Search

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs), attributed to their poor entry across the blood–brain barrier (BBB), emphasize the need to bring novel approaches to enhance the entry across the BBB. One such approach is conjugating the antibodies that bind brain proteins responsible for NDs with the transferrin molecule. This glycoprotein transports iron into cells, connecting with the transferrin receptors (TfRs), piggybacking an antibody–transferrin complex that can subsequently release the antibody in the brain or stay connected while letting the antibody bind. This process increases the concentration of antibodies in the brain, enhancing therapeutic efficacy with targeted delivery and minimum systemic side effects. Currently, this approach is experimented with using drug-transferring conjugates assembled in vitro. Still, a more efficient and safer alternative is to express the conjugate using mRNA technology, as detailed in this paper. This approach will expedite safer discoveries that can be made available at a much lower cost than the recombinant process with in vitro conjugation. Most importantly, the recommendations made in this paper may save the antibodies against the NDs that seem to be failing despite their regulatory approvals. [ABSTRACT FROM AUTHOR]

Introduction: Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP. Aim: Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain. Methods: Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin. Results: There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p = 0.99), tolerability (28.6% vs 12%, p = 0.17), infectious complications (57.14% vs 36%, p = 0.12), mortality (31.7% vs 20%, p = 0.69), hospital stay (19.5 vs 23.5 days, p = 0.86), CRP (74.4 vs 59 mg/L, p = 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p = 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p = 0.68) in both groups. Conclusion: Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis. Clinical trial registration: Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188). [ABSTRACT FROM AUTHOR]

Abstract Background Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. Methods This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). Results C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P

Wenying Deng,1,* Zeyi Zhao,1,* Tao Zou,2 Tongdong Kuang,3,* Jing Wang1,* 1School of Basic Medical Sciences, University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China; 2Department of Cardiovascular Medicine, First Affiliated Hospital of University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China; 3Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi Province, 541199, People’s Republic of China*These authors contributed equally to this workThese authors contributed equally to this studyCorrespondence: Tongdong Kuang, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, 541199, People’s Republic of China, Email 594536067@qq.com Jing Wang, School of Basic Medical Sciences, University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China, Tel +86 15200735915, Email 738212405@qq.comAbstract: Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels, resulting in multi-organ dysfunction and various complications. Fusion proteins can form multifunctional complexes by combining the target proteins with partner proteins. It has significant advantages in improving the performance of the target proteins, extending their biological half-life, and enhancing patient drug compliance. Fusion protein-based drugs have emerged as promising new drugs in diabetes therapeutics. However, there has not been a systematic review of fusion protein-based drugs for diabetes therapeutics. Hence, we conducted a comprehensive review of published literature on diabetic fusion protein-based drugs for diabetes, with a primary focus on immunoglobulin G (IgG) fragment crystallizable (Fc) region, albumin, and transferrin (TF). This review aims to provide a reference for the subsequent development and clinical application of fusion protein-based drugs in diabetes therapeutics.Keywords: diabetes mellitus, fusion protein, Fc protein, glucagon-like peptide 1 receptor agonists, transferrin, albumin

Homeostasis preservation is essential for animal survival, and any event that causes a disturbance in homeostasis is defined as a stressor. Here, we aimed to evaluate the effect of scratch brushes and stages as an environmental enrichment to alleviate stress in dairy goats. Twenty-four mixed-breed goats were divided into two groups according to common physiological conditions in breeding farms: milking and dry (milk-producing and non-milk-producing, respectively). Ten days after exposure to environmental enrichment treatment or not (control), blood was sampled. Following the enrichment, we observed a reduction in reactive oxidative stress metabolites, advanced glycation end products (AGEs), and their binding protein (transferrin) in the dry goats, as determined by an ELISA. In contrast, no change in AGEs, along with an increase in transferrin levels, was observed in the milking goats. Moreover, oxytocin levels decreased in the dry and increased in the milking goats, while serotonin levels increased in the dry and remained unchanged in the milking goats. Additionally, gene expression of the cytokines, IL-6 and IL-1ß, and anti-oxidative proteins, lysozyme and transferrin (in peripheral blood leukocytes), as determined by qPCR, presented the same pattern: down-regulation in the dry or up-regulation in the milking goats. In conclusion, a reliable methodology was developed for measuring husbandry stress in goats and to improve dairy goats’ husbandry practice. Current environmental enrichment produced different responsiveness in goats correlated to their physiological status: beneficial effect in dry goats, detrimental effect in milking goats.

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The role of Tf in iron metabolism involves both the uptake of iron from Tf by various cells, as well as the endocytosis mediated by the complex of Tf and the transferrin receptor (TfR). The direct conjugation of the therapeutic compound and immunotoxin studies using Tf peptide or anti-Tf receptor antibodies as targeting moieties aims to prolong drug circulation time and augment efficient cellular drug uptake, diminish systemic toxicity, traverse the blood-brain barrier, restrict systemic exposure, overcome multidrug resistance, and enhance therapeutic efficacy with disease specificity. This review primarily discusses the various biological actions of Tf, as well as the development of Tf-targeted nano-based drug delivery systems. The goal is to establish the use of Tf as a disease-targeting component, accentuating the potential therapeutic applications of this protein. [ABSTRACT FROM AUTHOR]

AbstractAs a typical glycoprotein and potential disease biomarker, transferrin (TrF) plays an important role in binding and transporting iron ions and regulating homeostasis in vivo. However, conventional serum TrF detection technologies often need complex sample pretreatments and long analysis times. Hence, fluorescent magnetic molecular imprinted polymers (FMMIPs) were prepared for the determination of TrF in human serum, which combined the high sensitivity of fluorescence and the specificity of molecularly imprinted polymers. This material is a labor-saving, easy-to-use, and noninvasive biomarker, which provides the determination of serum TrF with high selectivity. Moreover, the preparation and fluorescent properties of FMMIPs were systematically investigated. Under the optimized conditions, the prepared FMMIPs had a good adsorption and fast response with a low relative standard deviation (less than 5%) for TrF with an imprinting factor of 3.21 and detection limit of 0.107 μg/mL. This material provides direct, sensitive, and rapid protein determination for TrF in serum. [ABSTRACT FROM AUTHOR]

Iron is essential for all the lives and mitochondria integrate iron into heme and Fe-S clusters for diverse use as cofactors. Here, we screened mitochondrial proteins in KU812 human chronic myelogenous leukemia cells by glutathione S-transferase pulldown assay with PCBP2 to identify mitochondrial receptors for PCBP2, a major cytosolic Fe(II) chaperone. LC–MS analyses identified TOM20, sideroflexin-3 (SFXN3), SFXN1 and TOM70 in the affinity-score sequence. Stimulated emission depletion microscopy and proteinase-K digestion of mitochondria in HeLa cells revealed that TOM20 is located in the outer membrane of mitochondria whereas SFXN3 is located in the inner membrane. Although direct association was not observed between PCBP2 and SFXN3 with co-immunoprecipitation, proximity ligation assay demonstrated proximal localization of PCBP2 with TOM20 and there was a direct binding between TOM20 and SFXN3. Single knockdown either of PCBP2 and SFXN3 in K562 leukemia cells significantly decreased mitochondrial catalytic Fe(II) and mitochondrial maximal respiration. SFXN3 but not MFRN1 knockout (KO) in mouse embryonic fibroblasts decreased FBXL5 and heme oxygenase-1 (HO-1) but increased transferrin uptake and induced ferritin, indicating that mitochondrial iron entry through SFXN3 is distinct. MFRN1 KO revealed more intense mitochondrial Fe(II) deficiency than SFXN3 KO. Insufficient mitochondrial heme synthesis was evident under iron overload both with SFXN3 and MFRN KO, which was partially reversed by HO-1 inhibitor. Conversely, SFXN3 overexpression caused cytosolic iron deficiency with mitochondrial excess Fe(II), which further sensitized HeLa cells to RSL3-induced ferroptosis. In conclusion, we discovered a novel pathway of iron entry into mitochondria from cytosol through PCBP2-TOM20-SFXN3 axis. [ABSTRACT FROM AUTHOR]

Human transferrin (htf) plays a crucial role in regulating the balance of iron within brain cells; any disruption directly contributes to the development of Neurodegenerative Diseases (NDs) and other related pathologies, especially Alzheimer's Disease (AD). In recent times, a transition towards natural compounds is evident to treat diseases and this shift is mainly attributed to their broad therapeutic potential along with minimal side effects. Capsaicin, a natural compound abundantly found in red and chili peppers, possess neuroprotective potential. The current work targets to decipher the interaction mechanism of capsaicin with htf using experimental and computational approaches. Molecular docking analysis revealed that capsaicin occupies the iron binding pocket of htf, with good binding affinity. Further, the binding mechanism was investigated atomistically using Molecular dynamic (MD) simulation approach. The results revealed no significant alterations in the structure of htf implying the stability of the complex. In silico observations were validated by fluorescence binding assay. Capsaicin binds to htf with a binding constant (K) of 3.99 × 106 M-1, implying the stability of the htfcapsaicin complex. This study lays a platform for potential applications of capsaicin in treatment of NDs in terms of iron homeostasis. [ABSTRACT FROM AUTHOR]

Background: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. Methods: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. Results: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. Conclusions: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway. [ABSTRACT FROM AUTHOR]

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron‐dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron‐containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long‐acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome‐targeted magnetic nanotorquer (T7‐MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7‐MNTs target lysosomes via the transferrin receptor‐mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7‐MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto‐mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency‐ and time‐dependent lipid peroxidization. Importantly, in vivo studies show that T7‐MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long‐acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical‐based ferroptosis inducers for cancer treatment. [ABSTRACT FROM AUTHOR]

The prevalence of generalised anxiety disorder (GAD) is high. However, the underlying mechanisms remain elusive. Proteomics techniques can be employed to assess the pathological mechanisms involved in GAD. Twenty-two drug-naive GAD patients were recruited, their serum samples were used for protein quantification and identified using Tandem Mass Tag and Multiple Reaction Monitoring (MRM). Machine learning models were employed to construct predictive models for disease occurrence by using clinical scores and target proteins as input variables. A total of 991 proteins were differentially expressed between GAD and healthy participants. Gene Ontology analysis revealed that these proteins were significantly associated with stress response and biological regulation, suggesting a significant implication in anxiety disorders. MRM validation revealed evident disparities in 12 specific proteins. The machine learning model found a set of five proteins accurately predicting the occurrence of the disease at a rate of 87.5%, such as alpha 1B-glycoprotein, complement component 4 A, transferrin, V3-3, and defensin alpha 1. These proteins had a functional association with immune inflammation. The development of generalised anxiety disorder might be closely linked to the immune inflammatory stress response. [ABSTRACT FROM AUTHOR]

Objective: to explore the influences of a trans-theoretical model-based diet nursing intervention on sarcopenia and quality of life in maintenance hemodialysis patients. Methods: the clinical data of 243 patients with maintenance hemodialysis (MHD) admitted to our hospital from January 2019 to August 2020 were retrospectively analyzed. A 1:1 orientation score matching (PSM) method was adopted, and patients with different intervention methods were matched based on gender, age, education time, dialysis age, body mass index, underlying diseases, annual income, and whether they were malnourished. Finally, 82 cases were included in the control group (routine nursing and dietary guidance) and 80 cases in the intrevention group (dietary nursing intervention based on the trans-theoretical model), respectively. Results: after PSM, 82 cases in the control group and 80 cases in the intrevention group were included in the study. After the intervention, the incidence of sarcopenia, the extracellular water rate (ECF/TBF) value, and the malnutrition rate of the intrevention group were lower than those of the control group (p < 0.05); the scores of self-care, facing difficulties, potassium intake management, salt intake management, fluid restriction management, the levels of serum albumin, prealbumin and transferrin were all higher than those of the control group (p < 0.05); the SF-36 Concise Health Scale score of the intrevention group was higher than that of the control group (p < 0.05). The 1-year survival rate in the intrevention group (95.00 %) was higher than that in the control group (85.37 %) (p < 0.05). Conclusion: a TTM-based diet nursing intervention can help improve the dietary management behavior of MHD patients, prevent malnutrition, reduce the incidence of sarcopenia, and improve their quality of life and survival rate. [ABSTRACT FROM AUTHOR]

Although iron is a bio-essential metal, dysregulated iron acquisition and metabolism result in production of reactive oxygen species (ROS) due to the Fenton catalytic reaction, which activates ferroptotic cell death pathways. The lipophilic Fe(III)-chelator chlorquinaldol (L; i.e., 5,7-dichloro-8-hydroxy-2-methylquinoline) strongly favors the formation of a highly stable binuclear Fe(III) complex [(L2Fe)2(μ-O)] (1) that can mimic the function of the Fe(III)-transferrin complex in terms of the strong binding to Fe(III) and facile release of Fe(II) when the metal center is reduced. It should be noted that the cellular uptake of 1 is not transferrin receptor-mediated but enhanced by the high lipophilicity of chlorquinaldol. Once 1 is transported across the cell membrane, Fe(III) can be reduced by ferric reductase or other cellular antioxidants to be released as Fe(II), which triggers the Fenton catalytic reaction, thus harnessing the anticancer activity of iron. As the result, this transferrin-inspired iron-delivery strategy significantly reduces the cytotoxicity of 1 in normal human embryonic kidney cells (HEK 293) and the hemolytic activity of 1 in human red blood cells (hRBCs), giving rise to the unique tumor-specific anticancer activity of this Fe(III) complex. [ABSTRACT FROM AUTHOR]

Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study's findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels. [ABSTRACT FROM AUTHOR]

Background: The anemia prevalence is higher in highlands populations. It is assumed that iron deficiency anemia (IDA) in children is mainly due to low dietary intake. However, other suggest that high prevalence of anemia is due to an inappropriate hemoglobin (Hb) adjustment for altitude. Materials and methods: Cross-sectional study conducted in 338 preschoolers (PSC) from Puno-Peru. Hb was measured in whole blood, and ferritin, Soluble transferrin receptor, and Interleukin 6 in serum.The dietary iron intake was assessed by 24-h dietary recall, using NutriCap Software. Hb concentration was assessed as adjusted or unadjusted for altitude. Results: With unadjusted Hb, the anemia prevalence was 4.7%, whereas after Hb correction, the prevalence raised-up to 65.6% (p < 0.001). Reciprocally, erythrocytosis proportion decreased from 20.35 to 0.30% (p < 0.001). Total Body Iron (TBI) showed that 7.44% had ID and 0.32% had IDA. PSC with normal unadjusted Hb levels have more protein and micronutrients intake than anemic ones. PSC with erythrocytosis consumed less fat, and more niacin and ascorbic acid than anemics. Total iron intake was lower in anemic than the other groups, but without statistical significance due to the standard deviation of the data in a small number of anemic PSC (n = 16). TBI, unadjusted Hb, and adjusted Hb were not different between groups consuming or not multimicronutrients. Conclusions: The consumption of iron and iron status in children who live at high altitude is adequate, and that anemia could be due to other micronutrient deficiencies and/or that the adjustment of Hb by altitude is inappropriate. [ABSTRACT FROM AUTHOR]

Introduction: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret‐He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort. Methods: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret‐He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret‐He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret‐He in ID, IDA, and anemia without ID groups. Results: Ret‐He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret‐He was significantly lower in ID. A Ret‐He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret‐He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively. Conclusion: Our large pediatric tertiary care hospital study demonstrates that Ret‐He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of iron in the substantia nigra. While iron accumulation and inflammation are implicated in PD pathogenesis, their impact on oligodendrocytes, the brain's myelin-forming cells, remains elusive. This study investigated the influence of interleukin-1β (IL-1β), an elevated proinflammatory cytokine in PD, on iron-related proteins in MO3.13 oligodendrocytes. We found that IL-1β treatment in undifferentiated MO3.13 oligodendrocytes increased iron regulatory protein 1 and transferrin receptor 1 (TfR1) expression while decreasing ferroportin 1 (FPN1) expression. Consequently, iron uptake was enhanced, and iron release was reduced, leading to intracellular iron accumulation. Conversely, IL-1β treatment in differentiated MO3.13 oligodendrocytes exhibited the opposite effect, with decreased TfR1 expression, increased FPN1 expression, and reduced iron uptake. These findings suggest that IL-1β-induced dysregulation of iron metabolism in oligodendrocytes may contribute to the pathological processes observed in PD. IL-1β can increase the iron content in undifferentiated oligodendrocytes, thus facilitating the differentiation of undifferentiated MO3.13 oligodendrocytes. In differentiated oligodendrocytes, IL-1β may facilitate iron release, providing a potential source of iron for neighboring dopaminergic neurons, thereby initiating a cascade of deleterious events. This study provides valuable insights into the intricate interplay between inflammation, abnormal iron accumulation, and oligodendrocyte dysfunction in PD. Targeting the IL-1β-mediated alterations in iron metabolism may hold therapeutic potential for mitigating neurodegeneration and preserving dopaminergic function in PD. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Neurological Surgery, examines the diagnostic accuracy of beta-2 transferrin gel electrophoresis (B2Tf GE) in detecting cerebrospinal fluid (CSF) rhinorrhea. The study conducted a retrospective review of patients who presented with unilateral thin clear rhinorrhea (UTCR) and underwent B2Tf GE. The results showed that B2Tf GE had a sensitivity of 87.5%, specificity of 76.9%, positive predictive value of 77.8%, and negative predictive value of 87% in detecting CSF rhinorrhea. However, the study also highlighted the potential limitations of B2Tf GE and suggested considering other diagnostic tests in cases where B2Tf GE results deviate from clinical suspicion. [Extracted from the article]

In people with a hereditary predisposition, gluten consumption causes celiac disease, a multifactorial autoimmune condition. The ensuing small intestine inflammatory process develops specific antibodies and causes various gastrointestinal and extra-intestinal symptoms with varying degrees of severity. Evaluation of the blood iron profile at various histological celiac disease severity in Iraqi patients was the goal of the current study. Seventy-five Iraqi patients with celiac disease, with a mean age of 18.68± 11.13 years, were the study's participants. These people tested positive for celiac antibodies and experienced gastrointestinal symptoms. Based on the disease histological severity, they were divided into two groups: marsh (III a, b, c) group and marsh (0, I) group. For comparison purposes, 46 people who appeared to be in good health and matched in age and gender to the patients utilized in the study were also included. The levels of iron, transferrin, hemoglobin, ferritin, total iron binding capacity, unsaturated iron binding capacity, and the percentage of transferrin that is saturated with iron were all measured. In comparison to the other patient groups under study, celiac patients (marsh III) group, and particularly those of group (marsh III c), showed a substantial drop (p<0.05) in iron, the percentage of transferrin saturating with iron, the levels of each ferritin and of hemoglobin. The total iron binding capacity and the unsaturated iron binding capacity showed a significant elevation (p<0.05) in (marsh III c) patients' group, meanwhile non-significant differences (p> 0.05) were found in transferrin concentration. Moreover, significant differences (p< 0.05) were obtained in the iron profile between celiac patients who followed strict gluten free diet and those patients with gluten contained diet. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10–14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale–Long Form, Parent Rating Scales Revised–Short Form, and Teacher Rating Scales Revised–Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [&#946= 0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (&#946= 0.04; 95% CrI: 0.00, 0.08), and 4.1% (β= 0.04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. [ABSTRACT FROM AUTHOR]

Endo-β- N -acetylglucosaminidases (ENGases) are enzymes that hydrolyze N -linked glycans. Many ENGases have been characterized, but few have been identified with hydrolytic activity towards multi-branched complex-type N -glycans. In this study, three candidate ENGases were identified from Barnesiella intestinihominis based on database searches and phylogenetic analysis. A domain search identified the N x E motif in all three candidates, suggesting that they were members of glycosyl hydrolase family 85 (GH85). The three candidate ENGases, named Endo-BIN1, Endo-BIN2, and Endo-BIN3, were expressed in Escherichia coli cells, and their hydrolytic activity towards N -glycans and glycoproteins was measured by high performance liquid chromatography analysis and SDS-PAGE analysis. All ENGases showed hydrolytic activity towards glycoproteins, but only Endo-BIN2 and Endo-BIN3 showed hydrolytic activity towards pyridylaminated N -glycans. The optimum pH of Endo-BIN1, Endo-BIN2, and End-BIN3 was pH 6.5, 4.0, and 7.0, respectively. We measured substrate specificities of Endo-BIN2 and Endo-BIN3 towards pyridylaminated N -glycans, and found that the two Endo-BIN enzymes showed similar substrate specificity, preferring bi-antennary complex-type N -glycans with galactose or α2,6-linked sialic acid residues at the non-reducing ends. Endo-BIN2 and Endo-BIN3 were also able to hydrolyze multi-branched complex-type N -glycans. SDS-PAGE analysis revealed that all Endo-BIN enzymes were capable of releasing complex-type N -glycans from glycoproteins such as rituximab, transferrin, and fetuin. We expect that B. intestinihominis possesses ENGases to facilitate the utilization of complex-type N -glycans from host cells. These findings will have applications in N -glycan remodeling of glycoproteins and the development of pharmaceuticals. [ABSTRACT FROM AUTHOR]

The dysregulation of iron metabolism is closely linked to the onset and progression of lung cancer. This study aimed to explore the association between iron metabolism indicators (serum iron, transferrin, ferritin) and the expression level of programmed death factor ligand 1 in primary lesions of advanced non-small cell lung cancer. A cohort of 62 patients, including 42 men and 20 women, was recruited from October 2022 to July 2023, all diagnosed with advanced non-small cell lung cancer, confirmed through radiographic imaging and histopathological analysis. Comprehensive clinical data (such as gender, age, familial lung cancer history, smoking history, pathological classification, clinical stage, etc.) and concentrations of fasting serum iron, transferrin, and ferritin were collected. Patients were categorized into PD-L1 negative (<1% expression) and programmed death ligand 1 (PD-L1) positive (-1% expression) groups based on PD-L1 expression levels in tumor tissues. Subsequently, the correlation between levels of serum iron, transferrin, ferritin, and PD-L1 expression in advanced non-small cell lung cancer were examined. Patients in the PD-L1 positive group exhibited lower levels of peripheral serum iron and transferrin compared to those in the PD-L1 negative group (P<0.05). For patients exhibiting positive PD-L1 expression, a negative correlation was observed between PD-L1 expression and both serum iron and transferrin levels (r = -0.465, P=0.003; r = -0.447, P=0.005), and a positive correlation was noted between PD-L1 expression and ferritin levels (r=0.393, P=0.015). We conclude that in In patients with advanced nonsmall cell lung cancer, serum iron and transferrin levels can serve as partial predictors of PD-L1 expression; among those positive for PD-L1, a significant association exists between indicators of iron metabolism and PD-L1 expression. [ABSTRACT FROM AUTHOR]

Background: The research aimed to analyze blood biochemical parameters in patients with amyotrophic lateral sclerosis and to determine whether they can be used to assess their nutritional status. Methods: The study included 45 patients diagnosed with amyotrophic lateral sclerosis (ALS): 28 (62.2%) were men and 17 (37.8%) were women. The mean age of the study participants was 50.69 ± 7.24 years. The control group consisted of 30 practically healthy individuals. Results: Compared with practically healthy individuals, patients with ALS had significantly lower blood parameters, including total lymphocyte count (1.49 ± 0.11 vs. 2.86 ± 0.25, p < 0.05), total protein (60.55 ± 2.38 vs. 77.80 ± 4.41, p < 0.05), albumin (33.70 ± 2.03 vs. 46.49 ± 3.22, p < 0.05), urea (3.09 ± 0.36 vs. 5.37 ± 0.50, p < 0.05), creatinine (51.28 ± 4.42 vs. 70.91 ± 5.13, p < 0.05), and transferrin (1.84 ± 0.12 vs. 2.32 ± 0.10, p < 0.05). These parameters correspond to first-degree malnutrition. There were direct correlations between anthropometric and biochemical parameters in the ALS group. BMI correlated with the blood levels of total protein (r = 0.22, p < 0.05), albumin (r = 0.27, p < 0.05), urea (r = 0.33, p < 0.05), creatinine (r = 0.30, p < 0.05), transferrin (r = 0.18, p < 0.05), and total lymphocyte count (r = 0.20, p < 0.05). PNI correlated with the blood levels of total protein (r = 0.53, p < 0.05), albumin (r = 0.87, p < 0.05), total cholesterol (r = 0.34, p < 0.05), transferrin (r = 0.40, p < 0.05), total lymphocyte count (r = 0.79, p < 0.05), urea (r = 0, 37, p < 0.05), and creatinine (r = 0.32, p < 0.05). Conclusion: The study presents compelling evidence supporting the utilization of biochemical parameters, including total protein, albumin, urea, creatinine, transferrin, and total lymphocyte count, for potentially evaluating the nutritional status of individuals diagnosed with ALS. [ABSTRACT FROM AUTHOR]

Standard clinical markers can improve tick-borne infection (TBI) diagnoses. We investigated immune and other clinical biomarkers in 110 patients clinically diagnosed with TBIs before (T0) and after antibiotic treatment (T2). At T0, both the initial observation group and patients without seroconversion for tick-borne pathogens exhibited notably low percentages and counts of CD3 percentage (CD3%), CD3+ cells, CD8+ suppressors, CD4 percentage (CD4%), and CD4+ helper cells, with the latter group showing reductions in CD3%, CD3+, and CD8+ counts in approximately 15-22% of cases. Following treatment at the T2 follow-up, patients typically experienced enhancements in their previously low CD3%, CD3+ counts, CD4%, and CD4+ counts; however, there was no notable progress in their low CD8+ counts, and a higher number of patients presented with insufficient transferrin levels. Moreover, among those with negative serology for tick-borne infections, there was an improvement in low CD3% and CD3+ counts, which was more pronounced in patients with deficient transferrin amounts. Among those with CD57+ (n = 37) and CD19+ (n = 101) lymphocyte analysis, 59.46% of patients had a low CD57+ count, 14.85% had a low CD19 count, and 36.63% had a low CD19 percentage (CD19%). Similar findings were observed concerning low CD57+, CD19+, and CD19% markers for negative TBI serology patients. Overall, this study demonstrates that routine standard clinical markers could assist in a TBI diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: About 94% of oral cancers are squamous cell carcinomas (OSCCs). Its occurrence is age‐related due to some factors. Salivary biomarkers have good susceptibility to OSCC's early diagnosis. Moreover, since the clinical diagnosis of advanced stages of OSCC is feasible, its prognosis is very poor. Material and Methods: According to inclusion and exclusion criteria, 40 OSCC patients and 40 healthy people were selected, and 5 mL of saliva were prepared from each person. The quantity of saline transferrin was computed. After that, the data were analyzed. Results: Our study results demonstrated that the mean and standard deviation of the salivary transferrin in the control group were 1.234 mL and 0.374, respectively, and in the case group, it was equal to 2.512 mL for the mean and 0.463 for the standard deviation. There was a statistically substantial difference between the mean of the salivary transferrin variable in the two study groups. Conclusion: In conclusion, the mean concentration of salivary transferrin in the case group was higher than in the control group. [ABSTRACT FROM AUTHOR]

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

Background: High-sensitive cardiac troponin T (h-cTnT), which serves as a marker for myocardial damage, has also been linked to adverse outcomes in asymptomatic hemodialysis patients. This study aims to explore the correlation between interleukin-6 (IL-6) and h-cTnT in asymptomatic hemodialysis patients to unravel the relationship between inflammation and cardiovascular risk. Methods: A cross-sectional study involving 81 patients was conducted from November 2022 to March 2023 at An-Najah National University Hospital in Palestine. We gathered clinical data, including comorbidities, and obtained blood samples for measuring IL-6 and h-cTnT levels. We performed statistical analyses, including correlation tests and linear regression, to assess the associations between these variables. Results: The study revealed a notable increase in both h-cTnT and IL-6 levels, and a significant correlation between the two (rho = 0.463, P<0.001) in asymptomatic hemodialysis patients. Likewise, h-cTnT levels displayed positive correlations with age (rho = 0.519, P<0.001) and negative correlations with albumin (rho = -0.297, p = 0.007) and transferrin saturation (rho = -0.227, P = 0.042). IL-6 levels exhibited correlations with age (rho = 0.422, P<0.001), albumin (rho = -0.389, P<0.001), iron (rho = -0.382, P<0.001), and transferrin saturation (rho = -0.362, P = 0.001). Notably, higher h-cTnT levels were associated with diabetes, hypertension, a history of coronary artery disease, cerebrovascular accidents, older age, and male gender. Conclusion: This study underscores the significant association between the inflammatory marker IL-6 and h-cTnT in asymptomatic hemodialysis patients, suggesting that inflammation may play an essential role in the elevation of h-cTnT levels. This association may have implications for predicting cardiovascular events and guiding interventions to reduce cardiovascular disease morbidity and mortality in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Some bioactive substances in food have problems such as poor solubility, unstable chemical properties and low bioavailability, which limits their application in functional food. Recently, many egg white protein-based delivery carriers have been developed to improve the chemical stability, biological activity and bioavailability of bioactive substances. This article reviewed the structure and properties of several major egg white proteins commonly used to construct bioactive substance delivery systems. Several common carrier types based on egg white proteins, including hydrogels, emulsions, micro/nanoparticles, aerogels and electrospinning were then introduced. The biological functions of common bioactive substances, the limitations, and the role of egg white protein-based delivery systems were also discussed. At present, whole egg white protein, ovalbumin and lysozyme are most widely used in delivery systems, while ovotransferrin, ovomucoid and ovomucin are less developed and applied. Egg white protein-based nanoparticles are currently the most commonly used delivery carriers. Egg white protein-based hydrogels, emulsions, and microparticles are also widely used. Future research on the application of various egg white proteins in developed new delivery systems will provide more choices for the delivery of various bioactive substances. [ABSTRACT FROM AUTHOR]

Chronic suppurative otitis media (CSOM) is a prevalent chronic inflammatory disease globally. Current research suggests a possible association between anaemia and the development of CSOM. The objective of this trial was to investigate the relationship between iron metabolism and chronic suppurative otitis media (CSOM) in adults aged 20–60 years. A consecutive sampling case-control study was used. The study participants were divided into a case group (42 children diagnosed with CSOM) and a control group (42 children with normal ears). Haemoglobin (Hb), Hematocrit (Hct), mean corpuscular volume of erythrocytes (MCV), serum iron level (SI), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin (TF), ferritin (Fer) were tested in all the participants, and the results were compared with the normal ranges of the World Health Organization (WHO). The comparative analysis of cases and controls was performed using the Fisher extract test, independence t-test, or Mann–Whitney U test. p-value <.05 was considered statistically significant for correlation. There were 61 patients with CSOM and 61 controls included in the study. In the case group, 16 out of 61 patients (26.2%) had low ferritin levels and in the control group, 1 out of 61 patients (1.6%) had low ferritin levels (p <.001). In the case group, 6 (9.8%) of 61 patients had IDA, and in the control group, there were no patients with IDA among 61 patients (p =.027). There were significant differences in SI, UIBC, and Fer parameters between the groups. In adult patients, the incidence of iron deficiency was higher in CSOM patients than in controls. Iron deficiency may be considered a potential risk factor for chronic suppurative otitis media, and serum iron parameters should be evaluated in these CSOM patients and further studies should be conducted to better understand the potential link between iron deficiency and CSOM. [ABSTRACT FROM AUTHOR]

The present study compared the effectiveness of insulin plus liraglutide or dapagliflozin in treating type 2 diabetes mellitus complicated with metabolic syndrome and observed the nutritional status of patients before and after treatment. The results revealed no significant difference in the overall clinical efficacy and blood glucose levels between the liraglutide group treated with liraglutide and the dapagliflozin group treated with dapagliflozin (P > 0.05). In contrast, the adverse reactions in the liraglutide group were even lower than those in the control group (P < 0.05). In addition, the liraglutide group demonstrated better improvements in insulin metabolism and blood lipid levels than the dapagliflozin group after treatment. However, their ability to repair thyroid function and alleviate oxidative stress was comparatively weak (P < 0.05). Serum albumin, total protein, and transferrin levels were elevated in both groups after treatment, but the increase in the dapagliflozin group was higher than that in the liraglutide group (P < 0.05). The number of malnutrition cases was significantly reduced in both groups after treatment compared to before treatment (P < 0.05). These results suggest that the combination of insulin with liraglutide or dapagliflozin is highly effective in treating type 2 diabetes mellitus complicated by metabolic syndrome and can effectively improve the nutritional status of patients. [ABSTRACT FROM AUTHOR]

In this study, we compared the clinical outcomes and differences in nutritional status between preschool and postsurgical treatment of intermittent exotropia. We selected 100 children with intermittent exotropia between August 2019 and August 2022 for the study. Among them, 42 children received surgical treatment before school age (4-6 years) and were considered to be in group A, whereas 58 children received surgical treatment after school age (7-12 years) and were considered to be in group B. We found no difference in orthokeratology, overcorrection, or undercorrection rates between the two groups of children before and after surgery (P > 0.05), and the strabismus was lower at 6 and 12 months after surgery than before surgery and lowest at 12 months after surgery (P < 0.05). In addition, the normal rates of visual function, fusion function, and binocular stereopsis were higher in group A than in the control group at 6 and 12 months postoperatively (P < 0.05). The Child Intermittent Exotropia Questionnaire scores were higher in both groups at 12 months postoperatively than at 6 months and were higher in group A than in group B (P < 0.05). Family members of children in group A were more satisfied with the treatment than in group B (P < 0.05), but the difference in albumin, transferrin, and proalbumin before and after surgery was lower in group B than in group A (P < 0.05). It follows that performing intermittent exotropia surgery before school age can more effectively improve the prognosis of children's binocular visual function, whereas performing intermittent exotropia after school age has less impact on nutritional status. [ABSTRACT FROM AUTHOR]

Preterm labor, one of the common pathological phenomena during pregnancy, necessitates prompt and accurate detection to safeguard the health of both pregnant women and newborns. This study focused on placental alkaline phosphatase, a pregnancy-specific enzyme, and its potential role in identifying preterm labor. This study aimed to investigate the relationship between placental alkaline phosphatase, placental maturity, the nutritional status of newborns, and its utility in evaluating preterm labor. A total of 85 pregnant women with singleton pregnancy of more than 15 weeks of gestation admitted to our hospital from March 2022 to May 2023 were selected as study subjects. Our study revealed a positive correlation between PLAP levels and both gestational age and placental maturity (P < 0.05). Our findings indicated that with an increase in gestational age and placental maturity, there was a corresponding increase in placental alkaline phosphatase levels. However, there were no differences in placental alkaline phosphatase between pregnant women of Grade III and Grade II in terms of placental maturity (P > 0.05). There was a significant increase in placental alkaline phosphatase levels among pregnant women who gave birth prematurely (P < 0.05). The receiver operating characteristic curve showed that placental alkaline phosphatase had an excellent effect on the evaluation of preterm labor (P < 0.05). However, there were no significant differences in placental alkaline phosphatase between the pregnant women with and without postpartum complications (P > 0.05). Lastly, placental alkaline phosphatase was found to have an inverse relationship with levels of neonatal albumin and transferrin levels (P < 0.05). [ABSTRACT FROM AUTHOR]

Introduction: Malnutrition is a global phenomenon and may be contributing to the increasing size of the hemodialysis (HD) population in South Africa and is affecting morbidity and clinical outcomes. Our study assessed whether transferrin could be a possible marker for malnutrition in the HD population. Methods: Clinical parameters (including skinfold thickness and mid-upper arm circumference [MUAC]) and laboratory markers (including transferrin and hemoglobin) were measured during a six-month period in a sample of 59HD patients. Results: Linear regression analysis showed that MUAC (p=0.027) as well as skinfold thickness (p=0.021) had a significant association with transferrin levels within the HD participants. There was no significant association between transferrin levels or MUAC with hemoglobin levels (p=0.075). Furthermore, the study found that decreased transferrin levels (< 2.15g/dL to 3.80g/dL) were closely related to malnutrition in the malnutrition distribution groups within the study, with 97.7% of HD participants being classified in one of the malnutrition groups. Conclusion: Thus, transferrin levels are a valuable marker for malnutrition within the HD patient population and can be included along with clinical assessment parameters such as MUAC and skinfold thickness as primary indicators for malnutrition. [ABSTRACT FROM AUTHOR]

The pathogenesis of Autoimmune Hepatitis (AIH) is closely associated with perturbations in iron ion metabolism, during which Stimulator of Interferon Genes (STING) plays an important role. However, the precise regulatory mechanism remains elusive. In this study, we investigated the relationship between iron dysregulation and STING activation in Concanavalin A (ConA)-induced AIH liver injury. STING knockout (STING−/−) mice and AAV (Adeno-Associated virus)-Sting1-RNAi-treated mice were involved and subjected in AIH. We observed that increased iron dysregulation was linked with STING activation, but this effect was effectively reversed by the administration of iron chelating agent Desferoxamine (DFO) and the antioxidant Ferrostatin-1 (Fer-1). Notably, the iron transport protein Transferrin (TF) and Transferrin Receptor (TfR) exhibited significant accumulation in AIH along with upregulated expression of ferritin protein. Additionally, the deficiency of STING reduced hepatic iron accumulation, mitigated oxidative stress, and attenuated macrophage activation during ConA treatment. Furthermore, liver-specific knockdown of STING using AAV-Sting1-RNAi significantly ameliorated liver iron dysregulation and oxidative stress response induced by Kupffer cells (KCs). KC-derived STING exacerbates liver damage severity in AIH through promoting disturbances in hepatic iron ion metabolism as well as oxidative stress response. These findings provide valuable insights into the pathogenesis of AIH and may pave the way for potential therapeutic strategies targeting STING and iron metabolism in the future. [Display omitted] • Iron dysregulation contributes to the ConA-induced hepatic injury. • STING deficiency attenuated liver injury accompanied with reduction of iron overload. • Macrophage STING serves as a key regulator for triggering iron dysregulation and further leading to necrotic damage in AIH. [ABSTRACT FROM AUTHOR]

Type 2 Diabetes (T2DM) has been linked to ferroptosis. This study aimed to assess expression levels of genes linked with iron metabolism in peripheral blood mononuclear cells (PBMCs) from T2DM patients and to investigate the association of these expression levels with anthropometric and clinical parameters. Gene expression of iron metabolism genes (Ferritin Light Chain , FTL; Ferritin Heavy Chain, FTH1; Transferrin Receptor, TFRC; Divalent Metal Transporter 1, SLC11A2; Ferroportin, SLC40A1) in archival PBMCs was assessed using quantitative real-time PCR assays. Correlations of gene expression with anthropometric/biochemical patient data were evaluated. The study included 36 (18 male/18 female) T2DM patients and 45 (28 male/17 female) normoglycemic (NGT) subjects with a mean age of 38.1 ± 6.8 years and 47.6 ± 8.6 years respectively. Relative expression of FTL was significantly lower in T2DM females compared to that in NGT females (P = 0.027). Relative expression of SLC40A1 was significantly lower in the T2DM group (P = 0.043) and in the T2DM females (P = 0.021). Relative expression of SLC11A2 was negatively correlated with systolic blood pressure in T2DM male patients. Relative expression of SLC40A1 was negatively associated with serum phosphorous and positively associated with serum thyroid stimulating hormone in male T2DM patients. Our findings indicate a reduction in the expression of FTL in perimenopausal T2DM females. Also, in male T2DM patients and NGT subjects, biochemical markers are significantly correlated with the expression of FTL , FTH1 , SLC11A2 , and SLC40A1 in PBMCs. [Display omitted] [ABSTRACT FROM AUTHOR]

Adequate and timely delivery of iron is essential for brain development. The uptake of transferrin‐bound (Tf) iron into the brain peaks at the time of myelination, whereas the recently discovered H‐ferritin (FTH1) transport of iron into the brain continues to increase beyond the peak in myelination. Here, we interrogate the impact of dietary iron deficiency (ID) on the uptake of FTH1‐ and Tf‐bound iron. In the present study, we used C57BL/6J male and female mice at a developing (post‐natal day (PND) 15) and adult age (PND 85). In developing mice, ID results in increased iron delivery from both FTH1 and Tf for both males and females. The amount of iron uptake from FTH1 was higher than the Tf and this difference between the iron delivery was much greater in females. In contrast, in the adult model, ID was associated with increased brain iron uptake by both FTH1 and Tf but only in the males. There was no increased uptake from either protein in the females. Moreover, transferrin receptor expression on the microvasculature as well as whole brain iron, and H and L ferritin levels revealed the male brains became iron deficient but not the female brains. Last, under normal dietary conditions, 55Fe uptake was higher in the developing group from both delivery proteins than in the adult group. These results indicate that there are differences in iron acquisition between the developing and adult brain for FTH1 and Tf during nutritional ID and demonstrate a level of regulation of brain iron uptake that is age and sex‐dependent. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common complication of chronic kidney disease (CKD) and oral iron is recommended as initial therapy. However, response to iron therapy in children with non-dialysis CKD has not been formally assessed. Methods: We reviewed medical records of pediatric patients with stages II–IV CKD followed in two New York metropolitan area medical centers between 2010 and 2020 and identified subjects who received oral iron therapy. Response to therapy at follow-up visits was assessed by improvement of hemoglobin, resolution of anemia by the 2012 KDIGO definition, and changes in iron status. Potential predictors of response were examined using regression analyses (adjusted for age, sex, eGFR, and center). Results: Study criteria were met by 65 children (median age 12 years, 35 males) with a median time between visits of 81 days. Median eGFR was 44 mL/min/1.73 m2, and 40.7% had glomerular CKD etiology. Following iron therapy, hemoglobin improved from 10.2 to 10.8 g/dL (p < 0.001), hematocrit from 31.3 to 32.8% (p < 0.001), serum iron from 49 to 66 mcg/dL (p < 0.001), and transferrin saturation from 16 to 21.4% (p < 0.001). There was no significant change in serum ferritin (55.0 to 44.9 ng/mL). Anemia (defined according to KDIGO) resolved in 29.3% of children. No improvement in hemoglobin/hematocrit was seen in 35% of children, and no transferrin saturation improvement in 26.9%. There was no correlation between changes in hemoglobin and changes in transferrin saturation/serum iron, but there was an inverse correlation between changes in hemoglobin and changes in ferritin. The severity of anemia and alkaline phosphatase at baseline inversely correlated with treatment response. Conclusions: Anemia was resistant to 3 months of oral iron therapy in ~ 30% of children with CKD. Children with more severe anemia at baseline had better treatment response, calling for additional studies to refine approaches to iron therapy in children with anemia of CKD and to identify additional predictors of treatment response. [ABSTRACT FROM AUTHOR]

Objective: The level of immunological reactivity of the indigenous inhabitants of the Far North may depend on the extreme‐discomfort factors of the climatic environment and genetic traits of the population. Therefore, the aim of this study was to identify the distinctive elements of the immune status of the Kola Saami and Russians living in the Far North (Murmansk Region). Methods: A complex immunological study of peripheral venous blood composition was performed and involved 67 Saami and 81 Russian inhabitants of the Far North (Murmansk Region) who were aged 21–55. Blood was collected from the cubital vein on an empty stomach in the morning. For the peripheral venous blood, we obtained a hemogram and phagocytic activity of neutrophils, determined the content of lymphocytes with CD4, CD8, CD16, and CD71 phenotypes by indirect immunoperoxidase reaction and flow cytometry using an Epics XL apparatus (Beckman Coulter, United States), obtained concentrations of IL‐6, IFN‐γ, IL‐10, IgA, M, G, E, sCD54, and sCD62L, transferrin, and sCD71 by enzyme immunoassay using the "Evolis" enzyme immunoassay analyzer from Bio‐RAD (Germany), and obtained circulating immune complexes by precipitation using 3.5%, 4.0%, and 7.5% PEG‐6000. The sIgA content was determined in morning saliva, urine, and gastrointestinal tract secretions. The results were analyzed using descriptive statistics, independent sample t‐criterion, and Pearson correlation coefficient. Results: A decrease in the total number of leukocyte cells in the Saami was associated with a high incidence of leukopenia, lymphopenia, and neutropenia. Deficiency in active phagocytes and serum IgA and sIgA concentrations was revealed as well as increased contents of CD4+ and CD8+ receptor lymphocytes, membrane and free adhesion molecules, and transferrin. Leukocytosis, lymphocytosis, neutrophilia, monocytosis, and eosinophilia with increased contents of natural killer cells, IL‐6, and IL‐10 were recorded more frequently in the Russians. High levels of IgE and IFN‐γ, which have the most pronounced cytotoxicity and are indicative of strained immune mechanisms, were characteristic of the Saami and Russians. Conclusion: The distinctive aspects of the immune status of the Kola Saami is related to the deficit in the active phagocyte and serum IgA and sIgA concentrations as well as the increase in the contents of cytotoxic lymphocytes, intercellular adhesion molecules, transferrin, and IFN‐γ proinflammatory cytokines. The Russian inhabitants of the Far North are characterized by an adaptive response manifested by an increase in antibody‐dependent cytotoxicity, involving IL‐6 and IL‐10. [ABSTRACT FROM AUTHOR]

Ferroptosis and necroptosis are recognized as playing major roles in the regulation of various physiological processes. However, the physiological role of the cell death mediated by these two pathways in the developmental process has not yet been clearly established. This study investigated ferroptosis and necroptosis signalling pathways in maternal–fetal tissue in the different gestational days (GD) of rat pregnancy using immunohistochemical and western blot methods in order to fill this gap. Twenty‐four female Wistar albino rats were mated and divided into three groups. Maternal–fetal tissue samples were collected on GD 5, 12 and 19 of pregnancy. Expression and total protein levels of the markers glutathione peroxidase‐4, soluble transporter family 7 member 11, transferrin receptor, receptor‐interacting serine/threonine‐protein kinase 1, receptor‐interacting serine/threonine‐protein kinase 3 and mixed lineage kinase domain‐like protein were investigated on both the maternal and fetal surfaces of the placenta using immunohistochemical and western blot methods. The results showed varying levels of protein expression of both ferroptosis and necroptosis mediators in the GD 5, 12 and 19 of pregnancy. Immunohistochemical analyses revealed that these mediators were located on both the maternal (decidua and metrial gland) and fetal surfaces (labyrinth zone, yolk sac and basal zone) and that their expression levels changed in the different GD. The findings revealed the existence of important ferroptosis and necroptosis pathway mediators in rat maternal–fetal tissue. These results may provide a molecular framework for a better understanding of the communication between the placenta, decidua and fetus during the developmental process. [ABSTRACT FROM AUTHOR]

Frequent phlebotomies, even when only a small volume of blood is taken for diagnostic purposes, can lead to the development of iron deficiency with hematological and metabolic changes. The study aimed to determine the influence of frequent blood loss by phlebotomy on blood iron concentration (Fe), hematology, metabolic and endocrine parameters and their relationships. Blood samples were collected from 30 blood donor rams for 6 consecutive weeks, with approximately 10% of blood collected weekly. Such chronic blood loss resulted in a decrease in Fe. Indicators of iron transport in the bloodstream changed, so the value of total iron-binding capacity (TIBC) and unsaturated iron-binding capacity (UIBC) increased, while the value of transferrin saturation percentage (TS%) decreased. Hematological changes included a decrease in red blood cells, hemoglobin, mean red blood cell volume and hematocrit and a tendency for reticulocyte count and red cell distribution width to increase. Chronic blood loss resulted in a specific metabolic response that included the increase in glucose, cholesterol, triglycerides, aspartate-aminotransferase, and insulin resistance, while thyroxine, triiodothyronine and cortisol decreased and there was a tendency for lactate to increase and BHB to decrease. The mentioned blood parameters correlated with Fe and additionally showed greater changes when Fe was extrapolated to the level of clinical deficit (Fe=9μmol/L). These correlations suggest the need to monitor the metabolic and endocrine status during chronic blood loss, in addition to Fe and erythrocyte indices. Compared with previous results in other animal species, Fe may have a direct influence on metabolic processes in rams. [ABSTRACT FROM AUTHOR]

Secretory otitis media (SOM) is a clinical condition characterized by the accumulation of fluids and oxidative stress in the middle ear, leading to hearing impairment and infection complications. One potential solution for mitigating oxidative stress associated with SOM is the use of antioxidants such as astaxanthin. However, its effectiveness is limited due to its poor bioavailability and rapid oxidation. Herein, we developed a novel diselenium-crosslinked apotransferrin enriched with astaxanthin (AST@dSe-AFT) nanoparticles to augment the transport of astaxanthin across biological membranes, resulting in increased bioavailability and reduced oxidative stress in SOM. Our research demonstrated that AST@dSe-AFT efficiently accumulated in the middle ear, allowing for controlled delivery of astaxanthin in response to reactive oxygen species and reducing oxidative stress. Additionally, AST@dSe-AFT stimulated macrophages to polarize towards M2 phenotype and neutrophils to polarize towards N2 phenotype, thereby facilitating an anti-inflammatory response and tissue restoration. Importantly, AST@dSe-AFT exhibited no toxicity or adverse effects, suggesting its potential for safety and future clinical translation. Our findings suggested that AST@dSe-AFT represents a promising approach for the treatment of secretory otitis media and other oxidative stress-related disorders. The ROS-responsive nanoparticles AST@dSe-AFT exhibited outstanding ROS/RNS scavenging ability as well as inflammation inhibitory effect by degrading diselenium bond to release AST. [Display omitted] • A self-assembly of AFT and diselenium was employed for encapsulating and delivering AST. • AST@dSe-AFT demonstrates responsive release of AST, specifically triggered by ROS in the inflammatory microenvironment. • AST@dSe-AFT exhibits potent anti-inflammatory and antioxidant activity in a SOM model. [ABSTRACT FROM AUTHOR]

Background Diagnosing iron deficiency is challenging in the presence of systemic inflammation. Aim To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome. Design Test prospective cohort and validation retrospective cohort. Methods A prospective cohort of inpatients (n  = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n  = 795) further assessed the predictive power of this ratio. Results In a training cohort (median age 76 years [57–84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57–84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85–0.90], with an odds ratio of 37.9 [95% CI: 20.3–68.9] for the threshold of ≤6. Conclusion In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies. [ABSTRACT FROM AUTHOR]