Hemoglobin Chains Research Articles

Prevalence and distribution of major β-thalassemia mutations and HbE/β-thalassemia variant in Nepalese ethnic groups

BackgroundBeta-thalassemia is a genetic disorder that is inherited in an autosomal recessive pattern. This genetic disease leads to a defective beta-globin hemoglobin chain causing partial or complete beta-globin chain synthesis loss. Beta-thalassemia major patients need a continuous blood transfusion and iron chelation to maintain the normal homeostasis of red blood cells (RBCs) and other systems in the body. Patients also require treatment procedures that are costly and tedious, resulting in a serious health burden for developing nations such as Nepal. MethodsA total of 61 individuals clinically diagnosed to have thalassemia were genotyped with multiplex amplification refractory mutation system–polymerase chain reaction (ARMS–PCR). Twenty-one major mutations were investigated using allele-specific primers grouped into six different panels. ResultsThe most common mutations found (23%) were IVS 1–5 (G-C) and Cd 26 (G-A) (HbE), followed by 619 deletion, Cd 8/9 (+G), Cd 16 (–C), Cd 41/42 (–TTCT), IVS 1–1 (G–T), Cd 19 (A-G), and Cd 17 (A-T) at 20%, 12%, 8%, 6%, 4%, 3%, and 1%, respectively. ConclusionThe results of this study revealed that Nepal's mutational profile is comparable to that of its neighboring countries, such as India and Myanmar. This study also showed that thalassemia could be detected across 17 Nepal's ethnic groups, especially those whose ancestors originated from India and Central Asia.

Ocular abnormalities in patients with beta-thalassemia: a prospective study

<p><strong>Background: </strong>Beta thalassemia is severe genetic blood disorder caused by mutation in the gene encoding for the beta chains of haemoglobin and individuals with beta thalassemia require life-long red blood cell transfusions to survive which leads to hemosiderosis and affects all the organs in the body including eyes. The study aims to study ocular manifestations in these children and its correlation with age and serum ferritin levels.</p><p><strong>Methods: </strong>A descriptive cross-sectional study was done in government medical college Jammu in 2014-2015 on 67 BTM children. Children below 3 years of age and with pre-existing ocular abnormalities, infections were excluded from the study. Ocular examination was done for any major eye abnormality, congenital malformations or trauma. Retinal examination was done using direct and indirect ophthalmoscope, changes were recorded.</p><p><strong>Results: </strong>47.76% of children belonging to the group: 5-10 years, while only 5.97%, i.e., 4 in number pertained to the age group: >15 years. Lens opacity was seen in 29.85% of children. 31 children showed changes in retinal activity, while decreased visual acuity was also observed in 17 children. Iris was significantly affected in children with serum ferritin >2500 ng/ml. Even greater lenticular changes and opacities were observed in children with higher serum ferritin levels (>4500 ng/ml).</p><p><strong>Conclusions: </strong>As life expectancy for beta-thalassemia patients extends, regular monitoring of the progression of disease and symptoms to detect early changes in their ocular system is recommended, to achieve a better quality of life for this patient group.</p>

In silico analysis of missense Single Nucleotide Variants (SNVs) in HBB gene associated with the β-thalassemia

Backgroundβ-Thalassemia is a rapidly prevailing autosomal recessive disorder throughout the world. The human beta-globin gene (HBB) is responsible for the synthesis of the β-globin chains of hemoglobin, and numerous mutations in this gene, are correlated with the β-thalassemia. Among these mutations, Single Nucleotide Variations (SNVs) are the primary genetic factors behind the etiology of β-thalassemia. ObjectiveThis study aims to identify the pathogenic missense mutations from the conserved regions of β-globin, decreasing protein stability and altering molecular interactions and three-dimensional folding of the mutated proteins. The nominated mutations would, therefore, more likely to associate with the incidence of this disease. MethodsComputational tools based on sequence homology (SIFT, PROVEAN, PANTHER & Mutation Assessor), supervised learning (SNAP2, PhD-SNP, SNP&GO, SuSpect & MutPred), and consensus-based algorithms (PredictSNP & PON-P2) pinpoints the potentially pathogenic missense variants from the HBB gene. Furthermore, the ConSurf tool screens mutations, specifically from the evolutionarily conserved regions of the protein. Finally, the mutations decreasing protein stability were compared with the native proteins' model to highlight the differences in 3D structure, molecular interactions, and protein folding. ResultsA total of 12 pathogenic missense mutations including, G25V, G25D, G25R, G65D, T39P, P37H, P37T, H93P, H93D, L97P, D100V, and P101R, are recognized from the beta-globin protein. These mutations were disturbing the molecular interactions of mutated proteins, decreasing the stability of this protein. ConclusionsThe identified mutations could be the potential genetic aberrations responsible for the beta-thalassemia, all these mutations, however, need experimental validations before their use for the screening and management of the β-thalassemia.

Genetic Polymorphism of Endothelial Nitric Oxide Synthase in Sickle Cell Disease Patients in South-Eastern Nigeria

Background: Sickle cell disease (SCD) is an inherited blood disorder resulting from a point mutation of thymine (T) for adenine (A) at codon 6 of the gene for beta-globin chain of haemoglobin, leading to substitution of Valine for Glutamate at position 6 of the amino acid sequence, thereby shifting the isoelectric point of the protein. The single nucleotide polymorphism (SNP) (T-786C) in the 5’ promoter region which affects the expression of endothelial nitric oxide synthase (ENOS) gene is critical in determining the predisposition of humans to diseases including SCD. This work was therefore aimed at investigating the presence of SNP (T-786C) in the 5’ promoter region of ENOS gene in patients with SCD with respect to controls, visiting the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State, south-Eastern Nigeria. Materials and Methods: The study recruited a total of 50 subjects including 20 SCD patients (SS), 15 sickle cell carriers (AS) and 15 healthy non-carriers (AA). DNA was extracted from venous blood samples; PCR amplification was done using specified primers to the region of polymorphism, and finally followed by HpaII restriction enzyme digestion. Results: The results obtained showed only TT genotype across all samples, and so could not establish any relationship between the SNP T-786C ENOS gene region and SCD. There was presence of the same genotype in both test and control groups. Conclusion: This research findings therefore suggest that T-786C ENOS gene polymorphism is not associated with SCD in south-Eastern Nigeria and thus cannot genetically influence the phenotypic outcome of the disease in the clime.

Osteomyelitis in Children with Sickle Cell Disease: A Challenging Diagnosis: Case Report from Cameroon

Introduction: Sickle Cell Disease (SCD) is the most prevalent genetic disease in the world predominantly in the African population with Sickle Cell Anaemia (SCA) being its dominant form. One of the most frequent complications of SCD is osteomyelitis. SCA is due to a point mutation in the beta globin chain of haemoglobin. This is responsible for the sickled shape of RBCs under low oxygen tension conditions leading to obstruction in the microcirculation. This leads to vaso-occlusive crises (VOC) which has a similar clinical presentation to that of osteomyelitis, another complication of SCD. Case Presentation: We present the case of a three-year-old girl with SCA who presented with an inability to bear weight in a febrile context. A diagnosis of VOC was initially made, which was later on changed to both a left chronic tibial and right distal femoral osteomyelitis following a series of biological, and imaging investigations. Surgical debridement and drainage were performed, resulting 9 weeks later in the involution of fever and leg pain. Conclusion: Osteomyelitis when associated with SCD is a dreadful and deathly disease in low income countries as it also presents like VOC therefore higher suspicion index is recommended. It is therefore important to take this into consideration at an early stage in patients with homozygous sickle cell disease so as to rapidly initiate multidisciplinary care. Appropriate investigations, appropriate antibiotic therapy, and timely surgical intervention would help to greatly reduce morbidity and mortality.

Bioinformatic Analysis of Insertion, Deletion, and Substitution Mutations in the Human <i>β</i>-Globin Gene

Beta-thalassemia is delineated as a bunch of heritable blood disorders characterized by abnormalities within the synthesis of beta chains of hemoglobin. Most defects in hemoglobin arise directly from mutations in the structure of the β-globin sequence (HBB). Recent advances in computational tools have made it possible to study the relationship between genotype and phenotype in many diseases, including β-thalassemia. Due to the high prevalence of β-thalassemia, these analyses have helped to know the molecular basis in a better way. In this direction, a related database, called HbVar, was developed in 2001 by a collective academic effort to provide quality and up-to-date information on genomic variations that lead to hemoglobinopathies and thalassemia. Within present study, the aim was to investigate insertion, substitution, and deletion mutations in HBB collected from HbVar and their effects using the in-silico approach. In this comparative analysis, three sequences, one wild-type and two mutated HBB sequences were studied in the South American region. It was determined that the Brazilian nd-HPFH mutated sequence presents the formation of a beta chain in the protein structure, not being able to align or overlap in the wild-type, which results in the alteration of the function of the protein, and therefore the development of Thalassemia disease.

It is Time to Revise the Ventilation Strategy in COVID-19 Affected Patients

COVID-19 infection has emerged as a pandemic. This infection is new to the world, and the management strategy is evolving daily. As per the current guidelines, the patients of COVID-19 infection requiring mechanical ventilation should be treated on the lines of management of Acute Respiratory Distress Syndrome (ARDS). However, it seems that the management of ventilation in the case of COVID-19 needs to be modified. With growing experience, many hospitals have turned to Non-Invasive Ventilation (NIV) to ward-off severe respiratory failure and in keeping with the inadequate resources. The controversy in using NIV is whether the benefits of using such interventions are more than the potential risks of aerosolisation of the virus. There is a hope that helmet-based ventilation may help reduce the risk of nosocomial infection. Autopsy findings demonstrated that besides ARDS, the alveolar capillaries were clearly thickened, with fibrin thrombi within the capillaries and small vessels and surrounding oedema present in COVID-19 affected lungs. This virus attacks the beta chain of haemoglobin, dissociates heme, removing iron converting it to porphyrin. The cause of desaturation is the failure of the blood to carry oxygen leading to multiorgan failure and mortality. The cause of lung damage seen on Computerised Tomography (CT) scans is the release of oxidative iron, which in turn overcomes the natural defenses against pulmonary oxidative stress and causes what is known as the Cytokine Storm. The question is whether mechanical ventilation is harming the patient by traumatising their lungs leading to increased mortality. Prone ventilation is the next preferred step for COVID-19 patients who fail to achieve adequate oxygenation with low tidal volume ventilation. Hyperbaric oxygen therapy can help the leftover functioning haemoglobin to carry more oxygen. Blood transfusion and plasmapheresis provide symptomatic relief. Thrombolytic therapy is also being tried with some benefits. These may be promising in treating patients with COVID-19 infection. Researches are required on the other probability and to test newly emerging treatment modalities.

Role of Complement Regulatory Proteins (CD55, CD59, and CD35) on Red Blood Cells of <i>β</i>-Thalassaemia Patients

Background: β-thalassaemia (β-Thal) is an inherited chronic haemolytic anaemia resulting from absent or low level of synthesis of β-globin chains of haemoglobin A in erythropoietic cells. The complement system is an important part of innate immune response that may be implicated in red blood cell (RBC) lysis. Mammalian cells are provided with surface bound complement regulatory proteins (MCRPs) that regulate the activation of complement cascade, thus protecting them from uncontrolled complement-mediated lysis. Objective is to evaluate the role of complement regulatory proteins (CD55, CD59, and CD35) on red blood cells, and to explain the pathogenesis of anaemia in β-thalassemia major. Methods: This case-control study enrolled 74 β thalassemia major patients who were compared with 40 age and sex matched controls. We performed expression of CD55, CD59, and CD35 on RBCs using flow cytometry. Results: CD55 levels of β-thalassemia major patients (79.78% ± 18.54%) were significantly decreased compared to healthy controls (99.45% ± 0.59%) (P β-thalassemia major patients (97.76% ± 1.72%) were significantly lower than in the controls (99.75% ± 0.36%) (P β-thalassemia major patients (4.30% ± 4.66%) than in the control group (19.40% ± 10.90%) (P Conclusion: β-thalassemia major patients suffer from increased haemolysis and a consequent increase in their demand for blood transfusion. Complement-mediated haemolysis was shown in our study by decreased expression of CD55, CD59, and CD35 in β-thalassemia major patients. This allows complement deposition on RBCs and enhances or accelerates their lysis.

PENGARUH PEMBERIAN JUS BUAH NAGA TERHADAP PERUBAHAN KADAR PROFIL DARAH IBU HAMIL DENGAN ANEMIA YANG MENDAPATKAN SUPLEMENTASI TABLET FE

Anemia is a reduced number of red blood cells or hemoglobin content in the blood. The largest group that can experience anemia are pregnant women. Causes of anemia in pregnant women include the production of hemoglobin chains due to certain diseases or experiencing impaired hemoglobin production due to a lack of iron, folic acid or vitamin B12. Existing research states that dragon fruit can overcome anemia, where dragon fruit contains substances that the body needs for the formation and maturation of blood cells. The research objective was to determine the effect of dragon fruit juice on changes in blood profile levels in pregnant women with anemia who received iron supplementation. The research method used was a quasi-experimental design with a nonrandomized pretest and posttest design with control group design. This research was conducted for 7 weeks. The number of samples in this study were 40 respondents (20 respondents in the intervention group who received dragon fruit juice and Fe tablet supplementation and 20 respondents who only received iron tablet supplementation). Samples were obtained using purposive sampling. Evaluation of blood profile levels was carried out after giving dragon fruit juice on day 15. The results showed an increase in hemoglobin, hematocrit, and erythrocyte levels (p = 0,000), meaning that giving dragon fruit juice to pregnant women with anemia had an effect on increasing hemoglobin levels. hematocrit, and erythrocytes. For health services, it is hoped that dragon fruit juice can be used as an alternative in overcoming anemia in pregnant for women.

Frequencies of Abnormal Haemoglobin Electrophoretic Patterns in Hemolytic Anemia cases in District Swat.

Background: Thalassemia is a genetic disorder due to deletion or mutation in the gene for alpha or beta chain of hemoglobin. Thalassemia, sickle cell disease, HbD, HbE, HbC and other such disorders are genetic defects associated with hemolytic anemia's and other complications. The prevalence of these are significantly growing in Pakistan especially in the northern areas of Pakistan. Its prompt detection is of paramount importance, both for the prevention of thalassemia major and clinically severe other hemoglobinopathies as well as for the epidemiological purposes.Objective: To assess the frequencies of abnormal hemoglobin variants in the suspected cases of hemolytic anemia's, in the population of district swat. Material and Methods: A total of 1832 suspected cases of hemolytic anemias admitted in SGTH/SMC were assessed after taking clinical and familial history. Whole blood samples were collected in EDTA tube; complete blood counts with peripheral smears were prepared. All samples were processed with fully automatic micro capillary hemoglobin electrophoretic movability (SEBEA micro capillary electrophoresis).Results: A normal Hb pattern was observed in 1224 (66.81%) cases and abnormalities were detected in 608 (33.18%) cases. â (beta) thalassemia trait was the commonest abnormality found in 477 (26.03 %) patients followed by â thalassemia major 53 (2.89 %), â thalassemia intermedia 24 (1.31 %), raised HbF for age review after one year 17 (0.92 %), Sickle cell trait 9 (0.49 %), Sickle cell disease 8 (0.43 %), sickle/beta-thalassemia 6 (0.32 %) HbD Trait 5 (0.27 %), HbE (0.21%) and HbC (0.10%) were common hemoglobinopathies.Conclusion: Amongst hemoglobinopathies, â- (beta) thalassemia and sick cell trait/disease is the most common of the hemoglobinopathies in the study area.

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, endocannabinoids also bind to other groups of receptors. Furthermore, another group of lipids are considered to be endocannabinoids, such as the fatty acid ethanolamides, the fatty acid primary amides and the monoacylglycerol related molecules. Recently, it has been shown that the hemopressin peptide family, derived from α and β chains of hemoglobins, is a new family of cannabinoids. Some studies indicate that hemopressin peptides are expressed in the central nervous system and peripheral tissues and act as ligands of these receptors, thus suggesting that they play a physiological role. In this review, we examine new evidence on lipid endocannabinoids, cannabinoid receptors and the modulation of their signaling pathways. We focus our discussion on the current knowledge of the pharmacological effects, the biosynthesis of the peptide cannabinoids and the new insights on the activation and modulation of cannabinoid receptors by these peptides. The novel peptide compounds derived from hemoglobin chains and their non-classical activation of cannabinoid receptors are only starting to be uncovered. It will be exciting to follow the ensuing discoveries, not only in reference to what is already known of the classical lipid endocannabinoids revealing more complex aspects of endocannabinoid system, but also as to its possibilities as a future therapeutic tool.

Activin Receptor-Ligand Trap for the Treatment of β-thalassemia: A Serendipitous Discovery.

β-thalassemia is a hereditary disorder caused by defective production of β-globin chains of hemoglobin (Hb) that leads to an increased α/β globins ratio with subsequent free α-globins. Alpha globin excess causes oxidative stress, red blood cells membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis.The transforming growth factor β (TGF-β) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and plays an essential role in regulating the hematopoiesis. This pathway can lose its physiologic regulation in pathologic conditions, leading to anemia and ineffective erythropoiesis. Activin receptor-ligand trap molecules such as Sotatercept and Luspatercept downregulate the TGF-β pathway, thus inhibiting the Smad2/3 cascade and alleviating anemia in patients with β-thalassemia and myelodysplastic syndromes.In this review, we describe in extenso the TGF-β pathway, as well as the molecular and biological basis of activin receptors ligand traps, focusing on their role in various β-thalassemia experimental models. The most recent results from clinical trials on sotatercept and luspatercept will also be reviewed.

Association between Hepatic Enzymes Levels and Persistent Hepatomegaly in Sickle Cell Patients

Background Sickle cell disease is one of group of blood disorders and diseases that affect red blood cells. Like other haemoglobinopathies, sickle cell disease is inherited single-gene disorders inherited as autosomal co-dominant traits characterized by a single point mutation in the ?-chain of human haemoglobin leading to life-long illness. The severity of the disease varies widely from person to person essentially due to resultant multi-organ failure including liver dysfunction, which can be multifactorial. Broad Objective This study, was carried out to determine the association and potential role hepatic enzymes as biochemical indices may have on the severity of sickle cell anaemia diseases. Methods This was cross-sectional study that was done at sickle cell clinic at Muhimbili National Hospital in Dar es Salaam, Tanzania using an English checklist as a main research tool with a sample size of 75 eligible sickle cell patients. All sickle cell patients who had been attending clinic from September 2016 to October 2016 and had hepatic enzymes test being done were included in the study. Categorical variables were compared using Chi-Square (c2) and binary variables tested using Cochran–Mantel–Haenszel test with p-values <0.05 considered statistically significant. The main findings show that, there was significant association between hepatomegally and liver function tests in patients with sickle cell disease. The association between hepatomegaly and abnormalities in all liver function tests, including alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, albumin and total protein levels was statistically significant (p < 0.05). The Cochran–Mantel–Haenszel test (CMH) for binary categorical variables as well as the association between liver function tests abnormalities and hepatomegaly had exact match (p = 0.05). Conclusion This study found association between abnormalities in liver function tests and hepatomegaly in sickle cell patients to advocate regular screening as an urgent remedy to prevent adverse lethal complications in African setting. Key Words: Hepatic Enzymes, Hepatomegaly, Sickle Cell Disease.

Biochemical and molecular analysis of the beta-globin gene and LCR region on Saudi β-thalassemia patients.

IntroductionBeta-thalassemias are a group of inherited blood disorders caused by reduced or absent synthesis of beta chain of hemoglobin resulting in variable phenotypes ranging from clinically asymptomatic individuals to severe anemia symptoms. The objective of this study is to screen for the whole beta gene globulin and the LCR region and its clinical relevance in β-Thalassemia patients.MethodsIn this study, we collected 140 blood patients' samples with beta-thalassemia from different areas of Saudi Arabia. DNA was then extracted then the molecular scanning for the whole β-globin gene and the Locus control region (β-LCR) for patients' samples, was run using PCR.ResultsSixty one mutations found in this study, including 22 new mutations not recorded in the database before. These deletions including: (*C-1960-1961 ca/-- del in hbb5) and (*c-519C<T homo, *c-390C<T homo in hbb6) were the highest among beta-thalassemia in the study, which indicates a strong sign of injury associated with the disease. Meanwhile, There are other mutations found most common among patients and was linked with the severity of clinical symptoms including: (c-1960-1961 ca/-- del in hbb5), (c-519C<T homo, c-390C<T homo, c-160 G<A het in hbb6), (c.315+282 G<A het, c.316-225G<A het, c.315+342 G > A het in hbb9). Interestingly, the highest percentage in gene deletion occurred in exon 03A by ∼33% of the samples, while the highest percentage in gene addition of the gene occurred in exon 03B by ∼25%.ConclusionThis study was unique to show several new mutations that would help in diagnosis and treatment. These results should be taken further to set up better management strategies to improve outcomes.

Neurological Deficits among Beta-Thalassemia Patients and its Possible Therapeutic Intervention : A Comprehensive Review

Beta-thalassemia is a genetico-haematological disorder that affects the integrity, structure, and survival of red blood cells due to deleterious mutation in the β-globulin chain of hemoglobin. Other than blood disorder, this condition gives rise to numerous neurological and haematophysiological conditions which have not been fully discussed yet. These conditions include extramedullary hematopoiesis, evoked potential (Sensory, Auditory and Visual), neuropathy and myopathy and predisposition to the hypercoagulable state leading to stroke. Moreover, most opted therapy to alleviate this condition intrigue neurotoxicity that requires clinician's round the clock attention. Beta thalassemia remains an incurable disease, and various therapies have been introduced to fulfill the body's blood requirement. But this condition implicitly gives rise to a damaging range of symptoms that cannot be overlooked. Therefore, our review encompasses all those anomalies associated with beta-thalassemia and its probable curative therapy. Keywords: Beta thalassemia, Neurological deficits, Cognitive impairment, Extramedullary hematopoiesis, Evoked potential, Neuropathy.

Phenotypical and functional abnormalities of circulating neutrophils in patients with β-thalassemia.

β-Thalassemia is an inherited single gene disorder related to reduced synthesis of the β-globin chain of hemoglobin. Patients with β-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in β-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in β-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with β-thalassemia major and with β-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of β-thalassemia.

A glycomics and proteomics study of aging and Parkinson\u2019s disease in human brain

Previous studies on Parkinson’s disease mechanisms have shown dysregulated extracellular transport of α-synuclein and growth factors in the extracellular space. In the human brain these consist of perineuronal nets, interstitial matrices, and basement membranes, each composed of a set of collagens, non-collagenous glycoproteins, proteoglycans, and hyaluronan. The manner by which amyloidogenic proteins spread extracellularly, become seeded, oligomerize, and are taken up by cells, depends on intricate interactions with extracellular matrix molecules. We sought to assess the alterations to structure of glycosaminoglycans and proteins that occur in PD brain relative to controls of similar age. We found that PD differs markedly from normal brain in upregulation of extracellular matrix structural components including collagens, proteoglycans and glycosaminoglycan binding molecules. We also observed that levels of hemoglobin chains, possibly related to defects in iron metabolism, were enriched in PD brains. These findings shed important new light on disease processes that occur in association with PD.

PARATHYROID HORMONE AND BIOCHEMICAL METABOLIC BONE MARKERS IN PATIENTS WITH β-THALASSEMIA MAJOR IN MISAN PROVINCE / IRAQ

Beta-thalassemia is a heterogeneous group of hereditary blood disorders characterized by defects in the synthesis of the β- chains of hemoglobin, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. This study aims to assess the serum PTH, vitamin D, calcium, phosphorus, alkaline phosphatase, and magnesium levels in β-thalassemia major patients. A total of 50 (30 male and 20 female) patients with β- thalassemia major with ages range 11- 16 years and an equal number of sex-matched healthy adolescents as a control group were included in this study. A total of 52% of patients were lived in an urban area, and there was no significant difference between patients and the control group regarding residency. Male patients showed low statistically significant (P 0.05) mean serum PTH, vitamin D, and calcium levels, but mean serum phosphorus and alkaline phosphatase levels were significantly higher (P 0.05) as compared to the male control group. However, female patients had low, but without statistical significant (P&gt;0.05) mean serum PTH level, whereas vitamin D and calcium levels were highly significant (P 0.05) reduced. The phosphorus and ALP levels were highly significantly (P 0.05) increased as compared to female controls. Regarding β- thalassemia major group, the current study showed male patients had non-significant (P 0.05) higher levels of PTH, calcium, phosphorus, and ALP. In contrast, vitamin D level was non-significantly (P 0.05) low in male patients as compared to female patients. Mean serum level of PTH had a negative correlation with phosphorus, but it had a positive association with vitamin D, calcium, ALP, and magnesium. In conclusion, this study demonstrated that β-thalassemia major patients have a markedly deranged biochemical metabolic bone profile. Regular monitoring of PTH and biochemical mineral profile is also recommended.

Impact of SARS CoV-2 in Hemoglobinopathies with Immune Disfunction and Epidemiology. A Protective Mechanism from Beta Chain Hemoglobin Defects?

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Gene Therapy: The New Weapon Against Diseases Until there Difficult to Overcome, Some Current Facts of Gene Therapy and Cases of Sickle Cell Anemia

Sickle cell anemia is an inherited genetic disease that affects the hemoglobin chains of red blood cell hemoglobin, carrying oxygen-less well through the body. It is a rare disease; however, it is the most widespread genetic disease in the world and especially widespread in sub-Saharan Africa. It causes anemia, painful seizures that affect several organs; it is also called sickle cell anemia, this disease results in a deformation of red blood cells in the form of sickle or a crescent moon, which prevents normal circulation in the blood vessels.