Transferrin levels are associated with malnutrition markers in hemodialysis patients in KwaZulu-Natal, South Africa.

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 59 HD 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 (< 2.15 g/dL to 3.80 g/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.

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem.

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a groundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.

A conserved asparagine residue stabilizes iron binding in Manduca sexta transferrin-1.

Transferrin 1 (Tsf1) is an insect-specific iron-binding protein that is abundant in hemolymph and other extracellular fluids. It binds iron tightly at neutral pH and releases iron under acidic conditions. Tsf1 influences the distribution of iron in the body and protects against infection. Elucidating the mechanisms by which Tsf1 achieves these functions will require an understanding of how Tsf1 binds and releases iron. Previously, crystallized Tsf1 from Manduca sexta was shown to have a novel type of iron coordination that involves four iron-binding ligands: two tyrosine residues (Tyr90 and Tyr204), a buried carbonate anion, and a solvent-exposed carbonate anion. The solvent-exposed carbonate anion was bound by a single amino acid residue, a highly conserved asparagine at position 121 (Asn121); thus, we predicted that Asn121 would be essential for high-affinity iron binding. To test this hypothesis, we analyzed the iron-binding and -release properties of five forms of recombinant Tsf1: wild-type, a Y90F/Y204F double mutant (negative control), and three Asn121 mutants (N121A, N121D and N121S). Each of the Asn121 mutants exhibited altered spectral properties, confirming that Asn121 contributes to iron coordination. The N121D and N121S mutations resulted in slightly lower affinity for iron, especially at acidic pH, while iron binding and release by the N121A mutant was indistinguishable from that of the wild-type protein. The surprisingly minor consequences of mutating Asn121, despite its high degree of conservation in diverse insect species, suggest that Asn121 may play a role that is essential in vivo but non-essential for high affinity iron binding in vitro.

Proteomic Analysis of Egg Yolk Proteins During Embryonic Development in Wanxi White Goose.

To investigate the alterations of yolk protein during embryonic development in Wanxi white goose, the egg yolk protein composition at days 0, 4, 7, 14, 18, and 25 of incubation (D0, D4, D7, D14, D18, and D25) was analyzed by two-dimensional gel electrophoresis combined with mass spectrometry. A total of 65 spots representing 11 proteins with significant abundance changes were detected. Apolipoprotein B-100, vitellogenin-1, vitellogenin-2-like, riboflavin-binding protein, and serotransferrin mainly participated in nutrient (lipid, riboflavin, and iron ion) transport, and vitellogenin-2-like showed a lower abundance after D14. Ovomucoid-like were involved in endopeptidase inhibitory activity and immunoglobulin binding and exhibited a higher expression after D18, suggesting a potential role in promoting the absorption of immunoglobulin and providing passive immune protection for goose embryos after D18. Furthermore, myosin-9 and actin (ACTB) were involved in the tight junction pathway, potentially contributing to barrier integrity. Serum albumin mainly participated in cytolysis and toxic substance binding. Therefore, the high expression of serum albumin, myosin-9, and ACTB throughout the incubation might protect the developing embryo. Apolipoprotein B-100, vitellogenin-1, vitellogenin-2-like, riboflavin-binding protein, and serotransferrin might play a crucial role in providing nutrition for embryonic development, and VTG-2-like was preferentially degraded/absorbed.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

The causal effect of iron status on risk of anxiety disorders: A two-sample Mendelian randomization study.

OBJECTIVES: Observational studies had investigated the association of iron metabolism with anxiety disorders. The conclusions were inconsistent and not available to reveal the causal or reverse-causal association due to the confounding. In this study we estimated the potential causal effect of iron homeostasis markers on anxiety disorders using two-sample Mendelian randomization (MR) analysis. METHODS: Summary data of single nucleotide polymorphisms (SNPs) associated with four iron-related biomarkers were extracted from a recent report about analysis of three genome-wide association study (GWAS), the sample size of which ranged from 131471 to 246139 individuals. The corresponding data for anxiety disorders were from Finngen database (20992 cases and 197800 controls). The analyses were mainly based on inverse variance weighted (IVW) method. In addition, the heterogeneity and pleiotropy of the results were assessed by Cochran's Q test and MR-Egger regression. RESULTS: Basing on IVW method, genetically predicted serum iron level, ferritin and transferrin had negative effects on anxiety disorders. The odd ratios (OR) of anxiety disorders per 1 standard deviation (SD) unit increment in iron status biomarkers were 0.922 (95% confidence interval (CI) 0.862-0.986; p = 0.018) for serum iron level, 0.873 (95% CI 0.790-0.964; p = 0.008) for log-transformed ferritin and 0.917 (95% CI 0.867-0.969; p = 0.002) for transferrin saturation. But no statical significance was found in the association of 1 SD unit increased total iron-binding capacity (TIBC) with anxiety disorders (OR 1.080; 95% CI 0.988-1.180; p = 0.091). The analyses were supported by pleiotropy test which suggested no pleiotropic bias. CONCLUSION: Our results indicated that genetically determined iron status biomarkers causally linked to the risk of anxiety disorders, providing valuable insights into the genetic research and clinical intervention of anxiety disorders.

Nanodrug Hijacking Blood Transferrin for Ferroptosis-Mediated Cancer Treatment.

Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T10 on the surface of cross-linked lipoic acid vesicles (T10@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe2+ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe2+ to further boost the ferroptosis. The results disclosed that T10@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.

Exploring the Specific Role of Iron Center in the Catalytic Activity of Human Serum Transferrin: CTAB-Induced Conformational Changes and Sequestration by Mixed Micelles.

Conformational changes play a seminal role in modulating the activity of proteins. This concept becomes all the more relevant in the context of metalloproteins, owing to the formation of specific conformation(s) induced by internal perturbations (like a change in pH, ligand binding, or receptor binding), which may carry out the binding and release of the metal ion/ions from the metal binding center of the protein. Herein, we investigated the conformational changes of an iron-binding protein, monoferric human serum transferrin (Fe-hTF), using several spectroscopic approaches. We could reversibly tune the cetyltrimethylammonium bromide (CTAB)-induced conformation of the protein, exploiting the concept of mixed micelles formed by three sequestrating agents: (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) hydrate (CHAPS) and two bile salts, namely, sodium cholate (NaC) and sodium deoxycholate (NaDC). The formation of mixed micelles between CTAB and these reagents (CHAPS/NaC/NaDC) results in the sequestration of CTAB molecules from the protein environment and aids the protein in reattaining its native-like structure. However, the guanidinium hydrochloride-induced denatured Fe-hTF did not acquire its native-like structure using these sequestrating agents, which substantiates the exclusive role of mixed micelles in the present study. Apart from this, we found that the conformation of transferrin (adopted in the presence of CTAB) displays pronounced esterase-like activity toward the para-nitrophenyl acetate (PNPA) substrate as compared to native transferrin. We also outlined the impact of the iron center and amino acids surrounding the iron center on the effective catalytic activity in the CTAB medium. We estimated ∼3 times higher specific catalytic efficiency for the iron-depleted Apo-hTF compared to the fully iron-saturated Fe2-hTF in the presence of CTAB.

A redox switch allows binding of Fe(II) and Fe(III) ions in the cyanobacterial iron-binding protein FutA from Prochlorococcus.

The marine cyanobacterium Prochlorococcus is a main contributor to global photosynthesis, whilst being limited by iron availability. Cyanobacterial genomes generally encode two different types of FutA iron-binding proteins: periplasmic FutA2 ABC transporter subunits bind Fe(III), while cytosolic FutA1 binds Fe(II). Owing to their small size and their economized genome Prochlorococcus ecotypes typically possess a single futA gene. How the encoded FutA protein might bind different Fe oxidation states was previously unknown. Here, we use structural biology techniques at room temperature to probe the dynamic behavior of FutA. Neutron diffraction confirmed four negatively charged tyrosinates, that together with a neutral water molecule coordinate iron in trigonal bipyramidal geometry. Positioning of the positively charged Arg103 side chain in the second coordination shell yields an overall charge-neutral Fe(III) binding state in structures determined by neutron diffraction and serial femtosecond crystallography. Conventional rotation X-ray crystallography using a home source revealed X-ray-induced photoreduction of the iron center with observation of the Fe(II) binding state; here, an additional positioning of the Arg203 side chain in the second coordination shell maintained an overall charge neutral Fe(II) binding site. Dose series using serial synchrotron crystallography and an XFEL X-ray pump-probe approach capture the transition between Fe(III) and Fe(II) states, revealing how Arg203 operates as a switch to accommodate the different iron oxidation states. This switching ability of the Prochlorococcus FutA protein may reflect ecological adaptation by genome streamlining and loss of specialized FutA proteins.

Myricetin Oligomer Triggers Multi-Receptor Mediated Penetration and Autophagic Restoration of Blood-Brain Barrier for Ischemic Stroke Treatment.

Restoration of blood-brain barrier (BBB) dysfunction, which drives worse outcomes of ischemic stroke, is a potential target for therapeutic opportunities, whereas a sealed BBB blocks the therapeutics entrance into the brain, making the BBB protection strategy paradoxical. Post ischemic stroke, hypoxia/hypoglycemia provokes the up-regulation of transmembrane glucose transporters and iron transporters due to multiple metabolic disorders, especially in brain endothelial cells. Herein, we develop a myricetin oligomer-derived nanostructure doped with Ce to bypass the BBB which is cointermediated by glucose transporters and iron transporters such as glucose transporters 1 (GLUT1), sodium/glucose cotransporters 1 (SGLT1), and transferrin(Tf) reporter (TfR). Moreover, it exhibits BBB restoration capacity by regulating the expression of tight junctions (TJs) through the activation of protective autophagy. The myricetin oligomers scaffold not only acts as targeting moiety but is the prominent active entity that inherits all diverse pharmacological activities of myricetin. The suppression of oxidative damage, M1 microglia activation, and inflammatory factors makes it a multitasking nanoagent with a single component as the scaffold, targeting domain and curative components.

The association of prealbumin, transferrin, and albumin with immunosenescence among elderly males.

OBJECTIVE: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. METHODS: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. RESULTS: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28- cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28- cells. CONCLUSIONS: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes.

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.

Transferrin maintains the motility rate, ATP content, and DNA integrity of common carp spermatozoa during short-term storage.

Short-term sperm storage is a straightforward and cost-effective method of managing logistics in large scale fish hatchery operations but may result in decline in sperm quality. For effective artificial reproduction of fish, use of an appropriate additive to optimize sperm storage conditions is essential. In this study, it was investigated the effect of purified seminal plasma transferrin (Tf) at 10 µg/ml on relevant parameters in common carp Cyprinus carpio sperm during short-term storage. We compared sperm motility and curvilinear velocity, adenosine triphosphate (ATP) content and DNA fragmentation of fresh spermatozoa to that stored for 24, 48, 72, and 144 h with or without Tf. The percentage of motile cells and the curvilinear velocity of spermatozoa in stored samples for 72 h with transferrin supplementation were greater compared to samples with no added protein. The ATP content in samples without added transferrin was reduced (P < 0.05) after 72 h of storage, in contrast to the levels observed in transferrin-supplemented sperm. A time-dependent increase in DNA fragmentation was observed. Significantly lower DNA damage, expressed as percent tail DNA (10.99 ±â€¯1.28) and olive tail moment (0.54 ±â€¯0.12), was recorded in Tf-supplemented samples stored for 48 h compared to that with no Tf. Hence, it is concluded that the beneficial effects of transferrin on common carp sperm could serve as an additional tool for developing and enhancing short-term sperm preservation procedures commonly used in aquaculture.

Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats.

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.

Cellulose nanocrystals from celery stalk as quercetin scaffolds: A novel perspective of human holo-transferrin adsorption and digestion behaviours.

In this study, cellulose nanocrystals (CNCs) were synthesized from celery stalks to be used as the platform for quercetin delivery. Additionally, CNCs and CNCs-quercetin were characterized using the results of scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and zeta potential, while their interactions with human holo-transferrin (HTF) were also investigated. We examined their interaction under physiological conditions through the exertion of fluorescence, resonance light scattering, synchronized fluorescence spectroscopy, circular dichroism, three-dimensional fluorescence spectroscopy, and fluorescence resonance energy transfer techniques. The data from SEM and TEM exhibited the spherical shape of CNCs and CNCs-quercetin and also, a decrease was detected in the size of quercetin-loaded CNCs from 676 to 473 nm that indicated the intensified water solubility of quercetin. The success of cellulose acid hydrolysis was confirmed based on the XRD results. Apparently, the crystalline index of CNCs-quercetin was reduced by the interaction of CNCs with quercetin, which also resulted in the appearance of functional groups, as shown by FTIR. The interaction of CNCs-quercetin with HTF was also demonstrated by the induced quenching in the intensity of HTF fluorescence emission and Stern-Volmer data represent the occurrence of static quenching. Overall, the effectiveness of CNCs as quercetin vehicles suggests its potential suitability for dietary supplements and pharmaceutical products.

Real-time monitoring of Ti(IV) metal ion binding of transferrin using a solid-state nanopore.

Transferrin, a central player in iron transport, has been recognized not only for its role in binding iron but also for its interaction with other metals, including titanium. This study employs solid-state nanopores to investigate the binding of titanium ions [Ti(IV)] to transferrin in a single-molecule and label-free manner. We demonstrate the novel application of solid-state nanopores for single-molecule discrimination between apo-transferrin (metal-free) and Ti(IV)-transferrin. Despite their similar sizes, Ti(IV)-transferrin exhibits a reduced current drop, attributed to differences in translocation times and filter characteristics. Single-molecule analysis reveals Ti(IV)-transferrin's enhanced stability and faster translocations due to its distinct conformational flexibility compared to apo-transferrin. Furthermore, our study showcases solid-state nanopores as real-time monitors of biochemical reactions, tracking the gradual conversion of apo-transferrin to Ti(IV)-transferrin upon the addition of titanium citrate. This work offers insights into Ti(IV) binding to transferrin, promising applications for single-molecule analysis and expanding our comprehension of metal-protein interactions at the molecular level.

Regulation mechanisms of ferric ions release from iron-loaded transferrin protein caused by nano-sized polystyrene plastics-induced conformational and structural changes.

Currently, the binding of iron-binding protein transferrin (TF) with NPs and their interaction mechanisms have not been completely elucidated yet. Here, we probed the conformation-dependent release of Fe ions from TF induced by nano-sized polystyrene plastics (PS-NPs) using dialysis, ICP-MS, multi-spectroscopic techniques, and computational simulation. The results showed that the release of free Fe ions from TF was activated after PS-NPs binding, which displayed a clear dose-effect correlation. PS-NPs binding can induce the unfolding and loosening of polypeptide chain and backbone of TF. Alongside this we found that the TF secondary structure was destroyed, thereby causing TF protein misfolding and denaturation. In parallel, PS-NPs interacted with the chromophores, resulting in the occurrence of fluorescence sensitization effects and the disruption of the surrounding micro-environment of aromatic amino acids. Also, the binding of PS-NPs induced the formation of new aggregates in the PS-NPs-TF system. Further simulations indicated that PS-NPs exhibited a preference for binding to the hinge region that connects the C-lobe and N-lobe, which is responsible for the Fe ions release and structural alterations of TF. This finding provides a new understanding about the regulation of the release of Fe ions of iron-loaded TF through NPs-induced conformational and structural changes.

Transferrin-inspired iron delivery across the cell membrane using [(L2Fe)2(µ-O)] (L = chlorquinaldol) to harness anticancer activity of ferroptosis.

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.

Single-center experience of congenital disorders of glycosylation syndrome screening in Tunisia: A retrospective study over a 15-year period (2007-2021).

BACKGROUND: We report the results gathered over 15 years of screening for congenital disorders of glycosylation syndrome (CDGS) in Tunisia according to clinical and biochemical characteristics. METHODS: Our laboratory received 1055 analysis requests from various departments and hospitals, for children with a clinical suspicion of CDGS. The screening was carried out through separation of transferrin isoforms by capillary zone electrophoresis. RESULTS: During the 15-year period, 23 patients were diagnosed with CDGS (19 patients with CDG-Ia, three patients with CDG-IIx, and one patient with CDG-X). These patients included 13 boys and 10 girls aged between 3 months and 13 years, comprising 2.18 % of the total 1055 patients screened. The incidence for CDGS was estimated to be 1:23,720 live births (4.21 per 100,000) in Tunisia. The main clinical symptoms related to clinical disease state in newborn and younger patients were psychomotor retardation (91 %), cerebellar atrophy (91 %), ataxia (61 %), strabismus (48 %), dysmorphic symptoms (52 %), retinitis pigmentosa, cataract (35 %), hypotonia (30 %), and other symptoms. CONCLUSION: In Tunisia, CDGS still remains underdiagnosed or misdiagnosed. The resemblance to other diseases, especially neurological disorders, and physicians' unawareness of the existence of these diseases are the main reasons for the underdiagnosis. In routine diagnostics, the screening for CDGS by biochemical tests is mandatory to complete the clinical diagnosis.

Toenail and serum levels as biomarkers of iron status in pre- and postmenopausal women: correlations and stability over eight-year follow-up.

Iron status is often assessed in epidemiologic studies, and toenails offer a convenient alternative to serum because of ease of collection, transport, and storage, and the potential to reflect a longer exposure window. Very few studies have examined the correlation between serum and toenail levels for trace metals. Our aim was to compare iron measures using serum and toenails on both a cross-sectional and longitudinal basis. Using a subset of the US-wide prospective Sister Study cohort, we compared toenail iron measures to serum concentrations for iron, ferritin and percent transferrin saturation. Among 146 women who donated both blood and toenails at baseline, a subsample (59%, n = 86) provided specimens about 8 years later. Cross-sectional analyses included nonparametric Spearman's rank correlations between toenail and serum biomarker levels. We assessed within-woman maintenance of rank across time for the toenail and serum measures and fit mixed effects models to measure change across time in relation to change in menopause status. Spearman correlations at baseline (follow-up) were 0.08 (0.09) for serum iron, 0.08 (0.07) for transferrin saturation, and - 0.09 (- 0.17) for ferritin. The within-woman Spearman correlation for toenail iron between the two time points was higher (0.47, 95% CI 0.30, 0.64) than for serum iron (0.30, 95% CI 0.09, 0.51) and transferrin saturation (0.34, 95% CI 0.15, 0.54), but lower than that for ferritin (0.58, 95% CI 0.43, 0.73). Serum ferritin increased over time while nail iron decreased over time for women who experienced menopause during the 8-years interval. Based on cross-sectional and repeated assessments, our evidence does not support an association between serum biomarkers and toenail iron levels. Toenail iron concentrations did appear to be moderately stable over time but cannot be taken as a proxy for serum iron biomarkers and they may reflect physiologically distinct fates for iron.