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI.Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17–3.38] p =.011 for Q1 and 2.10 [1.27–3.49] p =.004 for Q4) This U‐shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15–200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI.Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF‐MetS associations were found in men or PreMW. The ferritin‐MetS association pattern differs between populations and U/J‐shaped associations may exist. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Methods Demographic, clinical and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen paediatric rheumatology centres across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. Results One hundred and sixty-two patients were included in the study. Forty-five of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72–232) vs 199 (130–371) 109/l], ferritin level on admission [1107 (676–2050) vs 2863 (1193–9562) ng/ml], C-reactive protein level [15.4 (2.9–56) vs 90 (32–160) mg/l], erythrocyte sedimentation rate [13 (3–36) vs 43.5 (13–77) mm/h] and fever duration [5 (4–7.5) vs 10 (7–14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. Conclusion Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met. [ABSTRACT FROM AUTHOR]