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Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28–72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32–74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C‐reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony‐stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1β (IL1β) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron. [ABSTRACT FROM AUTHOR]

The pathogenesis of systemic sclerosis (SSC) fibrosis involves the rapid proliferation of skin fibroblasts, and current anti-fibrotic treatments are limited. This study investigated the relationship between ferroptosis and SSC skin fibroblasts. We observed that erastin-induced ferroptosis was suppressed in SSC fibroblasts. RSL3, a direct inhibitor of Glutathione Peroxidase 4 (GPX4), significantly reduced the viability of the fibroblasts, and upregulation of GPX4 in the SSC fibroblasts contributed to ferroptosis resistance. Furthermore, we demonstrated that transferrin receptor 1 (TfR1) was a crucial transporter for iron deposition in the fibroblasts. Collectively, our results highlight that GPX4 inhibition could enhance the sensitivity to ferroptosis by SSC fibroblasts, which showed distinct characteristics of iron metabolism that were not observed in normal fibroblasts in this study. Taken together, these results suggest that targeting ferroptosis could be a therapeutic strategy for the treatment of SSC. [Display omitted] • Upregulation of GPX4 in SSC skin fibroblasts contributed to Erastin resistance. • TfR1 was a crucial transporter for iron deposition in SSC skin fibroblasts. • Downregulation of Ft-H and Ft-L indicated that cellular iron storage was inhibited in SSC fibroblasts. • NRF2 was decreased in SSC fibroblasts. [ABSTRACT FROM AUTHOR]

We report a successful formulation of Artemisone (ATM) in transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs), achieving nearly a five-times increase in cell toxicity. The escalating cost of new drug discoveries led to the repurposing of approved drugs for new indications. This study incorporated Artemisone, an antimalarial drug, into a nanostructured lipid carrier (NLC) and tested for possible anticancer effects. The aim was to develop NLCs, and transferrin-conjugated NLCs (NLC-Tf) encapsulating Artemisone to enhance its delivery and anticancer activity. NLC formulations were prepared using high-pressure homogenization followed by ultrasonication and were characterized by particle size, zeta potential, and PDI. The conjugation of (Tf) to (NLC) was confirmed using IR, and the anticancer activity was tested using MTS assay. All formulations were in the nanometer size range (140–167 nm) with different zeta potential values. IR spectroscopy confirmed the successful conjugation of transferrin to NLC. Upon testing the formulations on melanoma cell lines using MTS assay, there was a significant decrease in viability and an increase in the encapsulated ATM-Tf toxicity compared to positive control ATM. The NLCs presented a promising potential carrier for delivering ATM to melanoma cells, and further conjugation with Tf significantly improved the ATM cytotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: Physical activity induces numerous modifications in the morphological, rheological, and biochemical properties of blood. The purpose of this study was to evaluate changes in blood rheological and biochemical indicators among runners. Also, we assessed how the rheological and biochemical properties of blood in people who practised running characterised the range and direction of exercise modifications and allowed for the diagnosis of transient adaptive effects. Methods: This study included 12 athletes who regularly trained in middle- and long-distance running (6–8 times a week) and presented a high sports level (national and international class). The athletes performed a 30 min warm-up consisting of 15 min of jogging and exercises. After a 10 min rest, they completed a 3 km run with submaximal effort. Blood samples were collected at baseline and after the effort. Results: No statistically significant changes were revealed in erythrocyte, leukocyte, platelet, iron, ferritin, transferrin, erythropoietin, or C-reactive protein concentrations in the examined runners. The same applied to the elongation index at a shear stress within the range of 0.30–60.00 Pa, amplitude and total extent of aggregation, aggregation half-life, and aggregation index. A significant increase (within standard limits) was only observed in fibrinogen concentration after running. Conclusions: The lack of post-exercise changes in blood rheological and biochemical indicators in the investigated runners points at an efficient haemorheological system. This, in turn, reflects well-executed training and remarkably well-trained adaptive systems responsible for regeneration. [ABSTRACT FROM AUTHOR]

Primary aldosteronism is a common clinical syndrome in hypertensive patients. Early identification and timely treatment of primary aldosteronism are of great significance to improve the prognosis of patients. Endothelial dysfunction is currently considered an important potential pathological change in primary aldosteronism. In this study, we observed that the levels of von Willebrand factor and soluble intercellular adhesion molecule-1 were significantly elevated in primary aldosteronism and were closely associated with pathological progression. Von Willebrand factor and soluble intercellular adhesion molecule-1 are important adhesion factors in blood, and their levels are directly related to blood viscosity. Meanwhile, both markers showed excellent efficacy in diagnosing primary aldosteronism in hypertensive patients. Additionally, an inverse correlation of soluble intercellular adhesion molecule-1 and primary aldosteronism with the nutritional protein levels of primary aldosteronism patients was identified, which also confirms the promising potential of von Willebrand factor and soluble intercellular adhesion molecule-1 for dynamic nutritional status assessment in primary aldosteronism. These findings are of great significance for the future clinical diagnosis and treatment of primary aldosteronism. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect of standardized nutrition nursing combined with low molecular weight heparin calcium in treating patients with hyperlipidemic pancreatitis. A total of 100 patients from Yancheng Third People's Hospital were randomly divided into the control group and treatment group using a random number table. The control group received basic treatment that included fasting, isotonic saline, Ibuprofen, gastrointestinal decompression, Fentanyl, Pantoprazole, octreotide, electrolyte balance maintenance, glucose control, and lipid-lowering drug + routine enteral nutrition nursing. On this basis, the treatment group received low molecular weight heparin calcium injection + standardized enteral nutrition nursing. The total effective rate of the treatment group was higher than that of the control group (94.00% versus 76.00%; P < 0.05). After intervention, compared with the control group, serum levels of prealbumin, albumin, and transferrin were significantly higher (P < 0.05), while serum levels of triglyceride, total cholesterol, and amylase were significantly lower (P < 0.05) in the treatment group. Furthermore, improvements in prothrombin time, thrombin time, fibrinogen level, and activated partial thrombokinase time in the treatment group were more obvious (P < 0.05), while serum levels of C-reactive protein, tumor necrosis factor-α, and interleukin-6 were significantly lower (P < 0.05) than those in the control group. No difference was found in the incidence of adverse reactions between the two groups (P > 0.05). Overall, standardized nutrition nursing combined with low molecular weight heparin calcium can reduce blood lipid levels and inflammatory responses, improve coagulation function, and promote the nutritional status of patients with hyperlipidemic pancreatitis. [ABSTRACT FROM AUTHOR]

This study aimed to examine the impact of accelerated rehabilitation surgical nursing combined with enteral nutrition on the postoperative recovery of patients undergoing total hip arthroplasty. We enrolled 100 patients admitted to Ankang People's Hospital between January 2021 and December 2022. The patients were randomly divided into a control group and a treatment group. Patients in the control group received routine nursing and targeted dietary guidance, while those in the treatment group received accelerated rehabilitation surgical nursing and enteral nutrition. Patients in the treatment group exhibited lower intraoperative blood loss, postoperative time of getting out of bed, postoperative hospital stays, visual analog scale scores, and incidence of complications than those in the control group. Additionally, patients in the treatment group exhibited higher Harris scores, Barthel indexes, and higher prealbumin, hemoglobin, transferrin, albumin, immunoglobulins G, A, and M levels, and nursing satisfaction than those in the control group. Accelerated rehabilitation surgical nursing combined with enteral nutrition for patients undergoing total hip arthroplasty can effectively improve hip function and life ability recovery, shorten the rehabilitation time, lower the complication rate, promote the nutritional status and immune function and improve the nursing satisfaction rate of patients. [ABSTRACT FROM AUTHOR]

Introduction: Iron status (ferritin and transferrin saturation [TSAT]) routinely performed to detect iron deficiency. However, these parameters required complicated procedures, expensive costs and took a long time. The hematological parameters including Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), and red cell distribution width (RDW), hypochromic erythrocyte percentage (%Hypo), microcytic erythrocyte percentage (%Micro), and reticulocyte cellular hemoglobin content (CHr) which integrated in a single analyzer were considered as potential iron status parameters. This study aimed to examined the correlation of hematological parameters (MCV, MCH, MCHC, CHr, %Hypo, and %Micro) with iron status. Methods: Participants were medical students of Universitas Gadjah Mada, Yogyakarta, Indonesia, and were selected consecutively. The MCV, MCH, MCHC, RDW, %Hypo, %Micro, and CHr examinations measured with Advia 2120 automatic hematology analyzer, while the iron status results used a Cobas® chemistry analyzer. Correlation analysis was calculated by Spearman correlation tests. Results: There were 80 participants consisting of 10 men (12.5%) and 70 women (87.5%) with an age range of 18-24 years. The correlation of hematological parameters with the examined iron status was statistically significant (p<0.001). Correlation coefficients of ferritin with MCV, MCH, MCHC, CHr, %Hypo, and %Micro were 0.275, 0.337, 0, 381, -0.573, 0.407, -0.628, and -0.362, while TSAT correlation coefficients were 0.327, 0.403, 0.506, -0.553, 0.426, -0.586, and -0.375, respectively. Conclusion: Conventional erythrocyte indices of MCV, MCH, and MCHC have a lower correlation than RDW and the extended erythrocyte indices (CHr, %Hypo, and %Micro). [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Ultra-instantaneous UHT (UI-UHT, >155°C, <0.1 s) treated milk exhibits higher retention of active protein than regular UHT milk. However, UI-UHT products demonstrate increased susceptibility to destabilization during storage. This study aimed at monitoring the destabilizing process of UI-UHT milk across different storage temperatures and uncovering its potential mechanisms. Compared with regular UHT treatment, ultra-instantaneous treatment markedly accelerated the milk's destabilization process. Aged gel formation occurred after 45 d of storage at 25°C, whereas creaming and sedimentation were observed after 15 d at 37°C. To elucidate the instability mechanism, measurements of plasmin activity, protein hydrolysis levels, and proteomics of the aged gel were conducted. In UI-UHT milk, plasmin activity, and protein hydrolysis levels significantly increased during storage. Excessive protein hydrolysis at 37°C resulted in sedimentation, whereas moderate hydrolysis and an increase in protein particle size at 25°C resulted in aged gel formation. Proteomics analysis results indicated that the aged gel from UI-UHT milk contained intact caseins, major whey proteins, and their derived peptides. Furthermore, specific whey proteins including albumin, lactotransferrin, enterotoxin-binding glycoprotein PP20K, and MFGM proteins were identified in the gel. Additionally, MFGM proteins in UI-UHT milk experienced considerable hydrolysis during storage, contributing to fat instability. This study lays a theoretical foundation for optimizing UI-UHT milk storage conditions to enhance the quality of liquid milk products. [Display omitted] [ABSTRACT FROM AUTHOR]

New strategies for enhancing drug delivery to the blood–brain barrier (BBB) represent a major challenge in treating cerebral diseases. Nanoemulsion-based nanocarriers represent an ideal candidate to improve drug delivery thanks to their versatility in functionalization and cargo protection. In this work, a paclitaxel-loaded nano-emulsion has been firstly functionalized and stabilized with two layers constituted of chitosan and hyaluronic acid, and, secondly, the latter has been conjugated to the CRT peptide. CRT is a bioactive peptide that selectively recognizes bEnd.3 cells, a model of the BBB, thanks to its interactions with transferrin (Tf) and its receptor (TfR). Cytotoxic results showed a 41.5% higher uptake of CRT functionalized nano-emulsion than the negative control, demonstrating the ability of this novel tool to be accumulated in brain endothelium tissue. Based upon these results, our approach can be fully generalizable to the design of multifunctional nanocarriers for delivery of therapeutic agents to the central nervous systems. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to develop a root cause analysis (RCA) model for test overutilization, applying it to transferrin overordering at our institution. Methods A comprehensive review was undertaken to establish a systematic RCA model. Upon implementation, the questionnaire identifying the root causes of transferrin overordering with infographic intervention was distributed to clinicians and nurses. Results The RCA model comprises 5 steps: (1) problem identification, (2) causal factor determination, (3) data collection, (4) significant factor identification, and (5) corrective action development and outcome measurement. The major causes of transferrin overutilization were confusion between transferrin and transferrin saturation, as well as unfamiliarity with the laboratory handbook. An infographic reduced postintervention transferrin ordering among clinicians (84.9%, P <.001) and nurses (46.8%, P <.001). Conclusions This study presents a 5-step RCA model that offers a customized method to identify the causes of test overutilization. Applying this model to transferrin at our institution revealed 22 leading root causes. Laboratories are encouraged to adopt this RCA model as it can contribute to optimized patient care and more efficient resource allocation. [ABSTRACT FROM AUTHOR]

Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption. [ABSTRACT FROM AUTHOR]

Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10−8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing. [ABSTRACT FROM AUTHOR]

Ferritin, transferrin, and transferrin receptors I and II play a vital role in iron metabolism, health, and indication of iron deficiency anaemia in fish. To evaluate the use of high‐iron diets to prevent or reverse channel catfish (Ictalurus punctatus) anaemia of unknown causes, we investigated the expression of these iron‐regulatory genes and proteins in channel catfish fed plant‐based diets. Catfish fingerlings were fed five diets supplemented with 0 (basal), 125, and 250 mg/kg of either inorganic iron or organic iron for 2 weeks. Ferritin, transferrin, and transferrin receptor I and II mRNA and protein expression levels in fish tissues (liver, intestine, trunk kidney, and head kidney) and plasma were determined. Transferrin (iron transporter) and TfR (I and II) genes were generally highly expressed in fish fed the basal diet compared to those fed the iron‐supplemented diets. In contrast, ferritin (iron storage) genes were more expressed in the trunk kidney of fish fed the iron‐supplemented diets than in those fed the basal diet. Our results demonstrate that supplementing channel catfish plant‐based diets with iron from either organic or inorganic iron sources affected the expression of the iron‐regulatory genes and increased body iron status in the fish. [ABSTRACT FROM AUTHOR]

In the small intestine, nutrients from ingested food are absorbed and broken down by enterocytes, which constitute over 95% of the intestinal epithelium. Enterocytes demonstrate diet- and segment-dependent metabolic flexibility, enabling them to take up large amounts of glutamine and glucose to meet their energy needs and transfer these nutrients into the bloodstream. During glycolysis, ATP, lactate, and H+ ions are produced within the enterocytes. Based on extensive but incomplete glutamine oxidation large amounts of alanine or lactate are produced. Lactate, in turn, promotes hypoxia-inducible factor-1α (Hif-1α) activation and Hif-1α-dependent transcription of various proton channels and exchangers, which extrude cytoplasmic H+-ions into the intestinal lumen. In parallel, the vitamin C-dependent and duodenal cytochrome b-mediated conversion of ferric iron into ferrous iron progresses. Finally, the generated electrochemical gradient is utilized by the divalent metal transporter 1 for H+-coupled uptake of non-heme Fe2+-ions. Iron efflux from enterocytes, subsequent binding to the plasma protein transferrin, and systemic distribution supply a wide range of cells with iron, including erythroid precursors essential for erythropoiesis. In this review, we discuss the impact of vitamin C on the redox capacity of human erythrocytes and connect enterocyte function with iron metabolism, highlighting its effects on erythropoiesis. [ABSTRACT FROM AUTHOR]

Parkinson's disease is one of the most prevalent neurological disorders affecting millions of people worldwide. There is a growing demand for novel and natural substances as complementary therapies. Essential oils and their various compounds are highly investigated natural plant-based products as potential treatment options for common human diseases, such as microbial infections, chronic diseases, and neurodegenerative disorders. The present study focuses on the beneficial effects of linalool and geraniol, the major compounds of lavender (Lavandula angustifolia L.) and geranium (Pelargonium graveolens L'Hér. in Aiton) essential oils, on oxidative stress, inflammation, and iron metabolism of the rotenone and 6-hydroxydopamine-induced in vitro Parkinson's models. The experiments were carried out on all-trans retinoic acid differentiated SH-SY5Y cells. The effects of linalool and geraniol were compared to rasagiline, an MAO-B inhibitor. The results revealed that both essential oil compounds reduce the level of reactive oxygen species and alter the antioxidant capacity of the cells. They lower the secretion of IL-6, IL-8, and IL-1β pro-inflammatory cytokines. Moreover, linalool and geraniol change the expression of iron-related genes, such as the iron importer transferrin receptor 1, heme-oxygenase-1, and ferroportin iron exporter, and influence the intracellular iron contents. In addition, it has been unveiled that iron availability is concatenated with the actions of the essential oil compounds. Based on the results, linalool and geraniol are vigorous candidates as an alternative therapy for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association. Methods: We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran's Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings. Results: No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892–0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888–0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy. Conclusion: While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN. [ABSTRACT FROM AUTHOR]

Background: The benefits and risks of bifid triple viable preparations in patients with acute ischemic stroke (AIS) are still controversial. This study aimed to assess the efficacy and safety of bifid triple viable preparations in combination with enteral nutrition for the management of AIS. Methods: Eight public databases including China National Knowledge Infrastructure, China Biology Medicine, VIP, WanFang, EBSCO, PubMed, Cochrane Library, and Web of Science were searched for relevant clinical literature, published through January 2024. These data were then used in the present meta-analysis. Results: A total of 15 studies involving 1,544 patients were included in the metaanalysis. In terms of nutritional status, the results showed that compared with enteral nutrition alone, the bifid triple viable preparation combination group increased the levels of total protein (mean difference [MD], 5.53; 95%confidence interval [CI], 1.94-9.12; p = 0.003), albumin (MD, 4.01; 95%CI, 2.96-5.06; p < 0.00001), prealbumin (MD, 23.08; 95%CI, 16.22-29.95; p < 0.00001), hemoglobin (MD, 9.31; 95%CI, 6.34-12.27; p < 0.00001), and transferrin (MD, 0.64; 95%CI, 0.23-1.05; p = 0.002); in terms of neurological function, it improved the Glasgow Coma Scale (MD, 2.09; 95%CI, 0.69-3.49; p = 0.003), National Institute of Health Stroke Scale (MD, -3.07; 95%CI, -3.73 to -2.40; p < 0.00001), and Neurological Disability Score (MD, -6.68; 95%CI, -7.29 to -6.08; p < 0.00001); in terms of intestinal barrier function, it reduced the levels of endotoxin (MD, -0.55; 95%CI, -0.71 to -0.39; p < 0.00001), D-lactic acid (MD, -3.17; 95%CI, -4.07 to -2.26; p < 0.00001), diamine oxidase (MD, -4.39; 95%CI, -6.20 to -2.57; p < 0.00001), and endothelin (MD, -21.35; 95%CI, -27.86 to -14.83; p < 0.00001); in terms of immune function, it increased the levels of immunoglobulin G (MD, 1.01; 95%CI, 0.20-1.82; p = 0.01) and immunoglobulin M (MD, 0.16; 95%CI, 0.02-0.30; p = 0.03). Additionally, it reduced the incidence of pulmonary infection, vomiting, constipation, and diarrhea, while there were no significant differences in total adverse events, abdominal distension, anorexia, reflux, gastrointestinal bleeding, or electrolyte disturbance. Conclusion: The addition of bifid triple viable preparation to enteral nutrition improved the nutritional status, neurological function, intestinal barrier function, and immune function of patients with AIS, and reduced the risk of infection and gastrointestinal events. [ABSTRACT FROM AUTHOR]

Background: This study sought to investigate the correlation between serum sex hormone-binding globulin (SHBG) levels and nutrition indicators and the malnutrition exposure risk in men and postmenopausal women with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional analysis was conducted, involving patients diagnosed with T2DM at the Guangdong Provincial People's Hospital between May 2018 and December 2019. Results: The study comprised 551 participants (363 men, mean age of 55.55 ± 11.57 years), among whom 167 (30.31%) were classified as with malnutrition exposure risk (GNRI ≤ 98). Multivariable logistic regression analysis revealed that SHBG (OR = 1.04, 95% CI: 1.02–1.05, P < 0.001), glycated hemoglobin (OR = 1.36, 95% CI: 1.22–1.51, P < 0.001), hemoglobin (OR = 0.96, 95% CI: 0.94–0.97, P < 0.001), and non-alcoholic fatty liver disease (OR = 0.41, 95% CI: 0.23–0.73, P < 0.003) were independently associated with the malnutrition exposure risk. SHBG was inversely correlated with body mass index (males: r = -0.34; postmenopausal females: r = -0.22), albumin (males: r = -0.30; postmenopausal females: r = -0.20), transferrin (males: r = -0.28; postmenopausal females: r = -0.19), and prealbumin (males: r = -0.35; postmenopausal females: r = -0.30) (all P < 0.05). Conclusions: Serum SHBG levels are correlated with nutritional indicators and the risk of malnutrition in men and postmenopausal women with T2DM. A multicenter prospective study is imperative to verify this result in the future. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism. [ABSTRACT FROM AUTHOR]

A serum ferritin level <15 to 20 μg/L historically identified patients who had absent bone marrow iron stores, but serum ferritin levels are distorted by the systemic inflammatory states seen in patients with chronic kidney disease or heart failure. As a result, nearly 25 years ago, the diagnostic ferritin threshold was increased 5- to 20-fold in patients with chronic kidney disease (ie, iron deficiency was identified if the serum ferritin level was <100 μg/L, regardless of transferrin saturation [TSAT], or 100 to 299 μg/L if TSAT was <20%). This guidance was motivated not by the findings of studies of total body or tissue iron depletion, but by a desire to encourage the use of iron supplements to potentiate the response to erythropoiesis-stimulating agents in patients with renal anemia. However, in patients with heart failure, this definition does not reliably identify patients with an absolute or functional iron-deficiency state, and it includes individuals with TSATs (≥20%) and serum ferritin levels in the normal range (20–100 mg/L) who are not iron deficient, have an excellent prognosis, and do not respond favorably to iron therapy. Furthermore, serum ferritin levels may be distorted by the use of both neprilysin and sodium-glucose cotransporter 2 inhibitors, both of which may act to mobilize endogenous iron stores. The most evidence-based and trial-tested definition of iron deficiency is the presence of hypoferremia, as reflected by as a TSAT <20%. These hypoferremic patients are generally iron deficient on bone marrow examination, and after intravenous iron therapy, they exhibit an improvement in exercise tolerance and functional capacity (when meaningfully impaired) and show the most marked reduction (ie, 20%–30%) in the risk of cardiovascular death or total heart failure hospitalizations. Therefore, we propose that the current ferritin-driven definition of iron deficiency in heart failure should be abandoned and that a definition based on hypoferremia (TSAT <20%) should be adopted. [ABSTRACT FROM AUTHOR]

Objective: To investigate the distribution of nine (9) urine biomarkers in people living with type 2 diabetes mellitus (T2DM), with or without microvascular complications. Methods: In total, 407 people with T2DM were enrolled from 2021 to 2022. According to diabetic retinopathy (DR) and urinary albumin-creatinine ratio (UACR), the 407 people were divided into four (4) groups, DR(–)UACR(–), DR(+)UACR(–), DR(–)UACR(+), and DR(+)UACR(+). In addition, 112 healthy volunteers were enrolled during the same period. The nine (9) urine markers included α1-microglobulin (u-α1MG), immunoglobulin G (u-IgG), neutrophil gelatinase-associated lipid carrier protein (u-NGAL), cystatin C (u-CysC), retinol-binding protein (u-RBP), β2-microglobulin (u-β2MG), N-acetyl-β-D-glucosaminidase (u-NAG), transferrin (u-Trf), and collagen type IV (u-Col). For each marker, the respective level of 97.5 percentile in healthy volunteers was taken as an upper reference limit. Results: Among the 407 people, 248 individuals (61%) were DR(–)UACR(–), 100 (25%) were DR(-)UACR(+), 37 (9%) were DR(+)UACR(–), and 22 (5%) were DR(+)UACR(+). The u-NAG/Cr biomarker level showed a significant difference between healthy participants and people with T2DM. In the DR(–)UACR(–)group, u-Trf/Cr showed the highest positive rate (21.37%), followed by u-IgG/Cr (14.52%); u-NAG/Cr (10.48%); u-β2MG/Cr (4.44%); u-CysC/Cr (4.03%); u-NGAL/Cr (4.03%); u-RBP/Cr (2.82%); u-α1MG/Cr (2.42%); 17.34% of people with T2DM showed multiple biomarkers positive (≥2 biomarkers). The positive rates of one biomarker (21.33%) and two biomarkers (18.67%) in people who have less than five (5) years of T2DM were almost close to those of the DR(–)UACR(–) group (21.37%, and 12.10%, respectively). Conclusion: Renal tubule biomarkers may be used as an indicator in the early detection and monitoring of renal injury in diabetes mellitus. The u-NAG biomarker should be measured for the people with T2DM of the first-time diagnosis. [ABSTRACT FROM AUTHOR]

Background: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15–21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. Results: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. Conclusions: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars. [ABSTRACT FROM AUTHOR]

Physiological or pathophysiological changes lead to posttranslational changes in the sialic acid content of human serum transferrin (hTf), an essential mediator of iron transport in the human body, resulting in a significantly increased concentration of desialylated hTf. The intrinsic fluorescence quenching upon binding of iron to hTf was successfully modeled using the binding polynomial for two iron-binding sites, allowing measurements in a high-throughput format. Removal of sialic acid residues resulted in a 3-fold increase in iron binding affinity for both sites of hTf at pH 7.4. The pH-dependence of iron binding showed significant differences in equilibrium constants, resulting in a 10-fold increase in binding affinity for desialylated hTf at pH 5.9. The changes in hTf sialylation apparently result in tuning of the stability of the conformational state, which in turn contributes to the stability of the diferric hTf. The observed differences in the conditional thermodynamic equilibrium constants suggest that the desialylated protein has a higher preference for diferric hTf over monoferric hTf species down to pH 6.5, which may also influence the interaction with transferrin receptors that preferentially bind to diferric hTf. The results suggest a link between changes in hTf glycan structure and alterations in iron binding equilibrium associated with tissue acidosis. [ABSTRACT FROM AUTHOR]

Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking.We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay.Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation.Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long‐term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin‐hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors. [ABSTRACT FROM AUTHOR]

The available evidence suggests that the kidney may contribute importantly to the development of an iron deficiency state in patients with heart failure and may be injured by therapeutic efforts to achieve iron repletion. The exceptional workload of the proximal renal tubule requires substantial quantities of iron for ATP synthesis, which it derives from Fe3+ bound to transferrin in the bloodstream. Following ferrireduction, Fe2+ is conveyed by divalent transporters (e.g. DMT1) out of the endosome of the proximal renal tubule, and highly reactive Fe2+ can be directed to the mitochondria, sequestered safely in a ferritin nanocage or exported through the actions of hepcidin‐inhibitable ferroportin. The actions of ferroportin, together with transferrin endocytosis and DMT1‐mediated transport, play a key role in the recycling of iron from the tubular fluid into the bloodstream and preventing the loss of filtered iron in the urine. Activation of endogenous neurohormonal systems and proinflammatory signalling in heart failure decrease megalin‐mediated uptake and DMT1 expression, and increase hepcidin‐mediated suppression of ferroportin, promoting the loss of iron in the urine and contributing to the development of an iron deficiency state. Furthermore, the failure of ferroportin‐mediated efflux at the basolateral membrane heightens the susceptibility of the renal tubules to cytosolic excesses of Fe2+, causing lipid peroxidation and synchronized cell death (ferroptosis) through the iron‐dependent free radical theft of electrons from lipids in the cell membrane. Ferroptosis is a central mechanism to most disorders that can cause acute and chronic kidney disease. Short‐term bolus administration of intravenous iron can cause oxidative stress and is accompanied by markers of renal injury. Experimentally, long‐term maintenance of an iron‐replete state is accompanied by accelerated loss of nephrons, oxidative stress, inflammation and fibrosis. Intravenous iron therapy increases glomerular filtration rate rapidly in patients with heart failure (perhaps because of a haemodynamic effect) but not in patients with chronic kidney disease, and the effects of intravenous iron on the progression of renal dysfunction in the long‐term trials — AFFIRM‐AHF, IRONMAN and HEART‐FID — have not yet been reported. Given the potential role of dysregulated renal iron homeostasis in the pathogenesis of iron deficiency and the known vulnerability of the kidney to intravenous iron, the appropriate level of iron repletion with respect to the risk of acute and chronic kidney injury in patients with heart failure requires further study. [ABSTRACT FROM AUTHOR]

Ferroptosis has been implicated in several neurological disorders and may be therapeutically targeted. However, the susceptibility to ferroptosis varies in different cells, and inconsistent results have been reported even using the same cell line. Understanding the effects of key variables of in vitro studies on ferroptosis susceptibility is of critical importance to facilitate drug discoveries targeting ferroptosis. Here, we showed that increased cell seeding density leads to enhanced resistance to ferroptosis by reducing intracellular iron levels. We further identified iron‐responsive protein 1 (IRP1) as the key protein affected by cell density, which affects the expression of ferroportin or transferrin receptor and results in altered iron levels. Such observations were consistent across different cell lines, indicating that cell density should be tightly controlled in studies of ferroptosis. Since cell densities vary in different brain regions, these results may also shed light on selective regional vulnerability observed in neurological disorders. [ABSTRACT FROM AUTHOR]

This study aimed to ascertain the effects of health education combined with nutrition support nursing on the nutritional status and quality of life of patients with pulmonary tuberculosis. A clinical study was conducted. Sixty-four patients with tuberculosis were selected as the study participants and divided into control and observation groups (n = 32). Both groups received antituberculosis drugs. The control group received standard nursing care, while the observation group received health education in conjunction with nutrition support nursing. After 3 months of intervention, the total effective treatment rate and adherence were compared. Before and after the intervention, the albumin (ALB), prealbumin (PA), transferrin (TF), and hemoglobin (Hb) level, body mass index (BMI), and Short Form-36 (SF-36) scores were compared. The occurrence of adverse reactions during intervention was recorded. Following the intervention, the observation group exhibited a higher treatment total effective rate and increased levels of ALB, PA, TF, Hb, and BMI compared with the control group (p < 0.05). The observation group demonstrated a higher total adherence rate and a lower incidence of adverse reactions compared with the control group (p < 0.05); the SF-36 score of the observation group was higher than that of the control group (p < 0.05). The integration of health education and nutrition support nursing can effectively enhance the therapeutic outcomes of patients with pulmonary tuberculosis. This approach not only improves their nutritional status, treatment adherence, and quality of life, but also reduces the incidence of adverse reactions. The findings of this study lay a solid foundation for further exploration of the combined effects of health education and nutrition support nursing on pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and Frontotemporal lobar degeneration (FTLD) represent the most common forms of neurodegenerative dementias with a highly phenotypic variability. Herein, we investigated the role of genetic variants related to the immune system and inflammation as genetic modulators in AD and related dementias. In patients with sporadic AD/FTLD (n = 300) and GRN/C9orf72 mutation carriers (n = 80), we performed a targeted sequencing of 50 genes belonging to the immune system and inflammation, selected based on their high expression in brain regions and low tolerance to genetic variation. The linear regression analyses revealed two genetic variants: (i) the rs1049296 in the transferrin (TF) gene, shown to be significantly associated with age at onset in the sporadic AD group, anticipating the disease onset of 4 years for each SNP allele with respect to the wild-type allele, and (ii) the rs7550295 in the calsyntenin-1 (CLSTN1) gene, which was significantly associated with age at onset in the C9orf72 group, delaying the disease onset of 17 years in patients carrying the SNP allele. In conclusion, our data support the role of genetic variants in iron metabolism (TF) and in the modulation of the calcium signalling/axonal anterograde transport of vesicles (CLSTN1) as genetic modulators in AD and FTLD due to C9orf72 expansions. [ABSTRACT FROM AUTHOR]

Objective To assess the diagnostic value of urinary transferrin (Tf) in early diabetic nephropathy (DN) to propose a more sensitive and noninvasive biomarker for screening and monitoring DN in clinical practice. Methods We searched 3 databases from their inception to May 2023, to identify studies investigating the diagnostic value of Tf in patients with DN. Meta-DiSc software, version 1.4, and Stata software, version 15.1 (StataCorp) were used to conduct a meta-analysis and evaluate the diagnostic accuracy of urine Tf levels for DN. Results The meta-analysis included 6 relevant studies investigating the diagnostic value of Tf level for DN. Urinary Tf as a diagnostic marker demonstrated a combined sensitivity of 0.82 (95% CI, 0.71-0.89) and specificity of 0.88 (0.84-0.92). the positive diagnostic likelihood ratio was 7.07 (4.57-10.93), the negative diagnostic likelihood ratio was 0.20 (0.12-0.35), and the diagnostic odds ratio was 34.49 (13.61-87.44). Also, the area under the receiver operating characteristic curve was 0.92 (0.89-0.94), indicating that urinary Tf has a decent discriminative ability in diagnosing DN. Conclusion Tf level is a valuable biological marker for early diagnosis and monitoring of DN in clinical practice. It has statistically significant predictive value for patients in the early phases of DN. [ABSTRACT FROM AUTHOR]

Patients with neurocritically illness are an under-recognized population at high risk of sepsis. We aimed to investigate the prevalence, early predictors, and outcomes of sepsis in neuro-ICU. Daily and accumulative incidences of sepsis in neuro-ICU were explored. Demographics, medical history, baseline disease severity scores, and baseline biomarkers regarding inflammation, immunology, organ function, and nutritional status were collected and analyzed as potential predictors of sepsis. Logistic regression analyses were used to determine the independent predictors, and a nomogram was used to estimate the individual probability of sepsis in neuro-ICU. 153 patients were included in this study. Fifty-nine (38.6%) patients developed sepsis, and 21 (14%) patients developed septic shock. More than 86% of the septic cases occurred within the first week. Sequential organ failure assessment score ((relative risk) RR 1.334, P =.026), history of diabetes (RR 2.346, P =.049), and transferrin (RR 0.128, P =.042) on admission are independent predictors of sepsis. Septic patients had significantly higher mortality (P =.011), higher medical cost (P =.028), and a lower rate of functional independence (P =.010), compared to patients without sepsis. Sepsis afflicted more than one-third of neurocritically-ill patients and occurred mostly in the first week of admission. History of diabetes, serum transferrin, and sequential organ failure assessment score on admission were early predictors. Sepsis led to significantly worse outcomes and higher medical costs. [Display omitted] • Sepsis is common in neuro-ICU and occurs mostly in the first week of admission. • Sepsis leads to significantly worse outcomes and higher medical costs. • History of diabetes, transferrin, and SOFA score on admission are early predictors. [ABSTRACT FROM AUTHOR]

Background: The prevalence of pulmonary hypertension (PH) is reported between 17% and 56% in hemodialysis patients. The pathogenesis of PH in hemodialysis patients is still unclear. Malnutrition may be associated with impaired pulmonary function in hemodialysis patients. Objectives: The present study aimed to investigate the association between PH and nutritional and biochemical markers in hemodialysis patients. Methods: In this cross-sectional study, 80 patients undergoing hemodialysis at the Kowsar Medical Center, Semnan, Iran, from 1 March 2016 to 31 August 2016 were enrolled by complete enumeration. Pulmonary artery pressure was determined by echocardiography between hemodialysis sessions. Arm circumference, triceps fat mass, and body mass index (BMI) were determined. Other laboratory tests included transferrin, serum albumin, cholesterol, triglyceride, and hemoglobin. The source of receiving protein was recorded in a questionnaire. The data were analyzed by the chi-square test and logistic regression analysis at a significance level of less than 0.05. Results: Pulmonary hypertension ( > 25 mmHg) was found in 32 (40%) of the 80 patients studied. The mean of pulmonary pressure in patients with PH was 34.66 ± 5.6 mmHg compared to 16.85 ± 3.7 mmHg in patients without PH. Age, gender, arm circumference, frequency of dialysis per year, and serum levels of albumin, transferrin, triglyceride, and total cholesterol were not significantly different between patients with and without PH. There was a significant difference in the mean hemoglobin level between patients with and without PH (P = 0.003). The likelihood of developing PH was reduced by 0.3 in those with hemoglobin ≥ 11 g/dL compared to patients with hemoglobin levels below 11 g/dL (OR = 0.400, P = 0.003). The likelihood of developing PH in patients with albumin ≥ 3.8 g/L decreased by 0.126 compared to those with albumin less than 3.8 (OR = 0.126, P = 0.003). Conclusions: The results of our study indicated a higher incidence of PH in patients with lower levels of hemoglobin and albumin. So, patients undergoing hemodialysis are recommended to be regularly screened for these two variables. [ABSTRACT FROM AUTHOR]

Purpose of Review: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies. Recent Findings: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle–Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). Summary: The most important proteins identified involved transferrin, α-, β-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response. [ABSTRACT FROM AUTHOR]

Transferrin, Tf, the protein that transports iron as Fe(III) from the blood to the tissues via endocytosis, is believed to also transport Cr(III). Under physiological conditions, Tf binds and releases Cr(III) rapidly from Cr(III)2-Tf; however, the major form of Tf in the bloodstream is mono-ferric Tf (Fe(III)-Tf). Given the low concentration of Cr(III) in the bloodstream, the form of Cr(III)-containing Tf that is transported is probably monochromic, monoferric-Tf (Cr(III),Fe(III)-Tf). Given that Tf has two specific metal-binding sites, one in both its C-terminal and its N-terminal lobe, two forms of Cr(III),Fe(III)-Tf can form. The binding of Cr(III) to mono-ferric Tf to generate both forms of Cr(III),Fe(III)-Tf has been examined in detail for the first time. The addition of Cr(III) to monoferric Tfs in 100 mM HEPES and 25 mM bicarbonate solution, pH 7.4, resulted in a rapid binding of Cr(III) to the open metal-binding site of the Tfs. Titrations of the monoferric Tfs with Cr(III) indicate the tight binding on one Cr(III) in each case. The binding of Cr(III) to monoferric Tfs is accompanied by conformational changes similar to adding two equivalents of Cr(III) to apoTf. Thus, mono-ferric Tfs bind one equivalent of Cr(III) rapidly and tightly to form mixed Cr(III),Fe(III)-Tfs. Cr(III) is probably transported as mixed Cr(III),Fe(III)-Tfs. [ABSTRACT FROM AUTHOR]

Background: Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably. Aim: To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland. Design & setting: We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System. Method: The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined. Results: The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P<0.001). Anaemia increased with advancing age (33.4% for those aged >75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60–89, 30–59 and <30 ml/min/1.73 m², respectively, P<0.001). After 3-months' follow-up, the proportion screened for iron deficiency was 11.2% based on transferrin saturation and 33.7% using serum ferritin. Screening for folate and B12 deficiency was 17.6% and 19.8%, respectively. Among screened patients, the prevalence of iron deficiency, B12, and folate deficiency was 37.0%, 6.3%, and 5.8%, respectively. Conclusion: The burden of anaemia in the healthcare system is substantial especially for older patients and those with advanced kidney disease. Low screening rates for iron, B12, and folate deficiency are common and warrant quality improvement initiatives. [ABSTRACT FROM AUTHOR]

With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients. [ABSTRACT FROM AUTHOR]

Micronutrient deficiencies, including iron deficiency, are linked to different cognitive impairments and sensory functions. However, whether circulating iron levels affect self-assessed multiple intelligence (MI) scores in adolescents remains uninvestigated. This study aimed to investigate associations between serum iron levels and self-assessed MI scores in adolescents in Riyadh, Saudi Arabia. Recruiting 434 Saudi adolescents (174 boys and 260 girls, aged 12–17), we administered the McKenzie questionnaire to assess MI across nine categories. Anthropometrics and fasting blood samples were collected to measure circulating iron and transferrin levels. Total iron-binding capacity (TIBC) and transferrin saturation (TSAT) levels were calculated. Notably, girls exhibited significantly higher MI scores in the interactive domain than boys (age and BMI-adjusted OR = 1.36, 95% confidence interval = 1.07–1.73, p = 0.01). No significant correlations were observed between serum iron and MI. However, normal TSAT levels (TSAT > 20%) corresponded with higher age and BMI-adjusted odds of MI scores in the musical (OR = 1.59, 95%CI = 1.1–2.2, p = 0.006), linguistic (1.57, 1.1–2.3, p = 0.016), kinesthetic (1.48, 1.1–2.1, p = 0.024), spatial (1.45, 1.1–2.1, p = 0.03), and existential (1.56, 1.1–2.1, p = 0.01) categories compared to ones with lower TSAT levels (TSAT ≤ 20%), only in boys. In conclusion, serum iron levels may not directly influence MI domains in adolescents in Riyadh, Saudi Arabia; however, lower TSAT levels, indicative of iron-deficiency anemia, may influence MI, only in boys, indicating a possible relationship between iron metabolism and cognitive functions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the causal relationship between different serum iron statuses (ferritin, transferrin, transferrin saturation, and serum iron) and the occurrence of estrogen receptor (ER)-positive or ER-negative breast cancer. Methods: The summary data on serum iron status exposure were gathered from the IEU OpenGWAS Project, the UK Biobank, and other databases. Concurrently, the summary data for ER+ and ER- breast cancer are sourced from the Breast Cancer Association Consortium (BCAC). By examining the causal link between iron status and breast cancer, we deployed five distinct Mendelian randomization (MR) algorithms, namely MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and MR-PRESSO. To assess heterogeneity and horizontal pleiotropy, Cochran’s Q and MR-Egger algorithms were applied, respectively. Results: Elevated ferritin levels are associated with an increased risk of ER-negative breast cancer (OR(IVW) = 1.042, 95% CI (1.005, 1.081), p = 0.025; OR (weighted median) = 1.050, 95% CI (1.001, 1.102), p = 0.046; and OR (MR-PRESSO) = 1.042, 95% CI (1.005, 1.081), p = 0.039). Conversely, an increase in the serum iron level is linked to a reduced risk of ER-negative breast cancer (OR (IVW) = 0.791, 95% CI (0.649, 0.962), p = 0.019; and OR (MR-PRESSO) = 0.791, 95% CI (0.649, 0.962), p = 0.028). However, there is no evidence of a causal relationship between transferrin, transferrin saturation, and ER-negative breast cancer. For ER-positive breast cancer, none of the four different iron statuses demonstrated a causal relationship. Conclusions: Ferritin is positively correlated with ER-negative breast cancer, while serum iron is negatively associated with ER-negative breast cancer. However, there is no causal relationship between the four iron statuses and ER-positive breast cancer. [ABSTRACT FROM AUTHOR]

It is assumed that bilirubin is hormonally regulated and influences weight development by preventing weight gain. However, studies in healthy infants are limited. The present study established reference values for bilirubin and investigated whether bilirubin levels are significantly associated with body weight, levels of ferritin and transferrin as well as steroid hormone levels in a study population of three- and six-month-old healthy infants. Data from a total of 411 study visits from the LIFE Child study (Leipzig, Germany) were analyzed. Associations were examined using linear regression analyses. Besides laboratory parameters, anthropometric data were gathered. We found statistically significant associations between body weight and bilirubin levels. In girls, we observed additional associations between bilirubin levels and both ferritin and transferrin concentrations at three months of age. At six months, steroid hormone levels were significantly associated with concentrations of total and indirect bilirubin, with effects differing by sex. Our study thus confirms associations already reported from animal studies and studies in adult populations. Furthermore, we showed that these associations already exist in the first year of life, are influenced by sex and age and, further, depend on the bilirubin type. Our results provide reference values for bilirubin and assist, therefore, in interpreting bilirubin levels in infancy. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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]

Abstract Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe2+, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.

Introduction: Iron acts as a cofactor in Thyroid Peroxidase (TPO) activity, and low iron levels can impact thyroid hormone metabolism. The function of ferritin and iron has been extensively documented in various studies in patients with Overt Hypothyroidism (OH), but their role in Subclinical Hypothyroidism (SH) remains largely unexplored. Aim: To evaluate the serum ferritin and iron levels in patients who have SH. Materials and Methods: A retrospective observational study was conducted between March 2018 and October 2018 at the Biochemistry Department of Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India. For the study, a total of 100 cases of SH were enrolled, and these patients were matched in terms of age and sex with 50 healthy controls. A fasting sample was obtained and analysed for serum ferritin, Total Iron Binding Capacity (TIBC), TT3, TT4, and Thyroid Stimulating Hormone (TSH). MedCalc software was used to perform statistical analysis. Results: In the SH group, there were 32 males (32%) and 68 females (68%); in the control group, there were 21 males (42%) and 29 females (58%). The median values of TT3 (nmol/L), TT4 (μg/dL), and TSH (μIU/mL) were 1.55 (1.4-1.95), 7.8 (5.9-9.75), and 3 (1.9-3.75) for controls, and 1.4 (1.1-1.75), 6.85 (5.5-8.15), and 6.2 (4.8-8.05), respectively, for cases. In comparison to controls, the TSH level was significantly higher (p

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the “self-guidance system”, Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Abstract ALG1‐CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N‐acetylglucosamine (GlcNAc2)‐pyrophosphate (PP)‐dolichol to the growing oligosaccharide chain, resulting in impaired N‐glycosylation of proteins. N‐glycosylation has a key role in functionality, stability, and half‐life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3‐year‐old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1‐CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysis of highly glycosylated proteins in fibroblasts revealed decreased intercellular adhesion molecule 1 (ICAM1), but normal lysosomal associated membrane protein 1 and 2 (LAMP1 and LAMP2) expression levels. Glycoproteomics in fibroblasts showed the presence of the abnormal tetrasacharide. Reviewing the literature, we found 86 reported ALG1‐CDG patients, but only one with normal transferrin analysis. Based on our results we would like to highlight the importance of multiple approaches in diagnosing ALG1‐CDG, as normal serum transferrin glycosylation or other biomarkers with normal expression levels can occur.

The bloodstream form of Trypanosoma brucei expresses large poly-N-acetyllactosamine (pNAL) chains on complex N-glycans of a subset of glycoproteins. It has been hypothesised that pNAL may be required for receptor-mediated endocytosis. African trypanosomes contain a unique family of glycosyltransferases, the GT67 family. Two of these, TbGT10 and TbGT8, have been shown to be involved in pNAL biosynthesis in bloodstream form Trypanosoma brucei, raising the possibility that deleting both enzymes simultaneously might abolish pNAL biosynthesis and provide clues to pNAL function and/or essentiality. In this paper, we describe the creation of a TbGT10 null mutant containing a single TbGT8 allele that can be excised upon the addition of rapamycin and, from that, a TbGT10 and TbGT8 double null mutant. These mutants were analysed by lectin blotting, glycopeptide methylation linkage analysis and flow cytometry. The data show that the mutants are defective, but not abrogated, in pNAL synthesis, suggesting that other GT67 family members can compensate to some degree for loss of TbGT10 and TbGT8. Despite there being residual pNAL synthesis in these mutants, certain glycoproteins appear to be particularly affected. These include the lysosomal CBP1B serine carboxypeptidase, cell surface ESAG2 and the ESAG6 subunit of the essential parasite transferrin receptor (TfR). The pNAL deficient TfR in the mutants continued to function normally with respect to protein stability, transferrin binding, receptor mediated endocytosis of transferrin and subcellular localisation. Further the pNAL deficient mutants were as viable as wild type parasites in vitro and in in vivo mouse infection experiments. Although we were able to reproduce the inhibition of transferrin uptake with high concentrations of pNAL structural analogues (N-acetylchito-oligosaccharides), this effect disappeared at lower concentrations that still inhibited tomato lectin uptake, i.e., at concentrations able to outcompete lectin-pNAL binding. Based on these findings, we recommend revision of the pNAL-dependent receptor mediated endocytosis hypothesis. Author summary: Blood-stage trypanosome parasites have a specialised invagination on the cell surface named the flagellar pocket (FP), where invariant essential nutrient receptors are located. The pocket houses diverse proteins, including a transferrin receptor (TfR), which facilitates uptake of host transferrin-bound iron for survival. Several FP proteins, including TfR, are linked to complex sugar molecules (carbohydrates), the functions of which are not well understood. Complex carbohydrates are made by enzymes called glycosyltransferases (GTs) and previously we partially inhibited complex carbohydrate synthesis by deletion of either TbGT8 or TbGT10. However, mutant parasites lacking either one of these enzymes survived, suggesting functional redundancy. Here, we created a parasite mutant that lacks both TbGT8 and TbG10 to understand the combined effect of losing both enzymes. The mutant parasites showed a decreased ability to uptake tomato lectin, a protein that specifically binds to these sugar conjugates in the FP, indicating a reduction in carbohydrate complexity. Despite reduced complexity in the sugar structures attached to TfR, its critical function in transferrin/iron uptake remained effective. Furthermore, the mutants remained viable in culture and in animal models, challenging previous assumptions about the necessity and function of these carbohydrate conjugates. Our findings imply a greater flexibility and redundancy in the carbohydrate complex roles than previously appreciated. [ABSTRACT FROM AUTHOR]

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2–MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA–Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2–MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL−1 to 1 mg mL−1 (R2 = 0.9974), and the LOD was 0.00407 ng mL−1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications. [ABSTRACT FROM AUTHOR]

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer's disease are approved, dozens are in the testing phase, and one was withdrawn, and the other halted, likely due to efficacy issues. However, these outcomes should have been evident since these antibodies cannot enter the brain sufficiently due to the blood–brain barrier (BBB) protectant. However, all products can be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model can be tested quickly and at a low cost and should be applied to bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, and gantenerumab, and their fragments. This paper demonstrates that conjugating with transferrin does not alter the binding to brain proteins such as amyloid-β (Aβ) and α-synuclein. We also present a selection of conjugate designs that will allow cleavage upon entering the brain to prevent their exocytosis while keeping the fragments connected to enable optimal binding to proteins. The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively. [ABSTRACT FROM AUTHOR]