Transferrin Research Articles

Effect of lactose on the in vitro development of sheep secondary follicles

Considering that follicular development is an energy-dependent process, supplementation of the culture medium with energy substrates, such as lactose, would improve follicle viability and growth. Thus, the aim of this study was to evaluate the effect of lactose on morphology, development, glutathione (GSH) concentration, mitochondrial activity, DNA fragmentation, and meiotic resumption of oocytes from sheep secondary follicles cultured in vitro. Secondary follicles were isolated from the cortex of ovine ovaries and cultured individually for 18 days in α-MEM supplemented with bovine serum albumin (BSA), insulin, glutamine, hypoxanthine, transferrin, selenium and ascorbic acid (control medium: α-MEM+) or in α-MEM+ plus different concentrations of lactose (0.025, 0.05 and 0.1 M). After culture, some of the oocytes were subjected to TUNEL assay and in vitro maturation (IVM). Follicular morphology, glutathione (GSH) concentration and mitochondrial activity were evaluated at the end of the culture. At the day 18, the percentage of morphologically normal follicles was greater (P<0.05) in the treatment of 0.025 M lactose (92.5 %) compared to the control group (75.55 %). In addition, GSH concentrations increased (P<0.05) in treatment containing 0.025 M lactose compared to the other treatments. Furthermore, oocytes cultured in 0.025 M lactose had greater (P<0.05) mitochondrial activity levels than in α-MEM+ and 0.1 M lactose. The group α-MEM+ presented a increase of TUNEL-positive oocytes (35.09 %) compared to 0.025 lactose (9.09 %). The percentage of meiotic resumption was greater (P<0.05) in oocytes from secondary follicles cultured in 0.025 M lactose (54.5 %) than in α-MEM+ (45.5 %). In conclusion, 0.025 M lactose improved survival, GSH and active mitochondria levels and meiotic resumption of oocytes from in vitro cultured secondary follicles. Supplementation of the culture medium of preantral follicles with lactose can gradually provide energy to follicular cells, potentially enhancing the production of viable oocytes for biotechniques such as IVM and in vitro fertilization.

The Diagnostic Performance of Serum Glycosylated Ferritin in Patients Undergoing Regular Blood Transfusion: An Indicator of Iron Overload to Initiate Iron Chelation Therapy.

Background and objective Serum ferritin concentration and transferrin saturation are commonly employed to estimate body iron but are non-specific to iron overload. Glycosylated ferritin may be primarily elevated in cases of iron overload in patients undergoing regular blood transfusions. In this study, we aimed to estimate glycosylated ferritin and determine its cutoff values for iron overload in patients receiving blood transfusions regularly. We also endeavored to the examine correlation between serum ferritin and glycosylated ferritin in patients receiving regular blood transfusions. Methods We conducted a cross-sectional study involving 17 patients undergoing regular blood transfusions in the Department of Medical Oncology/Hematology, who had already received ≥10 transfusions without any iron chelation therapy or acute inflammation. All participants were evaluated based on a questionnaire to gather relevant medical details. Serum iron, ferritin, glycosylated ferritin, and unsaturated iron-binding capacity (UIBC) were estimated. Total iron-binding capacity (TIBC) and transferrin saturation were also calculated. Results Participants were divided into two groups based on transferrin saturation (≥50% as a reference for iron overload). The group with transferrin saturation ≥50% had significantly higher levels of serum ferritin, glycosylated ferritin, and iron, compared to the group with transferrin saturation <50%. Glycosylated ferritin showed a positive correlation with ferritin (rho=0.80) and transferrin saturation (rho=0.64), which was statistically significant. UIBCand TIBCshowed a negative association with glycosylated ferritin. The correlation of glycosylated ferritin with units of blood transfusion (Spearman's rho=0.60) was found to be better than that of serum ferritin (Spearman's rho=0.52). Conclusions Based on our findings, glycosylated ferritin could be a potential marker for transfusion-related iron overload. The optimal cutoff value for iron overload using serum glycosylated ferritin level was >587.55 ng/mL. Further extensive studies withlarger sample sizes will substantiate the role of glycosylated ferritin in predicting post-transfusion iron overload.

Association between iron metabolism markers and triglyceride-glucose index: A cross-sectional study in China Health and Nutrition Survey.

Iron metabolism plays an important role in insulin resistance, and the triglyceride-glucose (TyG) index has been proposed in recent years as a more accessible and cost-effective marker for insulin resistance. This study aims to evaluate the association between iron metabolism markers, including ferritin (FER), transferrin (TRF), and transferrin receptor (TFR), and the TyG index. A total of 6524 Chinese individuals aged between 18 and 75 years were included in this study. Multivariable linear models were used to investigate the association between FER, TRF, and TFR levels, and the TyG index. Further subgroup analyses stratified by age and sex were also performed. There was a positive association between FER and TRF levels and the TyG index in all 3 multivariable linear regression models, regardless of stratification by sex and age. Additionally, TFR was positively associated with the TyG index among females and those aged ≥45 years, but not among males and those aged <45 years. Our findings reveal a positive association between FER and TRF levels and the TyG index in a Chinese population, while the association between TFR levels and the TyG index showed different patterns depending on age and gender.

Correlation between erythrocyte parameters and iron status in cyclic Spanish Purebred mares.

The aim of this study was to evaluate the serum iron status and its relation to hematological indexes in cyclic mares. Blood samples were taken from 40 Spanish Purebred mares on days - 5, 0, + 5 and + 16 of their cycle. Concentration of transferrin (TRF) was significantly lower on day 0 than on days + 5 and + 16, transferrin saturation (TSAT) decreased significantly on days 0 and + 16 compared to day - 5, total iron-binding capacity (TIBC) on day + 16 was significantly higher than those on days - 5 and 0, and on day + 5 it was also significantly higher than that on day 0, unsaturated iron-binding capacity (UIBC) was reduced on day + 16 compared to days - 5 and 0, red blood cell (RBC) count on day + 16 was higher than that on days - 5 and 0 (p < 0.05), with no differences in the concentration of hemoglobin (HB) and packed cell volume (PCV). TRF and TIBC (r = 0.95), RBC and HB (r = 0.64), RBC and PCV (r = 0.78), and HB and PCV (r = 0.63) were positively and significantly correlated (P < 0.05). The estrous cycle in the Spanish Purebred mare is characterized by an increase in TRF and TIBC during the follicular phase and an increase in TSAT, UIBC and RBC in the luteal phase, without changes in other hematological parameters. The coordinated activity of these parameters guarantees an adequate iron (Fe) transfer and utilization during follicular development, ovulation, and the luteal period in the mare. Therefore, the estrous cycle must be considered in the evaluation of the mare's iron status, in light of significant changes observed both in early and at late luteal phases. The magnitude of these changes and the meaning to the physiology of the mares showed that in cyclic mares, hematological parameters and indicators of iron status evolve differently depending on the phase of the cycle, and their interpretation can help to veterinarians involved in equine practice.

Elucidating PAR1 as a therapeutic target for delayed traumatic brain injury: Unveiling the PPAR-γ/Nrf2/HO-1/GPX4 axis to suppress ferroptosis and alleviate NLRP3 inflammasome activation in rats

Repetitive traumatic brain injury (RTBI) is acknowledged as a silent overlooked public health crisis, with an incomplete understanding of its pathomechanistic signaling pathways. Mounting evidence suggests the involvement of thrombin and its receptor, the protease-activated receptor (PAR)1, in the development of secondary injury in TBI; however, the consequences of PAR1 modulation and its impact on ferroptosis-redox signaling, and NLRP3 inflammasome activation in RTBI, remain unclear. Further, the utilitarian function of PAR1 as a therapeutic target in RTBI has not been elucidated. To study this crosstalk, RTBI was induced in Wistar rats by daily weight drops on the right frontal region for five days. Three groups were included: normal control, untreated RTBI, and RTBI+SCH79797 (a PAR1 inhibitor administered post-trauma at 25 μg/kg/day). The concomitant treatment of PAR1 antagonism improved altered behavior function, cortical histoarchitecture, and neuronal cell survival. Moreover, the receptor blockade downregulated mRNA expression of PAR1 but upregulatedthat of the neuroprotective receptor PPAR-γ. The anti-inflammatory impact of SCH79797 was signified by the low immune expression/levels of NF-κB p65,TNF-α, IL-1β, and IL-18. Consequently, the PAR1 blocker hindered the formation of inflammasome components NLRP3, ASC, and activated caspase-1. Ultimately, SCH79797 treatment abated ferroptosis-dependent iron redox signaling through the activation of the antioxidant Nrf2/HO-1 axis and its subsequent antioxidant machinery (GPX4, SOD) to limit lipid peroxidation, iron accumulation, and transferrin serum increment. Collectively, SCH79797 offered putative preventive mechanisms against secondary RTBI consequences in rats by impeding ferroptosis and NLRP3 inflammasome through activating the PPAR-γ/Nrf2 antioxidant cue.

Exploring genetic association of systemic iron status and risk with incidence of diabetic neuropathy

BackgroundDiabetic 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.MethodsWe 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.ResultsNo 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.ConclusionWhile 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.

Population Screening for Hereditary Haemochromatosis-Should It Be Carried Out, and If So, How?

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted to be polygenic or at least gene-environment modified. Hereditary haemochromatosis (HH) is an inherited iron overload disorder, for which the vast majority of affected individuals (>90%) have homozygosity for a single pathogenic variant in the HFE gene, resulting in p.Cys282Tyr. Further, there is significant benefit to an individual in identifying the genetic risk of HH, since the condition evolves over decades, and the opportunity to intervene and prevent disease is both simple and highly effective through regular venesection. Add to that the immediate benefit to society of an increased pool of ready blood donors (blood obtained from HH venesections can generally be used for donation), and the case for population screening to identify those genetically at risk for HH becomes more cogent. Concerns about genetic discrimination, creating a cohort of "worried well", antipathy to acting on medical advice to undertake preventive venesection or simply not understanding the genetic risk of the condition adequately have all been allayed by a number of investigations. So why then has HH population genetic screening not been routinely implemented anywhere in the world? The answer is complex, but in this article we explore the pros and cons of screening for HH and the different views regarding whether it should be phenotypic (screening for iron overload by serum ferritin and/or transferrin saturation) or genotypic (testing for HFE p.Cys282Tyr). We argue that now is the time to give this poster child for population genetic screening the due consideration required to benefit the millions of individuals at risk of HFE-related iron overload.

Plasma amino acid profiles in thalassaemia major with iron overload

Introduction: Iron overload in thalassaemia major patients mainly occurs due to periodic transfusions. When iron exceeds transferrin capacity, non-transferrin bound iron accumulates and causes tissue damage, including in the gastrointestinal tract, resulting in impaired enterocyte function and amino acid absorption. The aim of this study was to evaluate amino acid profiles in patients with thalassaemia major after repeated transfusions and chelation. Methods: Whole blood amino acids were analysed from dried blood spots using liquid chromatography tandem mass spectrometry. This study consisted of two parts: a cross-sectional and a cohort study in thalassaemia-β-major patients. In the cross-sectional study, amino acid profiles were analysed in 219 thalassaemia patients who received routine transfusion and chelation therapy, and 60 healthy control subjects. The cohort study included 21 subjects, from whom blood samples were taken at pre-transfusion, 1-day posttransfusion, one and three months post-chelation to evaluate changes in amino acid levels. Results: There were significant differences between amino acid levels in thalassaemia subjects and controls. Positive correlations were found between serum iron and transferrin with age, also between transferrin with proline, valine, phenylalanine, aspartic acid, and glutamic. Phenylalanine and aspartic acid were significantly lower in subjects with transferrin lower than 180 µg/dL. Significant correlations were found between haemoglobin with essential and non-essential amino acid groups. From the cohort study, significant changes were observed in glycine, alanine, leucine, and aspartic acid. Conclusion: Amino acid profiles in thalassaemia patients differed compared to healthy controls, even after transfusion and chelation. Phenylalanine and aspartic acid were significantly lower in subjects with low transferrin levels.

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.