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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]

AbstractPostnatal iron deficiency, especially from ages 6 to 24 months, has long-term consequences lasting into adolescence and adulthood. We aimed to characterize iron deficiency anemia among infants from one central Israeli district by demographic and laboratory parameters. A retrospective chart review was performed on all infants from a single district who had undergone a complete blood count as part of a routine survey for iron deficiency anemia during 2010–2021. Data retrieved included hemoglobin levels, mean corpuscular volume, and demographic features: sex, sector (non-ultraorthodox Jew, ultraorthodox Jew, and Arab), socioeconomic status, and type of residence. The study group comprised 101,650 infants, aged 9 to 18 months. Iron deficiency anemia, defined as a hemoglobin level <11 g/dL and mean corpuscular volume <70 fl was observed in 4296 (4.2%) of the study infants. Iron deficiency anemia was more prevalent among Arab and ultraorthodox Jewish infants, than non-ultraorthodox Jewish infants (6.6% vs. 6% vs. 3%, respectively). It was also more prevalent among infants of low socioeconomic status, and relatively common among infants of rural residence. We identified two specific sub-populations at risk of developing iron deficiency anemia: Arab and ultraorthodox Jewish infants. We recommend enhancing the nationwide intervention program for both clinicians and parents, thereby treating iron deficiency anemia promptly to avoid short- and long-term deleterious health consequences. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours. In an effort to explore the potential of magnetosomes for cancer treatment, we have explored their degradation process in a 3D human lung carcinoma model at the subcellular level and with nanometre scale resolution. We have used state of the art hard X-ray probes (nano-XANES and nano-XRF), which allow for identification of distinct iron phases in each region of the cell. Our results reveal the progression of magnetite oxidation to maghemite within magnetosomes, and the biosynthesis of magnetite and ferrihydrite by ferritin. [ABSTRACT FROM AUTHOR]

Background: Pediatric palliative care (PPC) patients are at an elevated risk of malnutrition. Nutritional inadequacy can also cause micronutrient deficiencies. These factors can lead to weight loss, stunted growth, and poor quality of life. Despite the prevalence of these issues, limited research exists in the micronutrient status of PPC patients. The purpose of this study was to determine the vitamin B12 and D, iron, ferritin, folate, calcium, phosphorus, and magnesium levels of PPC patients to contribute to a better understanding of their micronutrient needs as well as the appropriate management of diet and treatment approaches. Methods: This was a single-center observational cross-sectional retrospective study. This study evaluated the levels of vitamin B12, 25-hydroxyvitamin D, iron, ferritin, folate, calcium, phosphorus, and magnesium in PPC patients. The patients were classified according to the Chronic Complex Conditions (CCC) v2 and then compared. Results: A total of 3,144 micronutrient data points were collected from 822 hospitalizations of 364 patients. At least one micronutrient deficiency was identified in 96.9% of the patients. The most prevalent deficiencies were observed for iron, calcium, and phosphate. In addition, 25-hydroxyvitamin D deficiency was observed in one-third of patients. Calcium, magnesium, phosphorus, folate, and 25-hydroxyvitamin D were negatively correlated with age. Conclusion: The results of this study indicate that micronutrient deficiencies are highly prevalent in PPC patients. These findings have the potential to contribute to improvements in the nutritional and therapeutic management of patients. [ABSTRACT FROM AUTHOR]

Introduction The COVID-19 pandemic has promoted an intensive investigation into the pathophysiological mechanisms of SARS-CoV-2 infection, risk factors, and its impact on disease severity. Vitamin D has generated significant attention for its potential role in viral prevention and immune defense due to its pleiotropic functions, including immunomodulation and antimicrobial effects. This study aimed to assess serum 25(OH)D3 levels in patients with COVID-19 compared to those with other viral respiratory infections and to evaluate associations of vitamin D levels with symptomatology, clinical characteristics, presence of comorbidities and laboratory investigation. Methods The study included 78 patients admitted to a hospital with COVID-19 (52 patients) or other viral respiratory infections (26 patients). Routine blood biomarkers, markers of inflammation, markers of endothelial dysfunction, serum 25(OH)D3 were analyzed, and patients were classified according to vitamin D levels and presence of comorbidities. Results Most patients had vitamin D levels <30 ng/mL and there was no significant difference in 25(OH)D3 levels between patients with and without COVID-19 (p=0.768). Aging and comorbidity prevalence were significantly increased in the COVID-19 than in the non-COVID-19 group (p<0.001; p=0.049). A significant positive correlation was determined between endocan level and serum ferritin concentration in patients with COVID-19 and vitamin D deficiency. A borderline significantly elevated NLR was observed in patients with COVID-19 who were also vitamin D deficient, compared with the similar non-COVID-19 subgroup (p=0.05). In patients with COVID-19 and insufficient vitamin D, levels of 25(OH)D negatively correlated with endocan. Interestingly, COVID-19 patients with diabetes exhibited significantly lower 25(OH)D3 levels compared to non-diabetic patients (p=0.003), along with higher ferritin levels, suggesting a potential association between vitamin D deficiency and diabetes in COVID-19. Conclusions These findings contribute to the understanding of the complex interplay between vitamin D status, comorbidities, and COVID-19 outcomes, emphasizing the need for further research to elucidate their underlying mechanisms and clinical implications. [ABSTRACT FROM AUTHOR]

Introduction: Ferroportin (Fpn) is the only known iron exporter and plays an essential role in iron homeostasis. Serum concentrations of Fpn in health and/or diseased states are still mostly unknown. Therefore, the aim of this study was to determine the concentration of Fpn in the serum of women of reproductive age (WRA) for the first time, and to establish whether there is a difference in the concentration of Fpn according to ferritin status. Materials and methods: This research included 100 WRA (18-45 years, C-reactive protein (CRP) < 5 mg/L, hemoglobin > 120 g/L). Serum Fpn was measured using Enzyme Linked Immunosorbent Assay (ELISA) method on the analyzer EZ Read 800 Plus (Biochrom, Cambridge, UK). Reference interval was calculated using the robust method. Results: The median concentration of Fpn in the whole study group was 9.74 (5.84-15.69) μg/L. The subgroup with ferritin concentration > 15 μg/L had a median Fpn concentration 15.21 (10.34-21.93) μg/L, which significantly differed from Fpn concentration in the subgroup with ferritin concentration ≤ 15 μg/L (5.93 (4.84-8.36) μg/L, P < 0.001). The reference limits for the Fpn were 2.26-29.81 μg/L with 90% confidence intervals (CI) of 1.78 to 2.83 and 25.37 to 34.33, respectively. Conclusions: The proposed reference interval could help in the future research on iron homeostasis both in physiological conditions and in various disorders, because this is the first study that measured Fpn concentration in a certain gender and age group of a healthy population. [ABSTRACT FROM AUTHOR]

Beta-thalassemia major is a severe hereditary anemia that necessitates regular blood transfusions, leading to iron overload. This condition also affects various biological markers, including ferritin and vitamin D levels, and can influence immune responses and oral health. The Aim of Study To examine the relationship between salivary Porphyromonas gingivalis IgA and IgG levels with the concentrations of ferritin and vitamin D in adolescent affected by Beta-Thalassemia Major. A case-control study was conducted from November 2023 to June 2024, involving 45 beta-thalassemia major adolescents and 45 healthy controls. All subjects were within ages ranged between 12-17 years. Saliva sample was collected and analyzed for estimation of salivary anti-Porphyromonas gingivalis IgA and IgG by using ELISA and blood collected and analyzed to measures s.ferritin and s.vitamin D by Cobas E411 system. The study group exhibited significantly lower mean salivary anti-Porphyromonas gingivalis IgA and IgG levels (40.59± 16.71 pg/ml), (15.23±3.21 pg/ml) compared to the control group (93.06± 55.25pg/ml), (18.92±3.32 pg/ml) (p=0.000) respectively. Serum ferritin (4158.37±542.64 ng/ml vs. 25.11±10.93 ng/ml), and vitamin D levels (9.83±4.69 ng/ml vs. 16.40±12.93 ng/ml) showed significant differences (p<0.05) between study and control groups. Beta-thalassemia major significantly impacts salivary and serum biochemical markers, highlighting the importance of regular monitoring and potential targeted therapies to manage iron overload and associated complications. The reduced immune response against Porphyromonas gingivalis in these patients suggests a need for enhanced oral health care and possibly prophylactic measures. [ABSTRACT FROM AUTHOR]

Malabsorption of iron and/or vitamin B12 and low thyroid hormone levels may cause anemia in patients with hypothyroidism. This cross-sectional study investigates anemia prevalence, types, and potential causes in 69 patients with hypothyroidism. The control group consisted of 31 healthy volunteers. Diagnostic assessments for hypothyroidism and anemia, in addition to participant-completed questionnaires, were conducted. Females with hypothyroidism exhibited a higher anemia prevalence (12:1 ratio) than males. Among L-thyroxine-treated patients, 22.8% had anemia compared to 11.5% in the untreated subclinical group with hypothyroidism (p>0.05). Females under L-thyroxine therapy had significantly lower hemoglobin level than females in the control group (p=0.0001). Also, L-thyroxine-treated females had lower ferritin level compared to the untreated females with hypothyroidism (p=0.026) and females in the control group (p=0.007) while having higher red blood cell distribution width (RDW) compared to the untreated females (p=0.012) and the control group females (p=0.0001). No significant differences in hemoglobin, ferritin, or RDW were found between males with hypothyroidism and the control group. Also, no significant differences were found among patients with hypothyroidism and the control group in Vitamin B12 level. Blood film examination revealed that normochromic normocytic anemia was present in 53.8% of anemic cases with hypothyroidism while hypochromic microcytic anemia was evident in 46.2% of cases. None of the anemic patients had macrocytic anemia. Ferritin level correlated negatively with RDW in patients with hypothyroidism treated with L-thyroxine (r =-0.517, p <0.01). In conclusion, screening and treating anemia in patients with hypothyroidism is recommended. Treatment with L-thyroxine alone may not be sufficient to prevent anemia in hypothyroidism. [ABSTRACT FROM AUTHOR]

Background and Objectives: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation. Materials and Methods: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first‐time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up. Results: About one‐third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre‐menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post‐menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer. Conclusion: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan. [ABSTRACT FROM AUTHOR]

This study provides a preliminary background for the development of a viral vector vaccine for the dengue virus using genetic material encoded by dengue envelope ferritin nanoparticles. Adenoviruses were generated for the recombinant envelope of dengue virus 2 (DENV2) and the envelope human ferritin heavy chain using a two-vector adenovirus system. The primary immunostimulatory activity of the two viruses was analyzed in mice to determine the effect of envelope ferritin nanoparticles. Transfection of a shuttle vector delivered the target gene and packaging vector carrying the packaging signal, and recombinant adenoviruses (rAds) were generated and purified using an ultracentrifugation method. Transduction efficiencies of the generated adenoviruses were confirmed in A549 cells. Purified adenoviruses (8 × 106 PFU/mL) were immunized intramuscularly into 6 weeks old BALB/c mice. Subsequently, the DENV2-specific IgG titer was evaluated 1 and 4 weeks after immunization. Envelope ferritin-immunized mice showed a significant IgG response compared to envelope-only immunized mice at 1 and 4 weeks after immunization, revealing the persistence of the dengue virus-specific IgG response. This method demonstrated the capability of the viral vector vaccine to be used as a carrier for ferritin nanoparticles, instead of direct immunization with ferritin nanoparticles. [ABSTRACT FROM AUTHOR]

Background: There is a lack of standardization of reference intervals (RIs) for ferritin across laboratories, particularly for postmenopausal women. Depending on the RI used, there can be more than a 4-fold difference in the upper limit of normal between laboratories, resulting in potential misinterpretation. Methods: This retrospective study used a large dataset of blood test results from 25,425 healthy participants aged 18 to 97 over a 7-year period. Exclusion criteria were used to screen out individuals with conditions known to affect iron metabolism or raise ferritin as part of the acute phase response. Distributions were assessed using density and Q-Q plots, and age-banded cut-offs were determined. The non-parametric method was used to establish RIs for sex and age bands. Results: For females, 4 age bands were established (18–39, 40–49, 50–59 and 60+). For males, 2 bands were identified (18–39 and 40+). Performance against a validation dataset, followed by an expansive validation against an inclusive dataset, demonstrated the robustness of the derived RIs. Conclusion: This study addresses the inconsistency in serum ferritin RIs by presenting intervals based on demographic parameters. This approach can potentially enhance the accuracy of interpreting serum ferritin levels, assisting clinicians in identifying patients requiring further evaluation. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion: Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement). [ABSTRACT FROM AUTHOR]

Still's disease (SD) is a rare systemic inflammatory disease that is characterized by high fever, polyarthritis, and an evanescent rash as its main symptoms but that may also be complicated by pleuritis and macrophage activation syndrome (MAS). There has been a recent increase in studies on older-onset SD, which presents with less-typical clinical features, such as sore throat, skin lesions, and splenomegaly, but more complications including pleuritis and disseminated intravascular coagulation. Several reports have shown higher levels of inflammatory markers, including serum ferritin, and poorer outcomes in terms of survival and drug-free remission in older patients. In addition, caution is needed when diagnosing SD in older patients because of the increased incidence of differential diagnoses such as infectious diseases, malignancies, and inflammatory diseases. Prognosis is poor in older patients, and treatment-associated infections and severe complications such as MAS are the main cause of mortality. The use of biologics and treatment response may not differ greatly between older and younger patients. Although the data are limited, anti-IL-1 and anti-IL-6 agents may control SD in these patients with careful use and adequate infection prevention. Recent studies that classified adult-onset SD by cluster analysis or latent class analysis showed that older patients form a unique cluster of SD, indicating the need for clinicians to pay more attention to the diagnosis and management of SD in older patients. [ABSTRACT FROM AUTHOR]

Ferritin, an iron storage protein, is ubiquitously distributed across diverse life forms, fulfilling crucial roles encompassing iron retention, conversion, orchestration of cellular iron metabolism, and safeguarding cells against oxidative harm. Noteworthy attributes of ferritin include its innate amenability to facile modification, scalable mass production, as well as exceptional stability and safety. In addition, ferritin boasts unique physicochemical properties, including pH responsiveness, resilience to elevated temperatures, and resistance to a myriad of denaturing agents. Therefore, ferritin serves as the substrate for creating nanomaterials typified by uniform particle dimensions and exceptional biocompatibility. Comprising 24 subunits, each ferritin nanocage demonstrates self-assembly capabilities, culminating in the formation of nanostructures akin to intricate cages. Recent years have witnessed the ascendance of ferritin-based self-assembled nanoparticles, owing to their distinctive physicochemical traits, which confer substantial advantages and wide-ranging applications within the biomedical domain. Ferritin is highly appealing as a carrier for delivering drug molecules and antigen proteins due to its distinctive structural and biochemical properties. This review aims to highlight recent advances in the use of self-assembled ferritin as a novel carrier for antigen delivery and vaccine development, discussing the molecular mechanisms underlying its action, and presenting it as a promising and effective strategy for the future of vaccine development. [ABSTRACT FROM AUTHOR]

Ferritin (Ft) is a protein with a peculiar three-dimensional architecture. It is characterized by a hollow cage structure and is responsible for iron storage and detoxification in almost all living organisms. It has attracted the interest of the scientific community thanks to its appealing features, such as its nano size, thermal and pH stability, ease of functionalization, and low cost for large-scale production. Together with high storage capacity, these properties qualify Ft as a promising nanocarrier for the development of delivery systems for numerous types of biologically active molecules. In this paper, we introduce the basic structural and functional aspects of the protein, and summarize the methods employed to load bioactive molecules within the ferritin nanocage. [ABSTRACT FROM AUTHOR]

Objective: To update the prevalence of male and female athlete Triad risk factors in ultramarathon runners and present exploratory analyses examining correlations between bone mineral density (BMD) and hormones. Design: Multiyear cross-sectional study. Setting: Western States Endurance Run 100-mile race. Participants: Participants were recruited in 2018 and 2019 for our prior cohort. We added an additional cohort in 2021. Assessment of Risk Factors: Participants completed laboratory evaluations of sex hormones, vitamin D, and ferritin (2019 and 2021 cohorts only); dual energy x-ray absorptiometry; and surveys evaluating nutritional habits, menstrual history, and injury history. Main Outcome Measures: The Triad cumulative risk assessment was assessed for each participant. Results: One hundred seventy-nine runners participated (123 men and 56 women). 61.1% of women and 28.1% of men were at moderate or high cumulative risk for the Triad. In women, there were significant correlations between hip and femoral neck BMD and total testosterone (Spearman correlation coefficient r 5 0.58, P 5 0.001; r 5 0.45, P50.01). In men, there were weak, significant correlations (r50.24-0.30, P50.01-0.04) between estradiol and vitamin D at most anatomic sites. Conclusions: Our results build on our prior CJSM publication. With the addition of about 50% more study participants in 2021, we observed a stable, high prevalence of Triad risk factors, which represents a more precise measurement and highlights the need for future Triad research in the ultramarathon population. We found significant exploratory associations between hormones and BMD, which varied considerably from our prior publication and should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis is one of the most significant indicators of a bad prognosis in COVID-19 patients. A novel antifibrotic medication called Nintedanib inhibits several growth factors to prevent neo-angiogenesis while interfering with pulmonary fibrosis processes. The purpose of this research was to look at Nintedanib's efficacy and safety in treating young to middle-aged COVID-19 when Nintedanib is administered as a prophylactic measure. Methodology: This case-control study included 50 COVID-19 confirmed cases, and 50 matched controls admitted at ICU and HDU. The primary endpoint was to assess the oxygen requirement and PaO2/FiO2 ratio among the two groups. Additionally, prognostic laboratory markers including Ferritin, CRP, D-dimer was assessed on days 0, 4, 11 and 15 days. 15-day mortality was determined. Appropriate statistical tests were used for comparison. Results: During the baseline visit, PaO2/FiO2 ratio in case (56.6 ± 34.1) and control (71.16 ± 37.7) with a statistical increase in control group (p=0.04). However, on day 11 and day 15, the PaO2/FiO2 ratio was statistically higher in case group (P<0.05). The oxygen requirement over the follow-up visits in case-group statistically decreased. Except for the baseline, at all follow-up visits, the levels of ferritin, CRP, D-dimer were statistically lower in the case group compared to control group (p<0.05). Additionally, a statistical increase in the mortality in control group was noted at 15th day of the study. Conclusion: Nintedanib treatment has the potential to reduce lung damage in COVID-19 patients and to assist COVID-19 patients prophylactically while disease is active. [ABSTRACT FROM AUTHOR]

Background Cardiac injury caused by iron overload is the leading cause of mortality and morbidity in patients with beta-thalassemia, owing to frequent blood transfusion, increased iron overload, and blood hemolysis. Objective This research aimed to assess several novel cardiac biomarkers in the blood samples of children and adult patients with beta-thalassemia major (βTM), along with their respective control groups. These biomarkers included endothelin 1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), growth differentiation factor-15 (GDF-15), and renalase (RNLS). Methods This case-control study was done on 46 patients with βTM (23 children <18 years, and 23 adults ≥18 years) from the Genetic Hematology Center in Thi-Qar province, Iraq, and 42 comparable controls in 2 groups (21 for each group) in the period from February to April 2023. Results Levels of ET-1, NT-proBNP, ANP, GDF-15, RNLS, and ferritin were higher in the children and adults with βTM than in the control subjects. Conclusion Elevations of the novel cardiac biomarkers ET-1, NT-proBNP, ANP, GDF-15, and RNLS in the sera of children and adult patients with βTM when compared with comparable control subjects confirm that the majority of patients with βTM are at risk of cardiac and cardiovascular complications even when there are no obvious symptoms, especially in children, which gives suitable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: Iron absorption in sickle cell anemia (SCA) remains unclear and studies in adults with SCA are scarce. The aim of this study was to evaluate the iron absorption SCA adults and its association with iron status and hepcidin concentration. Methods: SCA patients (n = 13; SCAtotal) and control participants (n = 10) ingested an oral stable iron isotope (57Fe). Iron absorption was measured by inductively coupled plasma mass spectrometry (ICP-MS) 14 days after isotope administration. Patients with ≥ 1000 ng/mL serum ferritin were considered to present iron overload (IO) (SCAio+; n = 3) and others classified without IO (SCAio-; n = 10). Results: Iron absorption in the control group ranged from 0.3 to 26.5% (median = 0.9%), while it varied from 0.3 to 5.4% in SCAio+ (median = 0.5%) and from 0.3 to 64.2% in the SCAio- (median = 6.9%). Hepcidin median values were 14.1 ng/mL (3.0–31.9 ng/mL) in SCAio-, 6.2 ng/mL (3.3–7.8 ng/mL) in SCAio + and 6.2 ng/mL (0.6–9.3 ng/mL) in control. Iron absorption was associated with ferritin level (r = − 0.641; p = 0.018) and liver iron concentration (LIC; r = − 0.786; p = 0.036) in the SCAtotal group. Conclusion: Our data suggest that SCAio- individuals may be at risk of developing primary IO. Simultaneously, secondary IO may induce physiological adaptation, resulting in reduced iron absorption. Further studies evaluating intestinal iron absorption using larger sample sizes should be conducted to help establish a safe nutrition approach to be adopted and to ensure the security of food-fortifying public policies for these patients. Trial registration: This trial was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt). [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of the simultaneous consumption of sumac powder (RhusCoriaria L.) and ferrous sulfate for six weeks on hematologic indices such as ferritin, hemoglobin (Hb), hematocrit (HCT), and mean corpuscular volume (MCV), inflammation (high sensitivity C-reactive protein), oxidative stress (TAC and MDA) and some physical fitness factors in teenage volleyball players with depleted iron stores (serum ferritin less than 40 ng/ml). In a semi-experimental study, 30 girls aged 15–18 years with three to five years of background in volleyball who were at the special level of preparation with low iron stores were screened and randomly divided into three homogeneous groups (iron supplementation, iron supplementation + sumac powder, and placebo). Capsules containing ferrous sulfate with 50 mg of elemental iron, one gram of sumac powder, and one gram of rice flour (placebo) were consumed daily by the subjects until the end of the study. Compared to the other two groups, only the iron group showed a significant increase in ferritin concentration (P = 0.000), anaerobic power of the upper limb (P = 0.04), anaerobic power of the lower limb (P = 0.01), and agility (P = 0.00). None of the three groups showed any significant changes in Hb, Hct and Mcv (P = 0.57, P = 0.36, P = 0.33), hs-C reactive protein (P = 0.06), lactate (P = 0.89), VO2max (P = 0.75) and activity heart rate (P = 0.26). The results showed that sumac powder not only did not improve the effect of iron supplementation, but also had a negative effect on it. [ABSTRACT FROM AUTHOR]

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+, and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells. [ABSTRACT FROM AUTHOR]

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Background/Objectives: Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. Subjects/Methods: SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio−; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. Results: The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio− patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = −0.775, p = 0.041; SCAio− group: r = −0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio− group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). Conclusion: SCAio+ group had lower iron incorporation in RBC than SCAio− group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. Trial Registration: This trial was registered at www.ensaiosclinicos.gov.br. Identifier RBR-4b7v8pt. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to assess the nutritional status of children and adolescents with celiac disease (CD) in Kuwait and investigate the nutritional deficiencies and sociodemographic factors associated with growth stunting in this population. Methods: This case–control study included 77 CD patients aged 3–18 years diagnosed with CD using IgA anti-tissue transglutaminase and duodenal biopsy and 33 healthy controls. Nutritional status was evaluated based on demographic and clinical characteristics, anthropometric measurements, and biochemical parameters. Univariate and multivariate logistic regression models were used to determine the association between CD and growth stunting. Results: Approximately one-third (31%) of children with CD had stunted growth, 20.8% had a low body mass index for their age, and 5.2% had both growth stunting and wasting. Children with CD had higher odds of iron-deficiency anemia, vitamin D deficiency, anemia, and lower socioeconomic status. They were also younger and had decreased serum levels of vitamin D compared to the controls. These factors were all significantly associated with an increased risk of CD, collectively explaining over 50% of the risk. For growth stunting, lower education status among mothers, family income, and serum ferritin were identified as risk factors. Conclusions: A significant proportion of children and adolescents with CD had malnutrition, overt deficiencies, and impaired growth despite coherence with a gluten-free diet. Recommendation: Routine monitoring and targeted nutritional interventions are recommended for children and adolescents with CD to address malnutrition and growth stunting. Addressing socioeconomic disparities and enhancing maternal education may also help mitigate the risk factors. [ABSTRACT FROM AUTHOR]

Bleomycin exhibits effective chemotherapeutic activity against multiple types of tumors, and also induces various side effects, such as pulmonary fibrosis and neuronal defects, which limit the clinical application of this drug. Macroautophagy/autophagy has been recently reported to be involved in the functions of bleomycin, and yet the mechanisms of their crosstalk remain insufficiently understood. Here, we demonstrated that reactive oxygen species (ROS) produced during bleomycin activation hampered autophagy flux by inducing lysosomal membrane permeabilization (LMP) and obstructing lysosomal degradation. Exhaustion of ROS with N-acetylcysteine relieved LMP and autophagy defects. Notably, we observed that LMP and autophagy blockage preceded the emergence of cellular senescence during bleomycin treatment. In addition, promoting or inhibiting autophagy-lysosome degradation alleviated or exacerbated the phenotypes of senescence, respectively. This suggests the alternation of autophagy activity is more a regulatory mechanism than a consequence of bleomycin-induced cellular senescence. Taken together, we reveal a specific role of bleomycin-induced ROS in mediating defects of autophagic degradation and further regulating cellular senescence in vitro and in vivo. Our findings, conversely, indicate the autophagy-lysosome degradation pathway as a target for modulating the functions of bleomycin. These provide a new perspective for optimizing bleomycin as a clinically applicable chemotherapeutics devoid of severe side-effects. Abbreviations: AT2 cells: type II alveolar epithelial cells; ATG7: autophagy related 7; bEnd.3: mouse brain microvascular endothelial cells; BNIP3L: BCL2/adenovirus E1B interacting protein 3-like; CCL2: C-C motif chemokine ligand 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; FTH1: ferritin heavy polypeptide 1; γ-H2AX: phosphorylated H2A.X variant histone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cells; HT22: hippocampal neuronal cell lines; Il: interleukin; LAMP: lysosomal-associated membrane protein; LMP: lysosome membrane permeabilization; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NCOA4: nuclear receptor coactivator 4; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; RPS6KB/S6K: ribosomal protein S6 kinase; SA-GLB1/β-gal: senescence-associated galactosidase, beta 1; SAHF: senescence-associated heterochromatic foci; SASP: senescence-associated secretory phenotype; SEC62: SEC62 homolog, preprotein translocation; SEP: superecliptic pHluorin; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to compare serum ferritin and iron levels and periodontal status in pre‐ and post‐menopausal female patients. Materials and Methods: A total of 108 systemically healthy patients were included in the study, 63 patients in the pre‐menopause group and 45 patients in the post‐menopause group. The periodontal diagnosis was made according to the new periodontal disease classification of the American Academy of Periodontology and the European Federation of Periodontology Serum Iron (μg/dL) and Serum Ferritin (ng/mL) values were analysed in patients divided into groups according to menopausal status and periodontal status. Result: The mean ferritin in pre‐menopausal women (34.96 ± 27.87 ng/mL) was lower than the mean ferritin in post‐menopausal women (64.24 ± 36.05 ng/mL), and this difference was found to be statistically significant (P<0.001). There was no statistically significant difference between the averages of iron and ferritin according to periodontal diagnosis in pre‐menopausal women (P = 0.200 and P = 0.858). A statistically significant difference was found between serum ferritin averages according to periodontal diagnosis in post‐menopausal women (P < 0.001). Serum ferritin at % Interdental bone loss = 0 in Post‐M was 33.93 ± 8.65 ng/mL; 47.51 ± 16.17 ng/mL in Stage 1 periodontitis; 72.66 ± 18.12 ng/mL in Stage 2 periodontitis; It was found to be 87.4 ± 47.1 ng/mL in Stage 3–4 periodontitis. Conclusion: Serum ferritin values might vary depending on the presence or severity of periodontitis in post‐menopausal women. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia, characterized by elevated low‐density lipoprotein (LDL) cholesterol levels, is a significant risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in cholesterol metabolism by regulating LDL receptor degradation, making it a therapeutic target for mitigating hypercholesterolemia‐associated risks. In this context, we aimed to engineer human H ferritin as a scaffold to present 24 copies of a PCSK9‐targeting domain. The rationale behind this protein nanoparticle design was to disrupt the PCSK9–LDL receptor interaction, thereby attenuating the PCSK9‐mediated impairment of LDL cholesterol clearance. The N‐terminal sequence of human H ferritin was engineered to incorporate a 13‐amino acid linear peptide (Pep2‐8), which was previously identified as the smallest PCSK9 inhibitor. Exploiting the quaternary structure of ferritin, engineered nanoparticles were designed to display 24 copies of the targeting peptide on their surface, enabling a multivalent binding effect. Extensive biochemical characterization confirmed precise control over nanoparticle size and morphology, alongside robust PCSK9‐binding affinity (KD in the high picomolar range). Subsequent efficacy assessments employing the HepG2 liver cell line demonstrated the ability of engineered ferritin's ability to disrupt PCSK9–LDL receptor interaction, thereby promoting LDL receptor recycling on cell surfaces and consequently enhancing LDL uptake. Our findings highlight the potential of ferritin‐based platforms as versatile tools for targeting PCSK9 in the management of hypercholesterolemia. This study not only contributes to the advancement of ferritin‐based therapeutics but also offers valuable insights into novel strategies for treating cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD. Methods: A comprehensive search was conducted across five databases, leading to the selection of 18 papers for in‐depth analysis. These studies collectively involved 381 PD patients, 60.3% were males. Results: No consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron‐chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients. Conclusion: While iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis‐stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention. [ABSTRACT FROM AUTHOR]

Ferroptosis is implicated in viral neuropathogenesis and may underlie HIV-associated neurocognitive impairment (NCI). Emerging data also suggest differences in brain iron transport by sex. We hypothesized that circulating ferritins that inhibit ferroptosis associate with neurocognitive function and NCI in people with HIV (PWH) in a sex-biased manner. Serum ferritin heavy-chain-1 (FTH1), ferritin light-chain (FTL), and urinary F2-isoprostanes (uF2-isoPs, specific lipid peroxidation marker) were quantified in 324 PWH (including 61 women) with serial global (NPZ-4) and domain-specific neurocognitive testing. Biomarker associations with neurocognitive test scores and NCIs were evaluated by multivariable regression; correlations with uF2-isoPs were also assessed. Higher FTL and FTH1 levels were associated with less NCI in all PWH (adjusted odds ratios 0.53, 95% confidence interval (95% CI) 0.36–0.79 and 0.66, 95% CI 0.45–0.97, respectively). In women, higher FTL and FTH1 were also associated with better NPZ-4 (FTL adjusted beta (β) = 0.15, 95% CI 0.02–0.29; FTL-by-sex βinteraction = 0.32, p = 0.047) and domain-specific neurocognitive test scores. Effects on neurocognitive performance persisted for up to 5 years. Levels of both ferritins correlated inversely with uF2-isoPs in women (FTL: rho = −0.47, p < 0.001). Circulating FTL and FTH1 exert sustained, sex-biased neuroprotective effects in PWH, possibly by protecting against iron-mediated lipid peroxidation (ferroptosis). Larger studies are needed to confirm the observed sex differences and further delineate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Beta-thalassemia major is an inherited hematologic disorder that is characterized by decreased or lack in the synthesis of beta-hemoglobin sequence. An increase in ferritin leads to a decrease in leptin in healthy individuals. This study aimed to compare leptin and ferritin levels in the patients with beta-thalassemia major and healthy individuals. Material and Methods: This cross-sectional study was conducted in 2018-2019. The study participants were divided into two groups including 57 patients with beta-thalassemia major in the case group and 57 healthy volunteers in the control group. Leptin and ferritin levels were measured using the ELISA kit. The data were entered into SPSS 21 software and were compared and analyzed using the T-test. Results: The mean leptin level in the healthy individuals and patients with beta-thalassemia major was 10.17 ± 8.29 ng/ml and 3.23 ± 3.22 ng/ml, respectively. The ferritin level in healthy individuals was 99.14 ± 90.5 ng/ml compared to 1233.456 ± 0.701 ng/ml in the patients with beta-thalassemia major. Conclusion: In beta-thalassemia major patients, the leptin level was lower compared to healthy individuals. In addition, an increase in ferritin levels leads to a decrease in leptin levels in healthy individuals. However, this finding was not observed in patients with beta-thalassemia major. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has had a substantial influence on healthcare systems, requiring early prognosis for innovative therapies and optimal results, especially in individuals with comorbidities. AI systems have been used by healthcare practitioners for investigating, anticipating, and predicting diseases, through means including medication development, clinical trial analysis, and pandemic forecasting. This study proposes the use of AI to predict disease severity in terms of hospital mortality among COVID-19 patients. Methods: A cross-sectional study was conducted at King Abdulaziz University, Saudi Arabia. Data were cleaned by encoding categorical variables and replacing missing quantitative values with their mean. The outcome variable, hospital mortality, was labeled as death = 0 or survival = 1, with all baseline investigations, clinical symptoms, and laboratory findings used as predictors. Decision trees, SVM, and random forest algorithms were employed. The training process included splitting the data set into training and testing sets, performing 5-fold cross-validation to tune hyperparameters, and evaluating performance on the test set using accuracy. Results: The study assessed the predictive accuracy of outcomes and mortality for COVID-19 patients based on factors such as CRP, LDH, Ferritin, ALP, Bilirubin, D-Dimers, and hospital stay (p-value ≤ 0.05). The analysis revealed that hospital stay, D-Dimers, ALP, Bilirubin, LDH, CRP, and Ferritin significantly influenced hospital mortality (p ≤ 0.0001). The results demonstrated high predictive accuracy, with decision trees achieving 76%, random forest 80%, and support vector machines (SVMs) 82%. Conclusions: Artificial intelligence is a tool crucial for identifying early coronavirus infections and monitoring patient conditions. It improves treatment consistency and decision-making via the development of algorithms. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis—including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio—and MetS. In this descriptive cross-sectional study, 209 participants aged 24–70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment—Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS. [ABSTRACT FROM AUTHOR]

Background and Aim: In females of various species and experimental animals, iron (Fe) status in follicular fluid (FF) is associated with local physiological reproductive events related to follicle development, steroidogenesis, and oocyte maturation. However, these mechanisms remain unknown. This study aimed to determine and compare the intrafollicular and plasma concentrations of Fe, ferritin (Ferr), and transferrin (TRF) in cycling mares. Materials and Methods: Sixty ovaries were collected during the breeding season from 30 clinically normal mares raised for slaughterhouse meat production. Blood samples were collected before slaughter. Follicles were classified into three categories according to size: Small (20–30 mm; n = 20), medium (≥31–40 mm; n = 20), and large (≥41 mm; n = 20). The FF samples, after collection, were immediately taken to the laboratory for processing and were centrifuged, and the Fe and Ferr concentrations in the supernatant and plasma were determined by spectrophotometry. Results: Although intrafollicular Fe and Ferr were similar to plasma, TRF was significantly higher in FF than in systemic circulation (p < 0.05). Follicular development does not modify the status of Fe in the mare. Conclusion: Based on this evidence, it is possible that the acquisition of this molecule possibly originated from a local de novo source, whereas their diffusion through ultrafiltration does not play a relevant role. These results provide new scientific insights into the status of follicle Fe, suggesting its involvement in normal ovarian functions in mares.

Abstract 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

Abstract 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

Abstract Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of

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.

Ferritin, an iron transport protein, is an acute phase protein of inflammation and oxidative stress (OS), a biomarker of cytolysis and ferroptosis. Inflammation, OS and iron overload are characteristic processes of the pathophysiology of aging. Human placental hydrolysates (HPHs) are promising hepatoprotective agents for anti-aging therapy. The goal of the team of authors was to systematize data on ferritin as a marker of aging and to identify peptides that counteract the aging pathophysiology, including through the regulation of iron and ferritin metabolism, in the HPH Laennec (manufactured by Japan Bioproducts). The results of basic and clinical studies confirm the above relationships and indicate that blood ferritin levels characterize the chronological and biological aging of the human body.

Thalassemia is a severe genetic blood disorder, and several organs, including eyes, can be affected. The mechanism of ocular abnormalities in thalassemia is multifactorial; one of them is regular blood transfusion, which can cause iron overload. Ocular abnormalities can also occur because of the side effects of iron chelators. This study evaluated ocular involvement in children with Beta-thalassemia major and its association with serum ferritin levels.

Anemia is a global health problem, affecting about a quarter of the world's population, especially women of reproductive age and young children. In 50–75% of cases, anemia is secondary to iron deficiency (ID). Despite the high prevalence of heavy menstrual bleeding (HMB), the associated iron deficiency disorders are underestimated, although they sharply reduce the quality of life and carry significant risks for the mother, fetus and newborn in case of pregnancy. For this purpose, routine screening of girls and women of reproductive age for the presence of ID and anemia is recommended. The new FIGO initiative aims to raise awareness among women and clinicians about the relationship between HMB and ID conditions. Of key importance are: early diagnosis of HMB, elimination of the possible cause, identification of associated iron deficiency disorders, especially preclinical forms. The main task of the gynecologist is to prescribe therapy aimed at quickly stopping high monthly iron losses and replenishing the existing ID. According to Russian clinical guidelines, combined oral contraceptives and an intrauterine system with levonorgestrel are considered first-line therapy to reduce the volume of menstrual blood loss in patients with HMB who require contraception. Qlaira® and Mirena® are the only hormonal drugs registered for contraception and the treatment of HMB not associated with structural disorders of the uterus, since their high effectiveness in reducing menstrual blood loss, restoring hemoglobin and ferritin levels has been confirmed in studies with a high level of evidence.

Objective To investigate the feasibility of granzyme B (GB) promoter-controlled ferritin heavy chain (FTH1) reporter gene expression for monitoring the activation status of chimeric antigen receptor T cells (CAR-T) by magnetic resonance imaging (MRI). Methods Cytotoxic T lymphocytes (CTLs) were screened by Ficoll density gradient centrifugation and flow sorting. The GB promoter and FTH1 gene were ligated together with disialoganglioside 2 (GD2) CAR, and lentiviral vectors were transfected into CTLs to construct GD2-CAR-T/pGB-FTH1 cells. GD2-CAR-T/pCMV-FTH1, GD2-CAR-T, and T cells served as control cells. CytoTox96@non-radioactive cytotoxicity was used to detect the killing effect of each group of cells after co-culture with human neuroblastoma cells (SK-N-SH). ELISA was employed to detect the coincubation factor as well as the amount of GB secretion. Western blotting, Prussian blue staining and cellular MRI were applied to detect the expression of the FTH1 gene after co-culture. Results CTLs were successfully obtained, and then GD2-CAR-T/pGB-FTH1, GD2-CAR-T/pCMV-FTH1 and GD2-CAR-T cells were constructed. The killing effect, co-incubation factor and GB secretion of the above 3 groups of cells were significantly higher than those of the T cells, and the level of GB expression was highest at day 1, and then decreased in order at day 3 and day 7 after co-culturing with SK-N-SH cells. The relative expression of FTH1 and iron content of the GD2-CAR-T/pGB-FTH1 cells showed the same trend as GB expression, and the MRI signals were gradually increased. There were no significant differences in the relative expression of FTH1, iron content and MRI signals in the GD2-CAR-T/pCMV-FTH1 cells at all time points. No FTH1 expression or iron aggregation was observed in the GD2-CAR-T and T cells groups. Conclusion MRI based on the FTH1 reporter gene driven by the granzyme B promoter can reflect the GB expression level and tumor killing effect of CAR-T cells, which provides a potential real-time visual means to monitor the cell activation status for CAR-T therapy.

Abstract 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. Graphical Abstract

Abstract Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours. In an effort to explore the potential of magnetosomes for cancer treatment, we have explored their degradation process in a 3D human lung carcinoma model at the subcellular level and with nanometre scale resolution. We have used state of the art hard X-ray probes (nano-XANES and nano-XRF), which allow for identification of distinct iron phases in each region of the cell. Our results reveal the progression of magnetite oxidation to maghemite within magnetosomes, and the biosynthesis of magnetite and ferrihydrite by ferritin. Graphical Abstract

Background Current knowledge on iron's role in rheumatoid arthritis (RA) development is very limited, with studies yielding inconsistent findings. We conducted a two-sample Mendelian randomization study to assess the associations of iron status with the risk of RA.

Background: Mucormycosis is a rare and aggressive opportunistic fungal infection that has grown significantly in recent years. This infection is rarely seen in healthy people. Mucormycosis usually appears as an acute infection with manifestations in the rhino-cerebral, pulmonary and skin areas, and sometimes its manifestations can be seen as a widespread infection. The special importance of mucormycosis is due to its high mortality rate, which leads to death in 75 to 80 percent of cases. The specific susceptibility of some patients to mucormycosis points to the importance of iron absorption in the pathogenesis of mucormycosis, therefore, we decided to investigate the relationship between serum iron and ferritin levels and mucormycosis disease in patients with underlying factors predisposing to COVID-19. Methods: This study is a case-control type, in which patients with mucormycosis after contracting COVID-19 and also with a history of diabetes mellitus as the case group and patients with COVID-19 and a history of diabetes mellitus are considered as the control group and the serum level of iron and ferritin will be measured and compared in both groups and the outcome of the study will be determined based on the obtained results.The study took place in hospitals of the Kermanshah university of medical sciences in the Kermanshah city from March 2021 to March 2022. Results: In this study, 38 patients were examined in two groups of patients with mucormycosis along with COVID-19 and diabetes in the case group and patients with COVID-19 and diabetes in the control group with an average age of 63 years. In this study, there was no significant difference between the average age in the two studied groups. However, a significant difference was observed between serum iron and ferritin levels in two groups. Conclusion: Hyperferritinemia is considered not only as an indicator of the systemic inflammatory process in the infection of COVID-19, but also indicates an increase in free iron level, which, as a result, contributes to the growth and spread of the fungus (mucormycosis).

[Display omitted] Notwithstanding the progress made, cargo molecules encapsulated within ferritin via oral administration in the gastric environment remains a persistent challenge. This study focuses on the strategic enhancement of ferritin stability in harsh gastric environment. By taking advantagie of computational-assisted design, we strategically introduced up to 96 disulfide bonds along three key inter-subunit interfaces to one single ferritin molecule with human H-chain ferritin and shrimp (Marsupenaeus japonicus) ferritin as starting materials, producing two kinds of robust ferritin nanocages with markedly enhanced acid and protease (pepsin and rennin) resistance. The crystal structure of ferritin nanocage confirmed our design at an atomic level. Encapsulation experiments demonstrated successful loading of bioactive cargo molecules (e.g., doxorubicin) into the engineered ferritin nanocages, with pronouncedly improved protection against leakage under acidic condition and the presence of pepsin and rennin as compared to their native counterparts. This study presents a potential approach for the design and engineering of protein nanocages for oral administration. [ABSTRACT FROM AUTHOR]

This study determines the association between adult Saudi Arabian coffee consumption and serum iron levels. The extensive Saudi Arabian population, including both sexes — male and female, participated in this cross-sectional community-based study from 1 October 2020 to 31 June 2022. The participants were selected arbitrarily using the systematic simple random position. The current study enrolled 113 participants with a mean age of 33 years, including 94 (83.2%) females and 19 (16.8%) males. The concentration of iron absorption assessed among 62 individuals who participated in the group of occasional coffee drinkers was higher (54.9%) than the 51 individuals who participated in the group of regular coffee drinkers (45.1%). In daily coffee consumption, paired samples statistics in mean baseline WBC level (103/μl) was 6.396. On day 31 of June 2022, WBC level (103/μl) was 6.114. Paired samples statistics in mean baseline iron level was 44.29. On day 31 of June 2022, iron level was 72.15. The paired samples correlation in baseline and day 31 iron levels was 0.719, with a significant difference of 0.000. It is critical to acquire the most recent information and local statistics on the frequency of low serum iron levels in Saudi Arabia's diverse adult population. The adult population of Saudi Arabia correlates with coffee consumption and changes in serum ferritin or iron levels and WBC counts. Neither the WBC numbers nor the iron levels were significantly altered. Further research is needed to determine the potential mechanisms causing these relationships. [ABSTRACT FROM AUTHOR]

Ergosterol possesses a variety of physiological activities, however, its application is limited due to its poor water solubility and photosensitivity. In this study, by using the ultrasonic-assisted heating method, recombinant human H-ferritin (rHuHF)–ergosterol nanocomposites (FEs) were designed, and after the characterization, the light stability, serum stability, sustained release character, and cholesterol-lowering property in vitro were analyzed. The results showed that FEs maintained a spherical morphology with the same particle size as rHuHF. About 17 ergosterol molecules were successfully encapsulated in one ferritin molecule with an encapsulation rate of (27.28 ± 0.29)% and a drug loading of (1.63 ± 0.02)%. The light stability of FEs was increased compared with free ergosterol molecules. The FEs also exhibited good serum stability. The results of simulated gastrointestinal digestion indicated that the rHuHF cage was able to prolong the release of ergosterols. FEs digesta can reduce the solubility of cholesterol in micelles. Additionally, molecular docking displayed that ergosterol can competitively inhibit cholesterol binding to human Niemann-Pick C1-Like 1 (NPC1L1), which might play an important role in preventing the delivery of cholesterol to the membrane for accumulation. This work offers an approach to encapsulate and deliver ergosterol depending on the advantage of ferritin nanocage, which has the potential to be applied in food industry. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a significant impact globally, and understanding the relationship between inflammatory markers and disease progression is crucial for effective management. This retrospective study aimed to examine the association between various inflammatory markers, such as C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), D-dimer, ferritin, and procalcitonin (PCT), and the characteristics of disease progression and outcomes in individuals affected by COVID-19. Methods: This study collected raw data from 470 patients who tested positive for SARS-CoV-2 using RT-PCR. Results: The logistic regression analysis revealed that elevated LDH levels were associated with male gender, ICU admission, low oxygen saturation (O2 < 93%), the need for mechanical ventilation, death, and the presence of lung infiltrates. Higher D-dimer levels were associated with older age, diabetes mellitus, cardiac disease, and low oxygen saturation. Ferritin levels were significantly associated with older age, ICU admission, low oxygen saturation, mechanical ventilation, and lung infiltrates. In contrast, CRP was only significant regarding lung infiltrates and procalcitonin levels were not significantly associated with any of the examined factors. Conclusion: This study highlights the importance of monitoring key inflammatory markers, such as LDH, D-dimer, and ferritin, as they are significantly associated with the severity of COVID-19 illness. These findings can inform clinical decision-making and guide the development of targeted interventions to improve patient outcomes.