Hemoglobin Molecule Research Articles

Unbinding of Alpha Chain of Hemoglobin in Sickle and Normal Structures

Abstract Sickle cell disease, a genetic disorder, is caused by a mutation of glutamic acid into valine in the β chain of hemoglobin at the sixth residue, resulting in structural change of the entire hemoglobin molecule into a sickle shape. We investigated the atomic level interaction between the α chain (chain A) and the remaining three chains to identify the structural modification in sickle hemoglobin using the molecular dynamics simulations. H-bond, solvent accessible surface area (SASA), hydrophobic interactions, salt bridges of sickle and normal hemoglobin have been estimated. The estimated parameters from sickle hemoglobin are compared to normal hemoglobin structure. Steered molecular dynamics (SMD) is utilized to estimate the force required in breaking hydrogen bonds in given chains. The SMD simulations at different pulling velocities show that the decoupling forces depend on values of pulling force. This relation is linear, 6780 pN to 12345 pN with pulling velocities of 0.00020 nm/ps to 0.00040 nm/ps in sickle hemoglobin. Much higher force of 8738 pN to 16557 pN in normal is required in normal hemoglobin with same spring constants values from k = 500 to 1100 kcal mol-1 nm-2 and same pulling velocities.

A Mathematical Model for Inducing Delays in Transmissions of Information Between Spinors Within the Heart, Hemoglobin Molecules and Cells by Mobile Waves

Biological systems like the heart, hemoglobin and cells are built from entangled spinors. Entangled spinors exchange information through two ways: (i) Spinor waves with the velocity of infinity; and (ii) Photons with the limited velocity of the speed of light. If any spin in a pair reverses, then the other spin changes sogn immediately. However, initial exchanged photons do not understand these changes, and retain the memory of the previous stage. Thus, when they reach the spinors, the spinors repel them. With time, the new emitted photons from the spinors obtain the correct information, and absorb other spinors in a pair. This repelling and absorbing causes the oscillation of heart cells and the motions of blood cells including hemoglobin. These molecules transmit information and oxygen and pass them on to cells. A mobile wave could break the entanglement between the spinors of the hemoglobin, and cause a delay in information and oxygen transmission from the heart to some cells, thereby creating non-normal cells like tumor ones. The reason for this is that without information, cells have to act independently of other cells. Also, without oxygen, cells have to use other mechanisms for respiration like the ones which were used by tumor cells in the Warburg proposal. This does not depend on the wavelength because the wavelength only determines the probability of existence of photons at each point and waves with any wavelength (even bigger than cell size) are formed from many photons with smaller size than cells. However, after some time, after establishing electromagnetic towers, the spinor structure of the body could resist these wave-fronts, and the probability for the emergence of tumors decreases. Without this resistance and according to the Warburg proposal, generated tumor cells produce different numbers of spinors which help them to diagnose the motion of T-cells, making them ready to respond. To avoid this event, we may use again some mobile waves which produce some noise around tumor cells.

PSYCHOSOCIAL FACTORS ASSOCIATED WITH MAJOR THALASSEMIA

Thalassemia is a hereditary condition that results in the creation of defective haemoglobin molecules. Patients are diagnosed with thalassemia major after exhibiting severe clinical symptoms and profound anaemia. This study aims to investigate the major thalassemia and psychosocial aspects of it, which is a critical issue, in order to serve as a road map for better treating these patients and contribute to the literature. This study used narrative review as its method. Between 2018 and 2023, a literature review was undertaken by searching materials published in databases such as Web of Science, PubMed, Scopus, and the Google Scholar search engine. Additionally, the WHO website was searched. Thalassemia major harms the heart, liver, lungs, and endocrine organs due to anaemia and iron buildup. Furthermore, the patient could experience. Mental and social issues arise as a result of the disease's congenital aetiology and lifelong duration. Thalassemia patients face significant emotional challenges as well as therapeutic burden. There are numerous research on the prevalence and physical implications of thalassemia. However, there are insufficient papers and studies documenting the psychosocial impacts of thalassemia on patients and what may be done to mitigate these effects. As a result, this research focuses on the process of thalassemia and the psychosocial problems it causes in order to contribute to the literature and provide a road map for better managing these individuals

Treating Sickle Cell Disease: Gene Therapy Approaches.

Sickle cell disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin molecules and thus distortion (sickling) of the red blood cells. SCD causes chronic pain and organ damage and shortens life expectancy. Gene therapy emerges as a potentially curative approach for people with SCD who lack a matched sibling donor for hematopoietic stem cell transplantation. Here, we review recent progress in gene therapy for SCD and focus on innovative technologies that target the genetic roots of the disease. We also review the challenges associated with gene therapy, including oncogenic risks, and the need for refined delivery methods. Despite these hurdles, the rapidly evolving landscape of gene therapy for SCD raises hope for a paradigm shift in the treatment of this debilitating disease. As research progresses, a deeper understanding of the molecular mechanisms involved and continuous improvements in gene-editing technologies promise to bring gene therapy for SCD closer to mainstream clinical application, offering a transformative, curative option for patients with this genetic disorder.

The Association Between Sickle Cell Anemia and Cognitive Dysfunction: A Systematic Review.

A kind of hemoglobinopathy known as sickle cell anemia (SCA) is characterized by aberrant hemoglobin molecules. The most frequent neurological side effects linked to SCA include neurocognitive dysfunction, asymptomatic cerebral infarction, and ischemic stroke.This study aims to investigate the relationship between SCA and cognitive dysfunction.We systematically searched electronic databases like PubMed, MEDLINE, Science Direct, and Scopus. Two independent reviewers screened and extracted data from eligible studies.Eighteen studies, including 2,457 participants in total and nearly half of them 1,151 (46.8%) were males, were included in our data. The prevalence of cognitive dysfunction in the adult population ranged from 11.5% to 70%. Cognitive dysfunction among adults was significantly associated with poorer educational status, reduced family income, decreased kidney function, older age, stroke history, and vasculopathy. The prevalence of cognitive dysfunction in children ranged from 10.2% to 68.2%. The decline in cognitive function among adults was significantly associated with children over the age of four, abnormal transcranial Doppler and previous stroke, school absence, age beyond 13, and increased BMI.Cognitive function deficiencies are a defining feature of SCA that affects people of all ages. These findings suggest that if cognitive decline is not slowed down, or better still, stopped, medical interventions targeting a variety of sequelae in this population will be ineffective. Future analyses of this population's cognition should evaluate the environmental and other biological variables.

Analysis of the Haematological Phenotype and Molecular Characteristics of Rare Abnormal Haemoglobin.

Haemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China. Peripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High-performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing. The research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg. We confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics.

Predictors of the efficacy of vedolizumab in patients with ulcerative colitis.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Voxelotor (GBT440) in pediatric sickle cell disease: A review

Sickle cell disease (SCD) was first described in 1910 in African Americans, and the mutant hemoglobin S (HbS) was identified by electrophoresis in 1948. Sickle cell disease is the first genetic disease to be molecularly defined - a single point mutation in the β-globin gene (GAG→GTG) results in substitution of valine for glutamic acid at amino acid residue 7 (including the starting methionine). Pharmacological intervention to correct the defect at a molecular/protein level has proven complex. The only established curative therapy is hematopoietic stem cell transplantation, with recent gene therapy approvals providing hope for the same. Herein, we discuss voxelotor, a drug designed to reverse the hemoglobin polymerization defect caused by the β7Glu > Val substitution in the hemoglobin molecule.

CRISPR-Cas9 Gene Editing Therapy, a Curative Hope for Sickle Cell in Nigeria, West Africa

Sickle cell anaemia is one of the haemoglobin abnormalities resulting from a genetic mutation— it is caused by inheriting two faulty genes that result in an abnormal substitution of glutamate for valine on the beta chain of haemoglobin, which causes haemoglobin molecules to stick together. According to a World Health Organization (WHO) report, 20 out of every 1,000 births suffer from sickle-cell anaemia, and 24% of Nigerians are carriers of this mutant gene. Scientists have suggested several solutions, including stem cell transplantation and gene therapies, but these have faced opposition due to ethical beliefs, high cost, and the ensuing immune issues. Research is now centered on advancing genome editing techniques for gene therapy. Ongoing studies have proven that genetic differences can be corrected methodically by modifying the genome at specific sites instead of introducing a new copy of the affected gene into the cells; due to the effectiveness of this method, scientists are testing its applications in manipulating genes in various systems. This review correlates a few studies that used the recently developed technique—CRISPR-Cas9—as a novel approach to gene therapy, dissecting the different clinical studies about sickle cell origin to point out many of its ethical and medical limitations, the consequences of these limitations, and the advancements this technology has made possible.

Studies of Light Scattering by Hemoglobin Molecules under the Effect of Iron (III) Chloride and Various pH Levels

A lot of literature sources discuss diseases associated with the hemoglobin protein [1, 2]. In the modern world, more than 800 million people suffer from anemia [3]. Assessing the level of hemoglobin in the circulatory system is one of the ways to diagnose anemia. Hemoglobin protein is also a promising source of bioactive peptides [4]. The aim of the work was to identify the reasons leading to conformation changes of this protein. It still remains unclear what exactly causes disruption of its functionality. Human hemoglobin from Sigma H7379 was studied in the work; all experiments were conducted on a dynamic light scattering spectrometer — Photocor Complex. Experimental data were obtained using optical methods of static and dynamic light scattering. The work included an analysis of the behaviour of hemoglobin protein molecules in aqueous and aqueous-saline solutions with changes in solution parameters (pH, addition of iron chloride III). At values of pH< (3.56±0.15) and pH> (10.4±0.2), the hemoglobin molecule underwent conformational changes, resulting in the disintegration of the quaternary structure into αβ−dimers and individual α− and β−globules. As a result of the study, it was found that the addition of FeCl3 to aqueous solutions of hemoglobin increases the size and mass of scattering particles, which can be explained by the adsorption of Fe3+ ions on the protein surface. However, upon reaching a certain concentration of FeCl3, the pH of the solution was lowered to such an extent that it caused conformational changes in hemoglobin, leading to the disintegration of its quaternary structure. These results can be taken into account when creating medicinal drugs for the treatment of anemia and other diseases associated with the hemoglobin protein.

The features analysis of hemoglobin expression on visual information transmission pathway in early stage of Alzheimer’s disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

The Application of Clinical and Molecular Diagnostic Techniques to Identify a Rare Haemoglobin Variant.

Haemoglobin disorders represent a heterogeneous group of inherited conditions that involve at least one genetic abnormality in one or more of the globin chains, resulting in changes in the structure, function, and/or amount of haemoglobin molecules, which are very important for their related clinical aspects. Detecting and characterizing these disorders depends primarily on laboratory methods that employ traditional approaches and, when necessary, newer methodologies essential for solving a number of diagnostic challenges. This review provides an overview of key laboratory techniques in the diagnosis of haemoglobinopathies, focusing on the challenges, advancements, and future directions in this field. Moreover, many haemoglobinopathies are benign and clinically silent, but it is not uncommon to find unexpected variants during routine laboratory tests. The present work reported a rare and clinically interesting case of identification of haemoglobin fractions in an adult man by the determination of glycated haemoglobin (HbA1c) during a routine laboratory assessment, highlighting how the correct use of laboratory data can modify and improve the patient's clinical management.

The Role of Ergothioneine in Red Blood Cell Biology: A Review and Perspective.

Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a "storage lesion" in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial "nutraceutical." Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine's potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality.

Studies of Light Scattering by Hemoglobin Molecules under the Effect of Iron (III) Chloride and Various pH Levels

Studies of Light Scattering by Hemoglobin Molecules under the Effect of Iron (III) Chloride and Various pH Levels

GLYCOSYLATED HAEMOGLOBIN: A SURROGATE MARKER FOR DYSLIPIDEMIA AND GLYCEMIC INDEX IN TYPE 2 DIABETES MELLITUS SUBJECTS

Glycosylated haemoglobin is the substance formed when glucose chemically combine with haemoglobin molecule. This study examined glycosylated haemoglobin as a possible surrogate marker for dyslipidemia and glycemic index in type 2 diabetes mellitus subjects. A cross- sectional study was carried out in Warri, Delta State with a total of four hundred (400) volunteers recruited comprising of three hundred and twenty (320) diabetes mellitus subjects and eighty (80) apparently healthy subjects. Standard methods were used for anthropometric measurement and biochemical assays. Data were analyzed using statistical package for social sciences (SPSS). Parameters including Blood pressure, body mass index, fasting blood glucose, glycosylated haemoglobin, total cholesterol, triglycerides, LDL-C were significantly higher in diabetic subjects than non- diabetics while HDL-C was significantly lower in diabetics. Glycosylated haemoglobin is positively correlated with blood glucose, cholesterol, triglycerides, and LDL-C but inversely associated with HDL-C. Based on this study, glycosylated haemoglobin has the potential to serve as surrogate marker of dyslipidemia.

Effect of Magnetite Nanoparticles on Human Blood Components.

The qualitative composition and zeta potential of magnetite nanoparticles (size 4.2±1.2 nm) obtained by co-precipitation method were determined by X-ray and diffraction dynamic light scattering. The zeta potential of Fe3O4 particles was -15.1±4.5 mV. The possibility of interaction of magnetite nanoparticles with human blood plasma proteins and hemoglobin as well as with erythrocyte membranes was demonstrated by spectrophotometry, electrophoresis, and fluorescence methods. No changes in the sizes of hemoglobin molecules and plasma proteins after their modification by Fe3O4 particles were detected. The possibility of modifying the structural state of erythrocyte membranes in the presence of magnetite nanoparticles was demonstrated by means of fluorescent probe 1-anilinonaphthalene-8-sulfonate.

Structural and functional features of donor blood hemoglobin in the presence of doxycycline and mexidol

The effect of mexidol, doxycycline hydrochloride and sodium nitrite solutions on human oxyhemoglobin molecules was studied by spectrophotometry. It is shown that the presence of modifiers in the incubation medium in combination and separately contributes to their specific affinity to the hemoglobin molecule, which is reflected in the change in the ratio of ligand forms of hemoprotein. A tendency to decrease the level of methemoglobin formation in samples containing doxycycline and mexidol was revealed. Preliminary incubation of hemoglobin solutions with antibiotics studied helps to reduce the oxidative effect of sodium nitrite against hemoprotein molecules. The data obtained confirm the concept of the presence of non-antibacterial effects of doxycycline.

The impact of mutual interactions between ZIFs-MWCNTs and hemoglobin molecule on electrocatalysis on hydrogen peroxide reduction of integrated heme protein

The impact of mutual interactions between ZIFs-MWCNTs and hemoglobin molecule on electrocatalysis on hydrogen peroxide reduction of integrated heme protein

Metabolic regulation of erythrocyte development and disorders

The formation of new red blood cells (RBC) (erythropoiesis) has served as a paradigm for understanding cellular differentiation and developmental control of gene expression. The metabolic regulation of this complex, coordinated process remains poorly understood. Each step of erythropoiesis, including lineage specification of hematopoietic stem cells, proliferation, differentiation, and terminal maturation into highly specialized oxygen-carrying cells, has unique metabolic requirements. Developing erythrocytes in mammals are also characterized by unique metabolic events such as loss of mitochondria with switch to glycolysis, ejection of nucleus and organelles, high-level heme and hemoglobin synthesis, and antioxidant requirement to protect hemoglobin molecules. Genetic defects in metabolic enzymes, including pyruvate kinase and glucose-6-phosphate dehydrogenase, cause common erythrocyte disorders, whereas other inherited disorders such as sickle cell disease and β-thalassemia display metabolic abnormalities associated with disease pathophysiology. Here we describe recent discoveries on the metabolic control of RBC formation and function, highlight emerging concepts in understanding the erythroid metabolome, and discuss potential therapeutic benefits of targeting metabolism for RBC disorders.

High-Oxygen-Affinity Hemoglobins-Case Series and Review of the Literature.

Modifications of the hemoglobin (Hb) structure in regions involving the regulation of oxygen transport may lead to an increased oxygen affinity for the hemoglobin molecule and impaired oxygen delivery to the tissues. Herein, we present six patients with high-oxygen-affinity Hb variants, either in heterozygous form or in compound heterozygosity (such as heterozygosity for Hb Hiroshima, Köln, Crete, and compound heterozygosity Hb Crete with β or δβ thalassemia), in order to demonstrate the need for prompt and accurate diagnosis and enrich the limited literature due to the rarity of such cases. Hb Crete, Hb Hiroshima, and Hb Köln have distinct pathophysiologies and may result in different clinical phenotypes. In conclusion, high-oxygen-affinity hemoglobins are rare and inherited within a dominant autosomal manner, have various clinical presentations, and should always be suspected in patients with erythrocytosis. Their management (as phlebotomy or low-dose aspirin) should be based on an individualized assessment of the risk of complications, the medical history, concomitant symptoms, and quality of life.