Hemoglobin Chains Research Articles

Multiscale MD simulations of wild-type and sickle hemoglobin aggregation.

Sickle cell disease is a hemoglobinopathy resulting from a point mutation from glutamate to valine at position six of the β-globin chains of hemoglobin. This mutation gives rise to pathological aggregation of the sickle hemoglobin and, as a result, impaired oxygen binding, misshapen and short-lived erythrocytes, and anemia. We aim to understand the structural effects caused by the single Glu6Val mutation leading to protein aggregation. To this end, we perform multiscale molecular dynamics simulations employing atomistic and coarse-grained models of both wild-type and sickle hemoglobin. We analyze the dynamics of hemoglobin monomers and dimers, study the aggregation of wild-type and sickle hemoglobin into decamers, and analyze the protein-protein interactions in the resulting aggregates. We find that the aggregation of sickle hemoglobin is driven by both hydrophobic and electrostatic protein-protein interactions involving the mutation site and surrounding residues, leading to an extended interaction area and thus stable aggregates. The wild-type protein can also self-assemble, which, however, results from isolated interprotein salt bridges that do not yield stable aggregates. This knowledge can be exploited for the development of sickle hemoglobin-aggregation inhibitors.

MO795: Management of Anemia in Hemodialysis Patients With Thalassaemia Minor

Abstract BACKGROUND AND AIMS Thalassemia is a group of hemoglobinopathies characterized by the decrease or lack of β or α globin chain production (Hb) [1]. Minor thalassemia has little to no symptoms since the other gene is capable of compensating for the anomaly; however, it represents a rare cause of resistance to erythropoietin (EPO) in chronic hemodialysis patients (CHP) in multiple regions, particularly the Mediterranean region [2]. As a matter of fact, CHP suffering from minor thalassemia often take higher EPO doses to correct the anemia [3], even if all causes of EPO resistance are resolved; a recent Italian investigation indicated that EPO need in this population is almost double in comparison with other groups [4]. EPO résistance can be secondary to the quantitative anomalies of the hemoglobin chain, notably Hb A2 and Hb F, Biagio Di Lorio et al. reported a positive correlation between the percentage of Hb A2 and EPO doses [5], actually patients that had an Hb A2 >6% needed higher EPO doses and vice versa. The aims of this study were to evaluate the efficiency of different therapeutic means [Erythropoiesis-stimulating agents (ESA), blood transfusion (TS)] aiming to correct the anemia in CHP with minor thalassemia. To detect the correlation between quantitative anomalies in hemoglobin chains and EPO resistance. METHOD It's a descriptive multi-centric study, involves eight CHP suffering from minor thalassemia. The statistical analysis of the data was done through Excel using the correlation coefficient and SPSS using the P-value. A value <.05 was considered as significant. RESULTS The average value of hemoglobin was 7.35 g/dL, Ferritin (M: 964 ± 971 ng/L) and PTH levels (M: 433 ± 126 pg/mL). These results are detailed in Table 1. Electrophoresis was done for all our patients with an average of HbA à 96.2 ± 1.7%; HbA2 à 3.43 ± 1.41%; HbF à 0.35 ± 0.45%. We have noticed that a decreased percentage up to nul of Hb F fraction is correlated with the lowest Hb levels (Fig. 1). The main therapeutic mean in anemia patients is epoietin beta, the average dose given to patients is 300 UI/kg/week, 326UI/kg/s at 2 months, 233 UI/kg/s at 6 months and 326 UI/kg/s at 12 months. Figure 2 illustrates the response to the EPO during the maintenance phase. The Darbepoetin alpha (μg/Kg/s) is administered (depending on availability) to two patients out of the eight. One of the two was receiving a dose of 0.57 μg/kg/s for 8 weeks, the other one was receiving a dose 0.7 μg/kg/s for 8 weeks as well, with a different response in the two patients. CONCLUSION: The presence of minor thalassemia in chronic hemodialysis patients entails erythropoietin resistance and a serious case of anemia. In our study, the maximum EPO dose used was 500 UI/kg/s reaching a value of 9.7 g/dL of Hb.

The Correlation Results of Examination of Hemoglobin and The Erythrocyte Index in Patients With Suspected Covid-19 in The Hospital of Kendari City

Coronavirus disease 2019 has become a global problem causing hundreds of thousands of deaths worldwide. Haemoglobin is more susceptible to COVID-19 virus attacks. Haemoglobin functions as a carrier of oxygen to organs in the body. When the concentration of haemoglobin in the blood circulation is low, the transport of oxygen to several organs in the body can be disrupted. SARS-CoV-2 interacts with haemoglobin in red blood cells. This interaction causes the virus to break the haemoglobin chain and cause hemolysis. The erythrocyte index which consists of MCV, MCH, and MCHC values ​​is used to indicate the occurrence of anemia in COVID-19 patients. This research method used descriptive analytic with a cross sectional study design. The population of this study was suspected COVID-19 patients with a sample of 27 people. Sampling was carried out using purposive sampling. This study aims to determine the relationship between haemoglobin examination results and erythrocyte index in suspected COVID-19 patients.The instrument in this study used secondary data which included the results of examination of haemoglobin values ​​and erythrocyte index. The results of the test using a parametric statistical approach with the correlation analysis method showed that there was a correlation between the results of the haemoglobin and MCV test (P-value 0.057 > 0.05), while the haemoglobin and MCH test had no correlation (P value 0.777 > 0.05), and there is no correlation between haemoglobin and MCHC examination (P-value 0.372 > 0.05).

Prevalence of transfusion-transmitted infections in multiple blood transfusion-dependent thalassemic patients in Asia: A systemic review.

BackgroundThalassemia is a hereditary hemolytic anemia marked by a defect in synthesizing one or more globin chains in hemoglobin. In Pakistan, approximately 10,000 patients with thalassemia are primarily dependent on blood transfusions. The β-thalassemia patients require blood transfusions and iron chelation therapy. Patients who need blood transfusions are at an increased risk of contracting transfusion-transmitted infections (TTIs) such as hepatitis B and C viruses (HBV and HCV, respectively), as well as the human immunodeficiency virus (HIV).ObjectiveThis systemic review aims to assess the prevalence of TTIs in transfusion-dependent β-thalassemia patients in Asia.MethodsThe data for the systematic review were gathered from PubMed, Google Scholar, the Directory of Open Access Journals (DOAJ), and ScienceDirect using the following keywords: “prevalence, HBV, HCV, HIV, thalassemia, and transfusion-transmitted infections (TTIs)," and so on. This review includes the research articles that address the prevalence of viral infections in thalassemic patients following blood transfusion.ResultsA preliminary search of various databases identified 231 potential studies. 157 duplicate studies were eliminated, and the eligibility of 59 full-length articles was determined. Only 43 studies met the inclusion criteria. Among the 43 studies analyzed, 11 reported a high prevalence of HCV alone in thalassemic patients, while 21 reported a high prevalence of HCV and HBV infection in thalassemic patients. Eight studies reported the prevalence of all three TTIs examined, namely, HCV, HBV, and HIV, in patients with transfusion-dependent thalassemia.ConclusionPreventable transfusion-transmitted infections occur frequently, and robust national policies and hemovigilance are required to detect and mitigate the infection risk.

Elastic property of sickle and normal hemoglobin protein: Molecular dynamics

This work focuses on identifying the conformational stability and binding components in sickle and normal hemoglobin to explore the elastic properties and realize the stiffness by using molecular dynamics simulation. Our investigation shows that a larger force is required to separate the beta chain of normal hemoglobin in comparison to the sickle hemoglobin by using steered molecular dynamic. In sickle hemoglobin protein (HbS), the hydrogen bond binding force of the beta chain is 7073.74–12 646.80 pN for pulling velocities of 0.000 20–0.000 40 nm/ps with the spring constant of 800 kcal mol−1 nm−2. Similarly, in normal hemoglobin protein, the hydrogen bond binding force in the beta chain ranges from 12 005.00 to 17 753.70 pN for the same values of pulling velocities and spring constant. This indicates that the normal hemoglobin is stiffer than sickle hemoglobin. We have also analyzed the solvent accessible surface area (SASA) of both proteins, and our investigation shows that the SASA of normal hemoglobin is much less than that of sickle hemoglobin because of the sickled structure of HbS. We have also studied the van der Waals (vdW), electrostatic, hydrophobic, and salt bridge interactions in both kinds of hemoglobin. The sum of vdW, electrostatics, and hydrophobic interactions in HbS is higher, whereas salt bridge interactions are found lower in sickle normal hemoglobin proteins than in normal hemoglobin protein.

EPIDEMIOLOGY OF DOWN’S SYNDROME & Β- THALASSEMIA IN INDIA

Down’s syndrome and Beta (β) Thalassemia are commonly prevalent genetic diseases worldwide. Down’s syndrome is predominantly caused by an extra copy of chromosome 21 or trisomy 21. Maternal age above 35 years significantly increases the chances of a Down’s syndrome birth. In India, there are approximately 21,000 Down’s syndrome births every year. β-Thalassemia is a blood disorder caused by abnormal synthesis of the β chains of hemoglobin. India has over 35-45 million carriers of this disease. This is a survey-based study, which aims to understand the epidemiology of Down’s syndrome and Beta Thalassemia in the Indian population. This online survey was answered by 297 Indian or Indian origin adults. Both females and males were the respondents. Results of the study indicated that prevalence of Down’s syndrome is low in India while that of β-thalassemia is moderate. The correlation between the maternal and paternal ages at the time of birth of a Downs syndrome affected person was determined and the analyses showed that there was a positive correlation.

Circulating primitive murine erythroblasts undergo complex proteomic and metabolomic changes during terminal maturation

AbstractPrimitive erythropoiesis is a critical component of the fetal cardiovascular network and is essential for the growth and survival of the mammalian embryo. The need to rapidly establish a functional cardiovascular system is met, in part, by the intravascular circulation of primitive erythroid precursors that mature as a single semisynchronous cohort. To better understand the processes that regulate erythroid precursor maturation, we analyzed the proteome, metabolome, and lipidome of primitive erythroblasts isolated from embryonic day (E) 10.5 and E12.5 of mouse gestation, representing their transition from basophilic erythroblast to orthochromatic erythroblast (OrthoE) stages of maturation. Previous transcriptional and biomechanical characterizations of these precursors have highlighted a transition toward the expression of protein elements characteristic of mature red blood cell structure and function. Our analysis confirmed a loss of organelle-specific protein components involved in messenger RNA processing, proteostasis, and metabolism. In parallel, we observed metabolic rewiring toward the pentose phosphate pathway, glycolysis, and the Rapoport-Luebering shunt. Activation of the pentose phosphate pathway in particular may have stemmed from increased expression of hemoglobin chains and band 3, which together control oxygen-dependent metabolic modulation. Increased expression of several antioxidant enzymes also indicated modification to redox homeostasis. In addition, accumulation of oxylipins and cholesteryl esters in primitive OrthoE cells was paralleled by increased transcript levels of the p53-regulated cholesterol transporter (ABCA1) and decreased transcript levels of cholesterol synthetic enzymes. The present study characterizes the extensive metabolic rewiring that occurs in primary embryonic erythroid precursors as they prepare to enucleate and continue circulating without internal organelles.

New Insights into Hemolytic Anemias: Ultrastructural and Nanomechanical Investigation of Red Blood Cells Showed Early Morphological Changes.

Several diseases are characterized by changes in the mechanical properties of erythrocytes. Hemolytic anemias are an example of these diseases. Among the hemolytic anemias, Sickle Cell Disease and Thalassemia are the most common, characterized by alterations in the structure of their hemoglobin. Sickle cell disease has a pathological origin in synthesizing abnormal hemoglobin, HbS. In contrast, thalassemia results in extinction or decreased synthesis of α and β hemoglobin chains. This work presents a detailed study of biophysical and ultrastructural early erythrocytes membrane alterations at the nanoscale using Atomic Force Microscopy (AFM). Cells from individuals with sickle cell anemia and thalassemia mutations were studied. The analysis methodology in the AFM was given by blood smear and exposure of the inner membrane for ghost analysis. A robust statistic was used with 65,536 force curves for each map, ten cells of each type, with three individuals for each sample group. The results showed significant differences in cell rigidity, adhesion, volume, and roughness at early morphological alterations, bringing new perspectives for understanding pathogenesis. The sickle cell trait (HbAS) results stand out. Significant alterations were observed in the membrane properties, bringing new perspectives for the knowledge of this mutation. This work presents ultrastructural and biomechanical signatures of sickle cell anemia and thalassemia genotypes, which may help determine a more accurate biophysical description and clinical prognosis for these diseases.

Aggregation sickle hemoglobin

Sickle cell disease is a single-cell mutation gene disorder with a substitution of glutamine to valine at the sixth amino acid position in the beta chain hemoglobin. The mutation causes the body to make abnormal hemoglobin that causes the red blood cells to form a crescent shape that is rigid, sticky, and has a lack of iron and oxygen to carry from the lungs to remain parts of the body. Due to the sickle cell mutation, a patient experiences: chronic anemia, chronic damage to organs, episodes of acute pain, priapism, swelling in the hands and feet, delayed growth or puberty, and reduced life expectancy.

A MALDI-TOF mass spectrometry-based haemoglobin chain quantification method for rapid screen of thalassaemia

Background Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. Considering its high prevalence in low and middle-income countries, a cheap, accurate and high-throughput screening test of thalassaemia prior to a more expensive confirmatory diagnostic test is urgently needed. Methods In this study, we constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains in blood, and for the first time, evaluated its diagnostic efficacy in 674 thalassaemia (including both asymptomatic carriers and symptomatic patients) and control samples collected in three hospitals. Parameters related to haemoglobin imbalance (α-globin, β-globin, γ-globin, α/β and α-β) were used for feature selection before classification model construction with 8 machine learning methods in cohort 1 and further model efficiency validation in cohort 2. Results The logistic regression model with 5 haemoglobin peak features achieved good classification performance in validation cohort 2 (AUC 0.99, 95% CI 0.98–1, sensitivity 98.7%, specificity 95.5%). Furthermore, the logistic regression model with 6 haemoglobin peak features was also constructed to specifically identify β-thalassaemia (AUC 0.94, 95% CI 0.91–0.97, sensitivity 96.5%, specificity 87.8% in validation cohort 2). Conclusions For the first time, we constructed an inexpensive, accurate and high-throughput classification model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains and demonstrated its great potential in rapid screening of thalassaemia in large populations. Key messages Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. We constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains to screen for thalassaemia.

Comparison of Leukocyte, Neutrophil, and Lymphocyte Levels in Child Patients that Experienced Breathlessness with COVID-19 and Non-COVID-19 (2020–2021) in Medan, Indonesia

BACKGROUND: COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2. Various risk factors affect the morbidity and mortality of COVID-19, such as age, gender, ethnicity, comorbid conditions, and laboratory parameters. Clinical manifestations of COVID-19 in children are asymptomatic mild degrees or with acute upper respiratory tract symptoms and moderate degrees with clinical pneumonia. In the course of the COVID-19 pandemic, several biomarkers are needed that can be useful in risk stratification to predict the severity and fatality of COVID-19. Several biomarkers are used as markers of disease progression to a critical degree, such as leukocytes, lymphocytes, platelets, interleukin-6, and serum ferritin. Increased leukocytes and neutrophils and decreased lymphocytes are associated with severity and mortality in COVID-19. Laboratory findings in children with COVID-19 include decreased lymphocytes, leukopenia, and increased procalcitonin. In severe COVID-19, children often have abnormal laboratory parameters that suggest a systemic inflammatory response. AIM: This study aims to compare leukocytes, neutrophils, and lymphocytes levels in children with the complaints of shortness of breath with COVID-19 and non-COVID-19 pediatric patients. MATERIALS AND METHODS: This study is an analytic study with a cross-sectional approach to pediatric patients treated in Haji Adam Malik General Hospital Medan with the complaints of shortness of breath. Patient data were assessed based on the characteristic values of hemoglobin, leukocytes, neutrophils, lymphocytes, and COVID-19 polymerase chain reaction results and then analyzed using SPSS for Windows software. The study samples were 276 patients, with 43 confirmed positive COVID-19 patients and 233 negative patients. The source of this research data is data from the patient’s medical record for 1 year (2020–2021). RESULTS: The statistical analysis results found differences in the levels of leukocytes, neutrophils, and lymphocytes in children diagnosed with COVID-19 and non-COVID-19 (p < 0.05). However, there was no difference in hemoglobin levels in children who were congested with COVID-19 and non-COVID-19 (p > 0.05). CONCLUSION: These results are consistent with several cases and previous studies where the levels of leukocytes, neutrophils, and lymphocytes can be used as a detection tool and a diagnostic and prognostic tool in COVID-19 patients.

Effect of Iron Chelator on Renal Function in Thalassemia Patients who Undergo Regular Transfusion

Background: The thalassemia family of genetic disorders is characterized by an abnormal synthesis of the hemoglobin chain, resulting in chronic anemia in some people and clinically asymptomatic in others. There have been very few studies conducted on the effects of thalassemia on the kidneys, which typically included patients treated with deferoxamine having both glomerular and tubular dysfunction. Objective: This research aimed to determine whether kidney dysfunction is observed in young thalassemic individuals manipulating both conventional and primitive markers of kidney dysfunction, and to associate the results to the use of iron chelation therapy. Methods: We measured serum cystatin C (Cys C), tubular phosphorus reabsorption (TPRA), fractional sodium excretion (FNE), and 2-microglobulin, urine calcium, protein, and glucose levels in addition to the usual renal biochemistry. Results: A whole of 42 individuals, ranging in age from 4 to 23, were included in this study and were split into two groups for study (group A taking deferoxamine alone, and group B taking deferiprone coupled with deferoxamine). An increased Cys C level (36%) and proteinuria (24%) were seen in a large percentage of patients, as were tubulopathy with hypercalciuria (35.5 %) and point out 2-MG excretion (33.5 %). Conclusion: Patients with -thalassemia seem to suffer from renal dysfunction even when they are young, so it is important to monitor early signs of renal dysfunction. There is a need for further research into the effect of novel chelators on parameters tubular function. Keywords: Deferiporin, iron chelator, thalassemia, Peshawar, dfo

The journey from blue to pink–a rare cause for self-limiting methemoglobinemia in an Indian baby

Abstract Objectives To describe a rare case of methemoglobinemia in a newborn baby with excellent prognosis. Methemoglobinemia in the neonatal period is very rare and when present is usually caused by environmental toxicity from strong oxidizing agents and rarely due to enzyme deficiency or inherited disorders of hemoglobin metabolism. Case presentation We report a newborn baby presented with cyanosis and desaturation right from birth, later found to have methemoglobinemia and started medication. Genetic evaluation revealed a mutation in the gamma chain of fetal haemoglobin (HbF) causing abnormal hemoglobin. Physiologically significant mutations in gamma-globin genes cause symptoms in the fetus and neonate that gradually abate in the first few months of life. Conclusions Genetic evaluation is advisable in babies with unexplained methemoglobinemia as the prognosis of the condition depends on the underlying mutation. Early diagnosis of methemoglobinemia due to gamma chain mutation in HbF as in our case helps in reassuring the parents and also in preventing unnecessary aggressive investigations.

Alpha haemoglobin helps high-altitude deer mice breathe more deeply

No self-respecting crime drama would be the same without a liberal sprinkling of blood. Yet, the haemoglobin that gives blood its distinctive shade has a perfectly mundane role, transporting oxygen around the body and returning CO2 to the lungs. The haemoglobin of animals, such as deer mice (Peromyscus maniculatus), that live at high altitude is also specially adapted to pick up oxygen when the air is much thinner than that experienced by species nearer to sea level. But Catherine Ivy from McMaster University, Canada, explains that simply breathing more deeply can also increase the amount of oxygen getting into an animal's body when the air pressure falls: high-altitude deer mice breathe more slowly and deeply than lowland mice. There were also hints that members of the haemoglobin family of proteins that occur in other parts of the body, such as the nervous system, might be able to control how an animal breathes. Could the specialised haemoglobin that allows high-altitude deer mice to carry sufficient oxygen also help the animals breathe more deeply?Ivy and Graham Scott (McMaster University) decided to find out, so they enlisted the help of Zachary Cheviron (University of Montana, USA) and Jay Storz (University of Nebraska, USA) to breed mice that carried specific combinations of the high- and low-altitude haemoglobins, to check how the proteins affected the animals’ breathing. The team, including colleagues from Canada and the USA, collected deer mice from Mount Evans, CO, USA, living at 4350 m, and from Nine Mile Prairie, NB, USA, living at 430 m, before transporting the animals to Cheviron's lab at 978 m in Montana. There, Rena Schweizer, Jonathan Velotta and Shane Campbell-Staton allowed a high-altitude male to have a family with a low-altitude female and those offspring to interbreed before Natalie Gutierrez-Pinto and Chandrasekhar Natarajan (both from University of Nebraska) checked the youngsters’ DNA to be certain which combinations of the high- and low-altitude haemoglobins they carried.Once the mice were a year old, they joined Ivy at McMaster University, where they remained at an altitude of 50 m for 8 weeks before she recorded their breathing as she lowered the air pressure, to simulate the animals climbing in altitude. Then, she transferred the mice to a pressure chamber where she could simulate life at 4300 m and rechecked their breathing after 8 weeks.Sure enough, as the air grew thinner, all of the mice breathed more to compensate for the effective lack of oxygen. However, when Ivy compared the haemoglobin combinations that the mice had inherited with their breathing patterns, it was clear that the animals that had inherited two high-altitude forms of the alpha chain component of haemoglobin were taking particularly slow and deep breaths. In contrast, the mice that only inherited low-altitude versions of the alpha haemoglobin chain breathed more shallowly. And when Ivy compared the breathing patterns of the specially bred mice with the patterns of mice that had arrived directly from the mountains, they were essentially indistinguishable. Having high-altitude versions of the haemoglobin α chain seems to be key to regulating how deer mice breathe.‘Our findings are against the dogma that globins don't affect breathing’, says Ivy, and she is keen to find out whether the red blood cells, or some other tissue, are the source of the haemoglobin α chain that seems to be crucial to the mountain deer mouse's laid-back breathing style.

Association of Body mass index and serum ferritin level in pediatrics with Beta-thalassemia major disease

Background: Beta-thalassemia major is a type of inherited blood disease that results in variable outcomes such as severe anemia due to haemoglobin chains. Recurrent and lifelong blood transfusions as a treatment in beta-thalassemia major disease lead to iron deposition in various organs and cause the failure of multiple organs. Failure of affected organs leads to Body mass index (BMI) abnormality. This study aimed to evaluate the association between BMI and serum ferritin level as a marker for iron overload. Materials and Methods: A cross-sectional study designed and conducted with total number of 740 paediatrics, with mean age about 14.2±8.7 years old and with beta-thalassemia major requiring recurrent blood transfusion. Patient information, including demographics, serum ferritin level and percentage of BMI, was recorded and analysed by SPSS 25.0 and the statistical significant level, considered as 0.05. Results: A total number of 740 paediatrics with beta-thalassemia major disease (mean age about 14.2±8.7 years) were included to study to examine the association between serum ferritin level and their BMI. The total mean serum level of ferritin calculated about 3326 ± 3859 Nanogram/mililitter (ng/ml). Totally, 447 (60.4%) case of them had BMI percentile less than 5%, 274 (37.02%), 16 (2.16%) and 3 (0.4%) had BMI percentile 5%-85%, 85%-95% and more than 95%. There was no relation between gender and serum ferritin levels. The relationship between age and BMI has been positive (P=0.002). Finally, it resulted that there was a negative relationship between the BMI percentile and mean serum ferritin levels in paediatrics with beta-thalassemia major (P=0.031). Conclusion: Frequent Blood transfusion is associated with elevated serum ferritin level in paediatrics with beta-thalassemia major disease and experiencing lower percentiles of BMI in these patients.

Dynamics of camel and human hemoglobin revealed by molecular simulations

Hemoglobin is one of the most widely studied proteins genetically, biochemically, and structurally. It is an oxygen carrying tetrameric protein that imparts the characteristic red color to blood. Each chain of hemoglobin harbors a heme group embedded in a hydrophobic pocket. Several studies have investigated structural variations present in mammalian hemoglobin and their functional implications. However, camel hemoglobin has not been thoroughly explored, especially from a structural perspective. Importantly, very little is known about how the heme group interacts with hemoglobin under varying conditions of osmolarity and temperature. Several experimental studies have indicated that the tense (T) state is more stable than the relaxed (R) state of hemoglobin under normal physiological conditions. Despite the fact that R state is less stable than the T state, no extensive structural dynamics studies have been performed to investigate global quaternary transitions of R state hemoglobin under normal physiological conditions. To evaluate this, several 500 ns all-atom molecular dynamics simulations were performed to get a deeper understanding of how camel hemoglobin behaves under stress, which it is normally exposed to, when compared to human hemoglobin. Notably, camel hemoglobin was more stable under physiological stress when compared to human hemoglobin. Additionally, when compared to camel hemoglobin, cofactor-binding regions of hemoglobin also exhibited more fluctuations in human hemoglobin under the conditions studied. Several differences were observed between the residues of camel and human hemoglobin that interacted with heme. Importantly, distal residues His58 of α hemoglobin and His63 of β hemoglobin formed more sustained interactions, especially at higher temperatures, in camel hemoglobin. These residues are important for oxygen binding to hemoglobin. Thus, this work provides insights into how camel and human hemoglobin differ in their interactions under stress.

Thalassemia Major and Associated Psychosocial Problems: A Narrative Review.

Thalassemia is an inherited disease that causes the production of damaged hemoglobin chains. Patients are diagnosed with thalassemia major due to major clinical signs and deep anemia. This study aimed to examine the major thalassemia and psychosocial aspect of it, which is such an important issue, to serve as a roadmap for better handling these patients and to contribute to the literature. The method used in this study was narrative review. A literature review was conducted by searching the materials published in databases including Web of Science, PubMed, Scopus, and Google Scholar search engine from 2001 to 2020. Besides WHO website was searched. Thalassemia major damages the heart, liver, lungs and endocrine organs due to anemia and iron accumulation. In addition, the patient may experience mental and social problems due to the congenital nature of the disease and its lifelong duration. The psychosocial problems and treatment burdens of thalassemia patients are very high. There are many studies about the prevalence and physical consequences of thalassemia. However, there are not enough articles and researches describing the psychosocial effects of thalassemia on patients and what can be done about these effects. For this reason, this paper focuses on the process of thalassemia and the psychosocial problems it creates to contribute to the literature and to be a roadmap for better handling these patients.

Role of Curcumin in Beta Thalassemia: A Review

Beta-thalassemia is an inherited blood disorder characterized by defective beta chains of hemoglobin which often lead to the development of anemia. These patients require periodic blood transfusions to compensate for anemia. However, these transfusions often lead to complications such as iron overload. This abnormal hemoglobin can lead to anemia and cause other medical problems. Curcumin which is a polyphenol has anti-inflammatory properties and also can increase the number of antioxidants in the body. The main aim of the study is to determine the efficiency of curcumin in the treatment of β-Thalassemia.
 The administration of curcumin in the treatment of β-Thalassemia has aided to be beneficial. Curcumin also exhibited hepatoprotective properties as serum bilirubin decreased in the β-Thalassemia patients. Supplementation of curcumin is seen to improve insulin resistance, lipid profile, and systemic inflammation by reducing HOMA-IR, TG, TG/HDL ratio, and hs-CRP levels. Curcumin when used in the treatment for β-Thalassemia showed low or no side effects. It has powerful anti-inflammatory effects and acts as a potent antioxidant where it can neutralize the free radicals due to its chemical structure.

Non-Immune Hemolytic Anemia (Hemoglobinopathy)

Hemoglobinopathy is an autosomal recessive disorder that is classified into 2 major groups, namely thalassemia syndromes and structural variants of the hemoglobin chain. Thalassemia is a group of genetic disorders caused by decreased speed of chain synthesis or. The second group, structural abnormalities in the hemoglobin chain, often causes a condition called sickle cell (sickle cell anemia), this structural abnormality occurs due to the substitution of adenine by thymine which causes the conversion of the amino acid glutamate to valine. 7% of the world's population are carriers of hemoglobinopathies. This type of research is literature research or literature review. Based on data from the Indonesian Thalassemia Foundation (YTI) in 2008-2017, 5.8% of thalassemia carriers were found from 12,038 people examined, and 28.62% of 4,137 people according to the results of family screening. thalassemia in 2009-2017. The prognosis of thalassemia disease depends on medication adherence and the type of thalassemia suffered. Death in patients with sickle cell anemia is usually due to co-morbidities such as renal and other organ failure. Early and adequate symptom management can improve the prognosis. This disorder is autosomal recessive which is classified into 2 major groups, namely thalassemia syndrome and structural variants of hemoglobin chains that often produce sickle cell shape

A Phase 2a Study Evaluating the Safety and Pharmacokinetics (PK) of Luspatercept in Pediatric Patients with Transfusion-Dependent β-Thalassemia (TDT)

A Phase 2a Study Evaluating the Safety and Pharmacokinetics (PK) of Luspatercept in Pediatric Patients with Transfusion-Dependent β-Thalassemia (TDT)