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Hemoglobin is an oxygen-transport protein in red blood cells that interacts with multiple ligands, e.g., oxygen, carbon dioxide, carbon monoxide, and nitric oxide. Genetic variations in hemoglobin chains, such as those underlying sickle cell disease and thalassemias, present substantial clinical challenges. Here, we review the progress in research, including the use of allosteric modulators, pharmacological chaperones, and antioxidant treatments, which has begun to improve hemoglobin stability and oxygen affinity. According to UniProt (as of 7 August 2024), 819 variants of the α-hemoglobin subunit and 771 variants of the β-hemoglobin subunit have been documented, with over 116 classified as unstable. These data demonstrate the urgent need to develop variant-specific stabilizing options. Beyond small-molecule drugs/binders, novel protein-based strategies—such as engineered hemoglobin-binding proteins (including falcilysin, llama-derived nanobodies, and α-hemoglobin-stabilizing proteins)—offer promising new options. As our understanding of hemoglobin's structural and functional diversity grows, so does the potential for genotype-driven approaches. Continued research into hemoglobin stabilization and ligand-binding modification may yield more precise, effective treatments and pave the way toward effective strategies for hemoglobinopathies. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia (IDA) and the β-thalassemia trait (BTT) are two main causes of hypochromic–microcytic anemia worldwide. Researchers have described many red blood cell (RBC) indices as screening tests for presumptive differentiation, based on differences observed in complete blood count (CBC) data for each condition. There are few BTT reports in Chile, and neither laboratories nor clinical staff have widely used these indices. Objective: The objective of this study was to evaluate the diagnostic performance of 29 RBC indices in 182 patients (51 BTT and 131 IDA) and compare CBC results in both groups. Methods: A retrospective search was carried out in the Laboratory Information System between January 2021 and February 2024 to collect results from CBC, and 29 RBC indices were calculated for each patient. Then, sensitivity, specificity, positive predictive value, negative predictive value, Youden's index, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy were calculated using MedCalc©. Results: The Green and King, Wongprachum, and Keikhaei indices showed the best discriminatory power with Youden index values of 0.923, 0.908, and 0.896, respectively, and significant differences were observed in all CBC parameters between BTT and IDA patients (p < 0.001). Conclusions: The Green and King, Wongprachum, and Keikhaei indices showed the best performance; therefore, they can be used as screening for the differential diagnosis between BTT and IDA in order to improve diagnosis given the important therapeutic and epidemiological implications. In this way, clinical laboratories could have a main role in the investigation of these patients. [ABSTRACT FROM AUTHOR]

Maize is the staple food crop for millions of people in sub-Saharan Africa. Iron (Fe) and zinc (Zn) deficiency is a significant health risk that mainly affects low-income populations who rely solely on maize-based diets. This problem can be alleviated by developing micronutrient-rich maize grain. The aim of this study was to determine the adaptation and performance of hybrids for Fe and Zn concentration and grain yield under low soil nitrogen (N) and optimal conditions. Eighteen hybrids derived from lines and testers with low, medium, and high Fe and Zn concentration were grown during the summer rainy seasons of 2017 and 2018 at three locations under low and optimal N conditions. There were significant genotype and environment effects for grain yield, and Fe and Zn concentration, but the genotype by environment interaction effects were the largest, accounting for between 36% and 56% of variation under low N conditions. Low N levels significantly reduced grain yield, and Fe and Zn concentration. Hybrids G1, G2, G4, G7, G10, G11, and G16 were relatively stable, with relatively high mean Fe and Zn concentrations, and low additive main effects and multiplicative interaction (AMMI) stability values and iron stability index (FSI) and zinc stability index (ZSI) under low N conditions. These genotypes can be considered for production under low N stress conditions. Two environments (E4 and E3) were identified for good discriminatory power for genotype performance in terms of Fe and Zn content, respectively. Stable and high-yielding genotypes with high Fe and Zn concentration can be used as biofortified hybrids, which can contribute to a sustainable solution to malnutrition in the region, especially under low N conditions. [ABSTRACT FROM AUTHOR]

(1) Background: Alpha (α)-thalassaemia is a genetic disorder that affects 5% of the world population. Deletional or nondeletional mutations of one or both HBA1 and HBA2 on chromosome 16 will result in reduced production of α-globin chains, a component of haemoglobin (Hb) that is required for the formation of red blood cells (RBCs). This study aimed to determine the prevalence, haematological and molecular characterisations of α-thalassaemia. (2) Method: The parameters were based on full blood count, high-performance liquid chromatography and capillary electrophoresis. The molecular analysis involved gap-polymerase chain reaction (PCR), multiplex amplification refractory mutation system-PCR, multiplex ligation-dependent probe amplification and Sanger sequencing. (3) Results: With a total cohort of 131 patients, the prevalence of α-thalassaemia was 48.9%, leaving the remaining 51.1% with potentially undetected α gene mutations. The following genotypes were detected: -α3.7/αα (15.4%), -α4.2/αα (3.7%), --SEA/αα (7.4%), αCSα/αα (10.3%), αAdanaα/αα (0.7%), αQuong Szeα/αα (1.5%), -α3.7/-α3.7 (0.7%), αCSα/αCSα (0.7%), -α4.2/αCSα (0.7%), –SEA/αCSα (1.5%), –SEA/αQuong Szeα (0.7%), -α3.7/αAdanaα (0.7%), --SEA/-α3.7 (2.2%) and αCSα/αAdanaα (0.7%). Indicators such as Hb (p = 0.022), mean corpuscular volume (p = 0.009), mean corpuscular haemoglobin (p = 0.017), RBC (p = 0.038) and haematocrit (p = 0.058) showed significant changes among patients with deletional mutations, but not between patients with nondeletional mutations. (4) Conclusions: A wide range of haematological parameters was observed among patients, including those with the same genotype. Thus, a combination of molecular technologies and haematological parameters is necessary for the accurate detection of α-globin chain mutations. [ABSTRACT FROM AUTHOR]

Risk assessment and developing predictive models for diabetes prevention is considered an important task. Therefore, we proposed to analyze and provide a comprehensive analysis of the performance of diabetes screening scores for risk assessment and prediction in five populations: the Chinese, Japanese, Korean, US-PIMA Indian, and Trinidadian populations, utilizing statistical and machine learning (ML) methods. Additionally, due to the present COVID-19 epidemic, it is necessary to investigate how diabetes and COVID-19 are related to one another. Thus, by using a sample of the Korean population, the interrelationship between diabetes and COVID-19 was further investigated. The results revealed that by using a statistical method, the optimal cut points among Chinese, Japanese, Korean, US-PIMA Indian, and Trinidadian populations were 6.205 mmol/L (FPG), 5.523 mmol/L (FPG), and 5.375% (HbA1c), 150.50–106.50 mg/dL (FBS), 123.50 mg/dL (2hPG), and 107.50 mg/dL (FBG), respectively, with AUC scores of 0.97, 0.80, 0.78, 0.85, 0.79, and 0.905. The results also confirmed that diabetes has a significant relationship with COVID-19 in the Korean population (p-value 0.001), with an adjusted OR of 1.21. Finally, the overall best ML models were performed by Naïve Bayes with AUC scores of 0.736, 0.75, and 0.83 in the Japanese, Korean, and Trinidadian populations, respectively. [ABSTRACT FROM AUTHOR]

In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the "Control Population", which enabled standardization of protein serum levels according to age and sex (N = 27,382); the "NAFLD-Biopsy" cohort for associations with liver features (N = 926); and the USA "NAFLD-Serum" cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in "NAFLD-Biopsy", and before and during COVID-19 pandemic peaks in "NAFLD-Serum". Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19. [ABSTRACT FROM AUTHOR]

Iron is required for energy production, DNA synthesis, and cell proliferation, mainly as a component of the prosthetic group in hemoproteins and as part of iron-sulfur clusters. Iron is also a critical component of hemoglobin and plays an important role in oxygen delivery. Imbalances in iron metabolism negatively affect these vital functions. As the crucial barrier between the fetus and the mother, the placenta plays a pivotal role in iron metabolism during pregnancy. Iron deficiency affects 1.2 billion individuals worldwide. Pregnant women are at high risk of developing or worsening iron deficiency. On the contrary, in frequent hemoglobin diseases, such as sickle-cell disease and thalassemia, iron overload is observed. Both iron deficiency and iron overload can affect neonatal development. This review aims to provide an update on our current knowledge on iron and heme metabolism in normal and pathological pregnancies. The main molecular actors in human placental iron metabolism are described, focusing on the impact of iron deficiency and hemoglobin diseases on the placenta, together with normal metabolism. Then, we discuss data concerning iron metabolism in frequent pathological pregnancies to complete the picture, focusing on the most frequent diseases. [ABSTRACT FROM AUTHOR]

Lentil grains with high nutritional value qualify as a promising candidate for alleviation of micronutrient malnutrition in South Asia and North Africa. Genetic variation for micronutrient concentration in germplasm is prerequisite for biofortification of this crop. In the present study, ninety-six lentil genotypes consisting of Indian (released varieties, advanced breeding lines and germplasm lines) and Mediterranean (germplasm lines and landraces) lines were evaluated for grain iron (Fe) and zinc (Zn) concentrations and the stability of these traits was studied across three different locations in India. The pooled analysis of variance revealed significant genotype, environment and genotype by environment interaction (GEI) mean squares for both the micronutrients. Stability analysis employing the AMMI model elucidated the first two interaction principal components as significant and cumulatively explained 100% of GEI variation. The first two components explained 55.9% and 44.1% of the GEI sum of squares for grain iron and 50.8% and 49.2% for grain zinc concentration, respectively. No correlation between grain iron and zinc concentration was observed. Among 96 lines, genotypes IG 49, P 16214, ILL 147 and P 2118 were found to be relatively stable, having higher mean iron and zinc concentrations with low modified AMMI stability value (MASV), modified AMMI stability index (MASI) and genotype selection index (GSI). The identified promising genotypes (high Fe: P 16214, IG 115, P 2127 and IC 560812 and high Zn: P 8115, P 3234, LL 461 and IC 560812) can be utilized for studying the genetics of grain Fe and Zn concentration by developing mapping populations and for biofortification of Indian lentil. [ABSTRACT FROM AUTHOR]

Background: Micronutrient malnutrition is a form of undernutrition that causes diseases, and this is mainly due to insufficient intake of nutrients in daily foods. The status of micronutrients for people in Sudan remains scarce, and information is limited. The aim of this study is to highlight the status of micronutrients among women of reproductive age (15–49 years of age) and their children in Sudan. Methods: This manuscript is a quantitative descriptive study, based on the data from Sudan Micronutrient Survey (SMS); it is part of the second round of the Simple Spatial Survey Method (S3M II) in Sudan (a total of 93,882 households). Results: The level of consumption of vitamin A-rich foods was found to be moderate at 67.36% for reproductive-age women and low at 23.44% for under-five children. Similarly, consumption rate of vitamin B-rich foods among reproductive-age women was 62.13%, and low for children at 11.02%. The consumption of iron-, calcium-, and zinc-rich foods was moderate among women (66.75%, 47.69%, 69.72%, respectively) and very low in children (12.28%, 17.62%, 14.99%, respectively). The iron deficiency prevalence was 47% in non-pregnant women, 58% in pregnant women, and 54% in children. The prevalence of anemia was 30% in non-pregnant women, 37% in pregnant women, and 48% in children. Generally, urinary iodine concentration was inadequate in lactating and non-pregnant women as well as in pregnant women. Most indicators of micronutrients in Sudan for children and women of reproductive age were highly significant. Sudan needs more efforts to create an enabling environment through legislation, policies, and strategies to strengthen the nutrition-sensitive and specific interventions and improving status of micronutrients among women and children, focusing on food fortification, food supplements, and counseling on micronutrients intake for mothers during antenatal and postnatal services as well as raising community awareness. [ABSTRACT FROM AUTHOR]