Transferrin Research Articles

Nutritional status affects immune function and exacerbates the severity of pulmonary tuberculosis.

To comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB). This descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4+ count <500 cells/µl or a CD4+/CD8+ ratio <1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results. Compared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668-0.734). The findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB.

The Genetic Diagnostics of Hemochromatosis: Disparities in Low- Versus High-Income Countries.

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management.

Unveiling New Genetic Variants Associated with Age at Onset in Alzheimer's Disease and Frontotemporal Lobar Degeneration Due to C9orf72 Repeat Expansions.

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.

Prevalence of C282Y, H63D and S65C gene mutations in patients with hyperferritinemia undergoing therapeutic phlebotomy suspected of having hereditary hemochromatosis

Background: Hemochromatosis is an autosomal recessive disorder caused by excessive iron overload in parenchymal organs. In Brazil, the prevalence of hereditary hemochromatosis (HH) may vary compared to other countries due to different ethnical backgrounds according to the geographic region studied. The prevalence of C282Y mutation of the HFE gene ranges from three to eight times lower in Brazilians than in Caucasians of Northern European origin. Methods: A retrospective cross-sectional study was carried out in 222 patients submitted to therapeutic phlebotomy between March 2011 and July 2014 in a tertiary hospital blood center. The prevalence of HH was determined in 89 (47.3%) out of 188 (84.6%) patients presenting hyperferritinemia, and divided in two genotype groups: C282Y mutation and other mutations. The HH patients’ geographical and clinical characteristics, serum ferritin rate (SF) and transferrin saturation (TS) were analyzed. Results: The HH group consisted of 71 males (79.7%) and 18 (20.3%) females, with a median age of 51.5 ± 10.6 years. There were 36 (40.0%) symptomatic patients and 65 (73.0%) tested positive for the HFE mutation. The initial baseline TS values were significantly higher in primary HH patients (48.6%, IC 95% 43.2% - 55.7%) compared to those with secondary HH (35.0%, IC 95% 27.5% 41.8%, p=0.001). Conclusion: The prevalence of C282Y mutation was higher in this population from the South region compared to previous reports in the Brazilian population, yet inferior to that of Northern Europeans.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars

BackgroundBoars 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.Results1) 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.ConclusionsDietary 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.

Hepatic Oxidative Stress and Cell Death Influenced by Dietary Lipid Levels in a Fresh Teleost.

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation, affecting physiological and pathological processes. Fatty liver disease associated with metabolic dysfunction is a common pathological condition in aquaculture. However, the exact role and mechanism of ferroptosis in its pathogenesis and progression remains unclear. In this study, an experiment was conducted using different dietary lipid levels in the feeding of largemouth bass (Micropterus salmoides) for 11 weeks. The results revealed that the growth performance and whole-body protein content significantly increased with the elevation of dietary lipid levels up to 12%. The activities of antioxidant enzymes as well as the content of GSH (glutathione) in the liver initially increased but later declined as the lipid levels increased; the contents of MDA (malondialdehyde) and GSSG (oxidized glutathione) demonstrated an opposite trend. Moreover, elevating lipid levels in the diet significantly increased liver Fe2+ content, as well as the expressions of TF (Transferrin), TFR (Transferrin receptor), ACSL4 (acyl-CoA synthetase long-chain family member 4), LPCAT3 (lysophosphatidylcholine acyltransferase 3), and LOX12 (Lipoxygenase-12), while decreasing the expressions of GPX4 (glutathione peroxidase 4) and SLC7A11 (Solute carrier family 7 member 11). In conclusion, the optimal lipid level is 12.2%, determined by WG-based linear regression. Excess lipid-level diets can up-regulate the ACSL4/LPCAT3/LOX12 axis, induce hepatic oxidative stress and cell death through a ferroptotic-like program, and decrease growth performance.

A double boronic acid affinity "sandwich" SERS biosensor based on magnetic boronic acid controllable-oriented imprinting for high-affinity biomimetic specific recognition and rapid detection of target glycoproteins.

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) × 10-8M, 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 0.004ng/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 (40min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.

Anemia and Iron Profile in Hemodialysis and Nonhemodialysis Patients with Chronic Kidney Disease

Abstract BACKGROUND: Chronic kidney disease (CKD) is a global health concern, with anemia being a significant complication. Anemia in CKD patients is multifactorial and often leads to poorer outcomes. Assessing the iron profile, including serum ferritin, iron, and transferrin saturation, is crucial for identifying absolute or functional iron deficiency anemia (IDA). An objective evaluation of the iron profile is essential for effective and comprehensive management of anemia. MATERIALS AND METHODS: The study involved 100 adult patients with CKD and anemia, who were divided into two groups based on age and sex. The patients were divided into two groups: one received regular hemodialysis (HD) 2–3 times per week, whereas the other received no dialysis or dialysis infrequently. Exclusion criteria included infections, inflammation, renal injury, neoplasms, acute hemolysis, and thalassemia. RESULTS: Anemia is a common complication in patients with CKD, both those on HD and non-HD. Among the types of anemia observed, 50% of HD patients and 72% of non-HD CKD patients have normochromic anemia. In addition, 46% of HD patients and 24% of non-HD patients have IDA. Specifically, 24% of HD patients have absolute IDA and 22% have functional IDA, compared to 12% of both absolute and functional IDA in non-HD CKD patients, with a significant statistical difference between the two groups. Furthermore, serum iron and transferrin saturation levels show significant differences between HD and non-HD CKD patients. CONCLUSION: Anemia, especially IDA in CKD patients undergoing HD, requires accurate diagnosis through transferrin saturation and serum iron levels, and customized treatment based on dialysis status and anemia type is crucial.

PREVALENCE OF MALARIA, THE EFFECT OF PARASITAEMIA ON BLOOD PARAMETERS AND IRON LEVEL OF INFECTED CHILDREN UNDER FIVE YEARS OF AGE IN ITU, SOUTH-SOUTH, NIGERIA

Malaria is a devastating public health concern in Itu with varied haematological and biochemical implications. This study seeks to crystalize the prevalence of malaria, the effect of parasitaemia on some haematological parameters, and serum iron level of infected children under 5 in Itu Local Government Area, Nigeria. The study adopted a cross-sectional study involving 430 children. Blood samples were obtained from consented caregivers. Malaria prevalence and parasitaemia level were diagnosed microscopically. Haematology auto-analyzer was used to determine haematological parameters. Malaria prevalence of 41.08% was recorded in the study. The highest prevalence (42.86%) was reported among the female subjects. The difference in the infection rate between males and females was statistically significant (p&lt;0.05). The infected children tended to have significantly lower mean haemoglobin, packed cell volume, red blood cell level, lymphocyte, monocytes, and eosinophil count, (p &lt; 0.005) and a higher mean neutrophil, as well as white blood cell count (p &lt; 0.05) compared to the non-infected subjects respectively. A weak correlation between the level of parasitaemia and Hb (r= 0.108), PCV(r=0.247), RBC (r= o.074), and a weak negative with WBC (r = -0.063) was also reported. The study also recorded a higher mean serum ferritin level (648 ng/ml) compared to non-infected, lower mean serum transferrin (6.41 ng/ml) compared to normal, and mean serum iron (54.40 ng/ml) was higher than normal. It is essential to pay keen attention to the evaluation of haematological and biochemical parameters in the management of malaria infection in children living in malaria-endemic areas.

Macrophages as determinants and regulators of systemic sclerosis-related interstitial lung disease

BackgroundInterstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD (SSc-ILD) occurs more frequently in females aged 30–55 years, whereas idiopathic pulmonary fibrosis (IPF) is more prevalent in males aged 60–75 years. SSc-ILD occurs earlier than IPF and progresses rapidly. FCN1, FABP4, and SPP1 macrophages are involved in the pathogenesis of lung fibrosis; SPP1 macrophages demonstrate upregulated expression in both SSc-ILD and IPF. To identify the differences between SSc-ILD and IPF using single-cell analysis, clarify their distinct pathogeneses, and propose directions for prevention and treatment.MethodsWe performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE159354 and GSE212109, and analyzed lung tissue samples across healthy controls, IPF, and SSc-ILD. The primary measures were the filtered genes integrated with batch correction and annotated cell types for distinguishing patients with SSc-ILD from healthy controls. We proposed an SSc-ILD pathogenesis using cell–cell interaction inferences, and predicted transcription factors regulating target genes using SCENIC. Drug target prediction of the TF gene was performed using Drug Bank Online.ResultsA subset of macrophages activates the MAPK signaling pathway under oxidative stress. Owing to the lack of inhibitory feedback from ANNEXIN and the autoimmune characteristics, this leads to an earlier onset of lung fibrosis compared to IPF. During initial lung injury, fibroblasts begin to activate the IL6 pathway under the influence of SPP1 alveolar macrophages, but IL6 appears unrelated to other inflammatory and immune cells. This may explain why tocilizumab (an anti-IL6-receptor antibody) only preserves lung function in patients with early SSc-ILD. Finally, we identified BCLAF1 and NFE2L2 as influencers of MAPK activation in macrophages. Metformin downregulates NFE2L2 and could serve as a repurposed drug candidate.ConclusionsSPP1 alveolar macrophages play a role in the profibrotic activity of IPF and SSc-ILD. However, SSc-ILD is influenced by autoimmunity and oxidative stress, leading to the continuous activation of MAPK in macrophages. This may result in an earlier onset of lung fibrosis than in IPF. Such differences could serve as potential research directions for early prevention and treatment.

Isolation, characterization and antimicrobial properties of hepatopancreas lectin of the freshwater crab Oziotelphusanaga

Lectins are versatile proteins that specifically recognize and interact with sugar moieties expressed on the cell surface. The potential of lectin in drug targeting and delivery has instigated interest to identify natural lectins. Crabs have been identified as a rich source of lectin because the innate immune system is activated on encounter of pathogens and helps in the production of lectin. Although the presence of lectins in crab's hemolymph is well documented, little information about lectin in hepatopancreas, a vital organ for immunity and digestion in crustaceans, is currently available. A calcium dependent lectin (75 kDa) was purified from the hepatopancreas of the freshwater crab Oziotelphusa naga by bioadsorption and fetuin linked Sepharose 4B affinity chromatography technique. The isolated hepatopancreas lectin is calcium dependent and maximum agglutination was observed with rabbit erythrocytes. The hemagglutinating activity of the hepatopancreas lectin was effectively inhibited by sugars, such as α-lactose, GlcNAc, trehalose and NeuAc. Compared to sialylated N-glycosylated proteins including transferrin and apo transferrin, sialylated O-glycosylated proteins like fetuin exhibited stronger inhibitory effect. The ability of erythrocytes to bind hepatopancreas lectin has been diminished by desialylation of the potent inhibitor, indicating the significance of sialic acid in lectin-ligand interactions. The purified hepatopancreas lectin showed a broad spectrum of antimicrobial activity against bacteria Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, E. coli and fungi Candida albicans and Aspergillus niger. The findings of this study demonstrate the significance of hepatopancreas lectin as a multifunctional defense protein that inhibits the growth of bacteria and fungi.

Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease.

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.

Iron Status in Male Type 2 Diabetic Patients and Its Association with Their Glycemic Status

Background &amp; objective: Alteration in iron metabolism may occur in diabetic patients especially those who have poor glycemic control. Serum iron is involved in free radical formation associated with hyperglycemia and causes diabetic complications. The present study was undertaken to observe the iron status and its relation with glycemic control in male type 2 diabetic patients. Methods: This cross-sectional analytical study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from July 2017 to June 2018. A total of 48 diagnosed male type 2 diabetic patients (cases) were recruited from the Out-patient Department (OPD) of Endocrinology based on predefined eligibility criteria. Of them, 24 had good glycemic control (HbA1c level &lt; 7%) (Group B1) and 24 had poor glycemic control (HbA1c level ≥ 7%) (Group B2). To compare the outcome (serum iron status) of these diabetic patients, another 48 age- and BMI-matched healthy non-diabetic male subjects were selected from personal contact as control. While diabetes and glycemic status (fasting blood glucose level, and HbA1c) of the diabetic patients were exposure variables, serum iron, serum total iron binding capacity (TIBC), transferrin saturation, and serum ferritin were the outcome variables. Results: The mean age of the subjects of either study group was around 43 and there was no significant difference between the groups concerning age (p = 0.610). The distribution of BMI and serum creatinine between groups was also similar (p = 0.135 and p = 0.134 respectively). The cases had a significantly higher level of serum iron, transferrin saturation, and an insignificantly lower total iron binding capacity (TIBC) than their non-diabetic peers (p = 0.045, p = 0.036, and p = 0.061 respectively). A comparison of outcome variables among the three groups shows that the groups were significantly heterogeneous in terms of serum iron, TIBC, transferrin saturation, haemoglobin level (p = 0.032, p = 0.012, p = 0.008 and p = 0.018 respectively). The associations were more conspicuous in patients with poor glycemic status. Correlation analyses revealed that while there was a significant linear correlation between serum iron and HbA1c (r = + 0.376, p &lt; 0.01), it was negatively correlated with serum TIBC (r = -0.478, p &lt; 0.001). The glycemic status (HbA1c) was also found to be linearly correlated with serum ferritin and transferrin saturation (r = + 0.354, p = 0.013 and r = + 0.462, p &lt; 0.001 respectively). Conclusion: The study concluded that type 2 diabetic patients have a significantly higher level of serum iron, transferrin saturation, and a lower total iron binding capacity (TIBC) than the non-diabetic healthy subjects, all of which may lead to reduced synthesis of hemoglobin. The compromised iron metabolism is even more evident as the hyperglycemia aggravates. Ibrahim Card Med J 2023; 13 (1&amp;2): 32-39

SLC40A1-related hemochromatosis associated with a p.Y333H mutation in mainland China: a pedigree report and literature review

BackgroundHaemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including cirrhosis, diabetes, cardiomyopathy, etc. SLC40A1-related haemochromatosis is associated with gain-of-function mutations in the SLC40A1 gene, which encodes ferroportin. While sporadic reports of this condition exist in mainland China, the understanding of the phenotype and genetic pattern associated with the SLC40A1 p.Y333H mutation remains incomplete.Case presentationWe report a pedigree with heterozygous p.Y333H mutation in Chinese Han population. The proband is a 64-year-old man complaining of persistent abnormality of liver enzyme levels for 1 year, with a history of knee joint pain, diabetes and skin pigmentation. He displayed markedly elevated serum ferritin level and transferrin saturation. Magnetic resonance imaging showed iron deposition in the liver, spleen, and pancreas, along with cirrhosis and splenomegaly. Whole exome sequencing identified a heterozygous allelic variant c.997T > C (p.Y333H). Genetic screening of family members identified four first-degree relatives and three second-degree relatives having the same mutation. Additional cases with this mutation from two published studies were included. Among the probands and screened relatives, all eight males aged over 30 y had ferritin level > 1000 µg/L, transferrin saturation > 90%. Four patients with organ damage in the present study received therapeutic phlebotomy, alleviating clinical symptoms and improving in transferrin saturation and serum ferritin.ConclusionsThis study reports the largest pedigree with heterozygous SLC40A1 p.Y333H mutation in the Chinese population to date. In Chinese families, males over 30 years old with hemochromatosis due to SLC40A1 p.Y333H mutation exhibit severe iron overload phenotypes.

Revolutionizing disease diagnosis and management: Open-access magnetic resonance imaging datasets a challenge for artificial intelligence driven liver iron quantification

Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL) techniques, such as convolutional neural networks (CNNs), have emerged as transformative technologies with vast potential in healthcare. Body iron load is usually assessed using slightly invasive blood tests (serum ferritin, serum iron, and serum transferrin). Serum ferritin is widely used to assess body iron and drive medical management; however, it is an acute phase reactant protein offering wrong interpretation in the setting of inflammation and distressed patients. Magnetic resonance imaging is a non-invasive technique that can be used to assess liver iron. The ML and DL algorithms can be used to enhance the detection of minor changes. However, a lack of open-access datasets may delay the advancement of medical research in this field. In this letter, we highlight the importance of standardized datasets for advancing AI and CNNs in medical imaging. Despite the current limitations, embracing AI and CNNs holds promise in revolutionizing disease diagnosis and treatment.

Analysis of erythrocyte and iron study data among plateletpheresis donors in Hangzhou, China

BackgroundThe purpose of this study is to obtain the iron parameters level of blood donors and the population who need to pay attention to iron parameters level in this area. MethodsA total of 993 plateletpheresis donors were included in this study, including 798 males and 195 females. The results of erythrocyte and iron parameters of blood donors were compared and analyzed in different groups according to the gender, age and number of blood donations. ResultThe proportion of men and women with low serum ferritin (SF) levels was 10.8 % and 27.7 %, respectively. The mean levels of serum iron (SI), SF, transferrin saturation (Tfs), hemoglobin (Hb) and hematocrit (HCT) of male blood donors decreased with the increase of age groups, but there was no significant statistical difference between the results of female blood donors. The level of SI, SF, Tfs, Hb and HCT of male donors decreased with the increase of blood donations in the past year, while TRF and TIBC increased. The level of Hb, HCT and SF of female donors showed no significant downward trend, while the levels of TRF increased with increasing donations in the past year, excluding first-time donors. The SI of female donors trended down, and TIBC trended up with increasing donations. ConclusionBlood collection institutions need to focus on iron parameters levels in older and frequent male donors, and young fertile female donors.

Iron deposition participates in LPS-induced cognitive impairment by promoting neuroinflammation and ferroptosis in mice

Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including postoperative cognitive dysfunction (POCD). Iron deposition was proved to participate in this process. But how iron mediates inflammation-induced cognitive deficits remains unknown. This study aimed to investigate the mechanism of iron through the neuroprotective effect of the iron chelator deferoxamine (DFO) in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Adult C57BL/6 mice were pretreated with 0.5 μg of DFO three days before intracerebroventricular microinjection of 2 μg of LPS. The mice showed memory deficits by showing decreased percentage of distance and the time within the platform-site quadrant, fewer platform-site crossings, and shortened swimming distance around the platform in the Morris water maze test, which were significantly mitigated by DFO pretreatment. Mechanistically, DFO prevented LPS-induced iron accumulation and modulated the imbalance of proteins expression related to iron metabolism, including elevated transferrin (TF) levels and reduced ferritin (Fth) caused by LPS. DFO attenuated the LPS-induced lipid peroxidation and oxidative stress, which is evidenced by the decrease of malondialdehyde (MDA) and lipid peroxidation (LPO) levels and the increase of superoxide dismutase (SOD) activity and glutathione (GSH) concentration. Moreover, DFO ameliorated ferroptosis-like mitochondrial damages in the hippocampus and also alleviated the expression of ferroptosis-related proteins in the hippocampus. Additionally, DFO attenuated microglial activation, alleviated LPS-induced inflammation, and reduced elevated levels of IL-6 and TNF-α in the hippocampus. Taken together, our findings suggested that DFO exerts neuroprotective effects by alleviating excessive iron participation in lipid peroxidation, reducing the occurrence of ferroptosis, inhibiting the vicious cycle between oxidative stress and inflammation, and ultimately ameliorating LPS-induced cognitive dysfunction, providing novel insights into the immunopathogenesis of inflammation-related cognitive dysfunction and future potential prevention options targeting iron.

Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Developing innovative point-of-care electrochemical sensors empowered by cardiac troponin I-responsive nanocomposite materials

This study integrates dopamine (DA) electropolymerization, epitope imprinting, and nanomaterials (i.e., gold nanoparticles (AuNP) and graphene quantum dots (GQD)) to develop three distinct electrochemical sensors (DA-AuNP-MIP, DA-GQD-MIP, and DA-AuNP-GQD-MIP) for detecting cardiac troponin I (cTnI) with assessing their sensitivity, selectivity, and specificity profiles. The sensors exhibited high affinity for the target biomarker, enabling detection within a concentration range of 0.01–20 ng mL−1, with dissociation constants ranging from 2.7 to 69 pM. The successful fabrication of sensors was also confirmed through atomic force microscopy (AFM), scanning electron microscopy (SEM), fluorescence microscopy, contact angle measurements, cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). The cTnI selectivity assessment of imprinted nanosensors compared to their non-imprinted counterparts at 0.01–2.5 ng mL−1 showed that the DA-AuNP-GQD-MIP sensor yielded a maximum imprinting factor of 5.9. A negligible cross-reactivity for DA-AuNP-MIP and DA-AuNP-GQD-MIP sensors was found against glucose, adenovirus epitope, another cTnI epitope, bovine serum albumin (BSA), transferrin, and neuron-specific enolase (NSE). Epitope specificity at various concentrations (10–60 nM), concentration-dependent cTnI detection in human serum (0.01–10 ng mL−1) and sensor recovery rates (0.1–10 ng mL−1) in human serum were determined with the best-performing sensor (i.e., DA-AuNP-GQD-MIP). The sensor demonstrated very high epitope specificity in comparison to another cTnI epitope as well as excellent detection performances in human serum studies. The newly engineered epitope-mediated electrochemical sensing platform showcases considerable potential for precise and straightforward diagnosis of coronary artery diseases, aiming to materialize a cost-effective Point-of-Care Testing (POCT) system.

Hematological parameters of healthy pregnant women in three trimesters compared with parameters of non-pregnant women

Anemia is a public health problem, especially in developing countries. All over the world iron deficiency is the main cause of anemia, especially during pregnancy. Pregnant women belong to the most vulnerable population group in Iraq.The objective: to determine the impact of pregnancy on hematological parameters and to compare the hematological indicators in different periods of gestation with the indicators of non-pregnant women.Materials and methods. The study was conducted over a three-month period at Baghdad hospitals and medical centers, including Baghdad Teaching Hospital, Al-Karam Hospital, and a health center in Al-Dorrah and Al-Shaab, Baghdad province, from September 1 to December 1, 2022. 60 pregnant women, 20 persons in each trimester, and 25 non-pregnant women (control) aged 18–35 years were included in the study. All participants were examined for hematological parameters: hemoglobin, erythrocytes, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), measured of the concentration of hemoglobin in red blood cells (MCHC) and determined the level of iron in the blood (serum iron – SI, total iron binding capacity – TIBC, transferrin saturation – TS and serum ferritin – SF).Results. A significant decrease in the hematological indicators of pregnant women in the first trimester of pregnancy compared to non-pregnant women was established – hemoglobin, erythrocytes, PCV, MCH, MCHC. The dynamics of the decrease in the level of these parameters increases in the second trimester, and also progressively decreases in the third trimester, which leads to anemia.Starting from the first trimester and during the second and third trimesters, a decrease in the level of serum iron, transferrin saturation and serum ferritin was found in pregnant women compared to non-pregnant women, but the level of TIBC increased. During the second trimester, the need for iron begins to increase and continues to growth until the end of pregnancy. In addition, these research results indicate the importance of iron deficiency in the development of iron deficiency anemia.Conclusions. During pregnancy, anemia and a decrease in the level of some hematological parameters were determined, which progresses with increasing gestational age and is less compared to that in non-pregnant women. A decrease in the level of iron in the blood serum was established from the first to the third trimester of pregnancy. The severity of anemia is related to many factors, especially age, education level, low income, type of diet and parity.