Cognitive impairment and hippocampal neuronal damage in ß-thalassaemia mice.

ß-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in ß-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of ß-thalassaemia intrinsic factors, 22-month-old ß-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in ß-thalassaemia. Open field test showed that ß-thalassaemia mice had decreased motor function. However, no difference of neuronal degeneration in primary motor cortex, layer 2/3 area was found. Interestingly, impaired learning and memory function accessed by a Morris water maze test was observed and correlated with a reduced number of living pyramidal neurons in hippocampus at the CA3 region in ß-thalassaemia mice. Cognitive impairment in ß-thalassaemia mice was significantly correlated with several intrinsic ß-thalassaemic factors including iron overload, anaemia, damaged red blood cells (RBCs), phosphatidylserine (PS)-exposed RBC large extracellular vesicles (EVs) and PS-exposed medium EVs. This highlights the importance of blood transfusion and iron chelation in ß-thalassaemia patients. In addition, to improve patients' quality of life, assessment of cognitive functions should become part of routine follow-up.

Graves' Disease: Acquired Cause of a Moderate Increase in Hemoglobin A2 Level.

BACKGROUND: Hyperthyroidism can lead to diverse hematological disorders, such as microcytosis and a mild increase in hemoglobin A2 fraction. METHODS: This study reported a 31-year-old woman of Moroccan origin recently diagnosed with Graves' disease. Her blood tests revealed microcytosis, hypochromia, and a normal ferritin level. A phenotypic analysis of hemo-globin was performed using two techniques: capillary electrophoresis and reversed-phase high performance liquid chromatography. RESULTS: Both techniques indicated a slight increase in hemoglobin A2 level. These results initially suggested het-erozygous beta-thalassemia, eventually correlating with the concurrent presence of Graves' disease, as evidenced by the normalization of hemoglobin A2 level following treatment. CONCLUSIONS: This case highlights the importance of having clinical, biological, and therapeutic data for a relevant interpretation of a phenotypic hemoglobin study.

Brain perfusion changes in beta-thalassemia.

BACKGROUND: Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce. AIMS: We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity. METHODS: We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded. RESULTS: Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found. CONCLUSION: Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial.

BACKGROUND AND AIM: Frequent administration of blood in ß-thalassemia patients can lead to over-loaded iron, a reduction in the levels of antioxidant activities in the body, and oxidative stress. This study was done to evaluate the antioxidant and protective effect of aqueous oak (Quercus brantii) extract supplementation on these patients. METHODS: This clinical trial was performed on 60 major ß thalassemia patients dividing them into intervention and control groups. In addition to taking desferrioxamine (DFO), the control and intervention groups received respectively placebo capsule supplementation and aqueous Quercus extract capsules (300 mg/day) for 3 months. Serum lipid profiles (LDL-c, HDL-c, triglyceride), Total Antioxidant Capacity (TAC), Glucose, Uric acid, urea nitrogen (BUN), Creatinine, LFT (Liver Function Tests) such as SGOT, SGPT, ALP, Total bilirubin, Direct bilirubin, ferritin, MDA and carbonyl protein (CO) levels were measured before and after the period. In addition, the activity of catalase (CAT), and superoxide dismutase (SOD) was measured in the red blood cell. Furthermore, antioxidant activity and total phenolic content of aqueous Quercus were recorded to standardize capsule formulation. RESULTS: Mean serum MDA, and protein CO, significantly decreased in the intervention group with ß-TM after 3 months of treatment with Quercus extract. In addition, the superoxide dismutase (SOD) enzyme and Total antioxidant capacity (TAC) significantly increased in comparison with the control group. Changes in serum creatinine, BUN, and alanine transferase were not significant. In the study, Quercus extract capsules contain 48/56 mg gallic acid/g (dry extract) total phenol, 58/6 mg/g (dry extract), and flavonoids of 63/8 µg/ml antioxidant power which by GC/MS analysis has been measured. At the end of the study, serum MDA decreased from 48.65 ± 8.74 to 43.94 ± 10.39 µ mol/l after administration of oak extract and protein CO dropped from 2.44 ± 0.38 to 1.2 ± 0.31 nmol DNPH/mg protein after administration of the oak extract. At the end of the study serum, TAC increased in patients interventional group from 907 ± 319 to 977 ± 327 µmol FeSO4/l compared to the control group 916 ± 275 to 905.233 ± 233 µmol FeSO4/l with placebo, and SOD increased from 1577 ± 325 to 2079 ± 554 U/l (compared to 1687 ± 323 U/l with placebo). The treatment effect of Quercus was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and SOD, with significant effects being demonstrated for each laboratory parameter (P = 0.15, P = 0.001, P = 0.02, and P < 0.003, respectively). CONCLUSIONS: Aqueous Quercus extract, due to its high antioxidant potential, reduced MDA, serum carbonyl protein, and increased superoxide dismutase activity effectively decreased serum OS and enhanced serum antioxidant capacity in patients with ß-thalassemia major. oak given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients. REGISTRATION INFORMATION: This study was submitted, evaluated, and approved by the Iranian Registry of Clinical Trials (IRCT: http://www.irct.ir; IRCT2015101411819N4), which was established for national medical schools in Iran.

[Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province].

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

COMPARATIVE STUDY OF OXIDATIVE STRESS IN PATIENTS WITH Β -THALASSEMIA MAJOR ON DEFERASIROX VERSUS DEFEROXAMINE THERAPY.

Accumulation of iron in vital organs is increasingly challenging in clinical settings during the lifespan of thalassemia patients. Iron overload hurdle these organs to redox imbalances. Commonly used iron-chelating agents in (deferasirox and, deferoxamine) could have a positive antioxidant role. Therefore, the aim of this study was designed to compare the effects of deferasirox and, deferoxamine, iron-chelating agents in oxidative stress in patients with ß-thalassemic major. In this case series comparative study, 60 known cases of ß-thalassemic patients receiving chelating agents therapy were divided into two groups of thirty, group one consisted of 30 patients 16 male and14 female, who received oral agent deferasirox tablets at dose 20-40mg/kg. Group two consisted of 30 patients, 16 male and 14 female, on intravenous therapy with Deferoxamine at a dose of 20-50mg/kg, Another thirty healthy individuals matched with age and gender, were kept as a control group. Total antioxidant capacity (TAOC) and Malondialdehyde (MDA) were measured in all studied groups. The three groups were similar in terms of age, and gender, A statistically non-significant difference in age (p>0.05) existed between the control and patient groups (10.9±2.93; 11.2±4.1*;11.6±3.6*) respectively. The number of patients in to control group and male-to-female numbers were matched since the ratios were similar. A statistically non-significant difference in BMI (p>0.05) existed between the control and patient groups (17±2, 17.2±2, 18±2.4*) respectively. TAOC is lower in-patient groups, when compared with the control group (27.8 ± 10.7; 32.5 ± 10.2; and 79.5 ± 7 u/ml) respectively, while the MDA value is higher when compared with the control group (7.2±4.6 and, 6.6±4.42; and 0.57±0.26; nmol/ml) respectively. The TAOC in patients group on Deferoxamine, is higher, while MDA is lower than in patients on Defrasirox. The TAOC in patients was reduced and Oxidative stress was enhanced in patients with thalassemia. Deferoxamine is more effective in modulating redox status.

ß-Thalassemia gene editing therapy: Advancements and difficulties.

ß-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of ß-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent ß-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of ß-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of ß-thalassemia diseases.

Effects of Splenectomy on Natural Killer Cell Levels in ß-Thalassemia Major Patients.

AIM: In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with ß-thalassemia major (ß-TM). MATERIALS AND METHODS: Seventy patients with ß-TM (38 splenectomized and 32 nonsplenectomized) and 25 healthy controls were included in this study. The hemogram parameters, ferritin, T lymphocyte, T-helper cell, T-suppressor cell, and NK cell numbers, were measured. RESULTS: The T lymphocyte (CD3+) level was found to be significantly higher in the patient group (p < 0.05). CD3+/CD4+ T lymphocytes were detected to be significantly higher in the patient group (p < 0.05). Although the CD3+/CD4+ T lymphocyte level was significantly higher in the nonsplenectomy group (p < 0.05), this was not the case in the splenectomy group. When the patient and control groups were compared, no significant difference was detected regarding CD3+/CD8+ T lymphocyte levels. CD3-/CD16+CD56+ NK cell level was found to be significantly lower only in the splenectomy group than in the control group (p < 0.05). We found that there was a significant negative correlation between serum ferritin levels and both total lymphocyte (r = -0.617) and CD3+ lymphocyte (r = -0.718) levels in the control group (p < 0.05). A significant negative correlation was detected between serum ferritin levels and CD3-/CD16+CD56+ NK cell levels in the patient group (r = -0.410) (p < 0.05). CONCLUSION: Splenectomy reduces NK cell levels in patients with ß-TM. The negative relationship between ferritin levels and NK cells indicates that ferritin levels should be kept under control in patients with ß-TM.

Evaluation of anti-sickling effects of two varieties of Cajanus cajan (L.) Huth on sickle cell beta thalassemia.

ETHNO-PHARMACOLOGICAL RELEVANCE: Globally, the prevalence of sickle cell disease is on the rise, with developing countries experiencing particularly alarming mortality rate compared to developed nations. The World Health Organization (WHO) and United Nations (UN) have acknowledged sickle cell disease as a significant global public health concern. Unfortunately, a cure for this condition is yet to be discovered, and existing allopathic treatments, while offering relief, come with serious side effects. In recent times, there has been a growing interest in exploring the potential of medicinal plants for treating sickle cell disease due to their content of secondary metabolites that may impact the disease's mechanisms. Cajanus cajan, a crucial grain legume in rain-fed agriculture in semi-arid tropics, has been traditionally used in folk medicine to manage various illnesses and is suggested to possess anti-sickling properties. AIM OF THE STUDY: The present study investigated two varieties of C. cajan for their effectiveness in treating sickle cell beta thalassemia, a variant of sickle cell disease. MATERIALS AND METHODS: The study was divided into four groups consisting of the untreated group (group 1), group treated with standard drug (group 2), group treated with white C. cajan (group 3) and group treated with brown C. cajan (group 4). The effects of the two variety of C. cajan were measured by polymerization test, reversibility test, osmotic fragility test, deoxygenation and beta globin synthesis test. RESULT: The results revealed that both varieties of C. cajan demonstrated a reduction in polymerization rates, reversed sickled red blood cells, increased the oxygen affinity of Hb-S/ß, elevated the Fe2+/Fe3+ ratio, and maintained the membrane stability of red blood cells. Notably, the white variety exhibited superior anti-sickling properties compared to the brown variety. CONCLUSION: This suggests that this significant leguminous crop could be utilized for the treatment and management of sickling disorders, particularly in low-income countries where conventional treatments may be financially inaccessible to patients.

Relationship of TNFα-238 G/A (rs 361525) genotypes with TNFα gene expression in liver and pancreas disorders in sample of beta thalassemia major adult Iraqi patients.

BACKGROUND: Tumor necrosis factor-α (TNFα) is a crucial physiologic regulator of immune responses, and several disorders have been associated with its dysregulation. OBJECTIVE: This study aimed to understand TNFα gene expression in adult patients with liver and pancreas disorders and examine the impact of TNFα-238 genotypes on this population. METHODS: At the Ibn Al-Baladi Hospital in Baghdad, blood samples were collected from forty patients who were diagnosed with beta thalassemia together with pancreatic disease, forty patients who were diagnosed with thalassemia together with liver disorder, and forty patients who were diagnosed with thalassemia without pancreas or liver disorder. For the purpose of establishing a control group, forty samples were collected from persons who were of the same age and gender and seemed to be in good health. All of these individuals were deemed to be older than 18 years old. Through the utilization of real-time polymerase chain reaction (PCR), the level of TNF-α gene expression was investigated and assessed. The T-ARMS-PCR method was performed for detection and genotyping of TNFα-238 in thalassemia patients and healthy control samples. RESULTS: The result showed that TNF α gene expression assessment showed that group B (thalassemia patients with liver disorder) had higher folding than other groups while the lowest gene expression was in group D (as control group). Furthermore, the relationship between TNFα gene expressions folding with TNFα-238 genotypes in beta thalassemia major patients, discovered a considerable increase at GA genotype patients in TNFα gene expression level, followed by AA genotype compared to the GG genotype. Furthermore, the results of the current study showed an association between the presence of the mutant (A) allele whether heterozygous (GA) and homozygous (AA) with the TNF-α gene expression in thalassemia patients with liver and pancreatic disorders. CONCLUSION: Based on the results, it can be concluded that there is a relationship between the presence of the mutant (A) allele, whether heterozygous (GA) or homozygous (AA) of TNF-α 238, and TNF-α gene expression in liver and pancreatic diseases as well as in patients with thalassemia.

Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent ß-thalassemia patients who remained on the same monotherapy over 10 years.

We conducted a retrospective cohort study on 663 transfusion-dependent ß-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload.

Molecular characterization of similar Hb Lepore Boston-Washington in four Chinese families using third generation sequencing.

Hemoglobin (Hb) Lepore is a rare deletional δß-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and ß-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband's wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.

Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand.

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Newborn Screening for ß-Thalassemia Identifies a Complex Genotype Involving a Novel ß-Globin Gene Mutation (HBB:c.336dup).

Newborn screening identified a Chinese-Canadian infant who was positive for possible ß-thalassemia (ß-thal). Detailed family studies demonstrated that the proband was a compound heterozygote for the Chinese Gγ(Aγδß)0-thal deletion and a novel frameshift mutation within exon 3 (HBB:c.336dup), and heterozygous for the Southeast Asian α-thal deletion (--SEA/αα). This case illustrates the importance of follow-up molecular testing of positive newborn screening results to confirm the diagnosis and define risks for future pregnancies.

miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4.

Oxidative damage to erythroid cells plays a key role in the pathogenesis of thalassemia. The oxidative stress in thalassemia is potentiated by heme, nonheme iron, and free iron produced by the Fenton reaction, due to degradation of the unstable hemoglobin and iron overload. In addition, the levels of antioxidant enzymes and molecules are significantly decreased in erythrocytes in α- and ß-thalassemia. The control of oxidative stress in red blood cells (RBCs) is known to be mediated by microRNAs (miRNAs). In erythroid cells, microR-214 (miR-214) has been reported to respond to external oxidative stress. However, the molecular mechanisms underlying this phenomenon remain unclear, especially during thalassemic erythropoiesis. In the present study, to further understand how miR-214 aggravates oxidative stress in thalassemia erythroid cells, we investigated the molecular mechanism of miR-214 and its regulation of the oxidative status in thalassemia erythrocytes. We have reported a biphasic expression of miR-214 in ß- and α-thalassemia. In the present study the effect of miR-214 expression was investigated by using miR -inhibitor and -mimic transfection in erythroid cell lines induced by hemin. Our study showed a biphasic expression of miR-214 in ß- and α-thalassemia. Subsequently, we examined the effect of miR-214 on erythroid differentiation in thalassemia. Our study reveals the loss-of-function of miR-214 during translational activation of activating transcription factor 4 mRNA, leading to decreased reactive oxygen species levels and increased glutathione levels in thalassemia erythroid cell. Our results suggest that the expression of activating transcription factor 4 regulated by miR-214 is important for oxidative stress modulation in thalassemic erythroid cells. Our findings can help to better understand the molecular mechanism of miRNA and transcription factors in regulation of oxidative status in erythroid cells, particularly in thalassemia, and could be useful for managing and relieving severe anemia symptoms in patients in the future.

Premarital Screening is Pivotal in Reducing the Births of Babies Affected with Thalassemia Major in Iraq.

Thalassemia major is one of the health problems in Iraq, especially in Kurdistan. Pre-marriage mandatory preventive screening program was established in Kurdistan in 2008, which allowed us to study the prevalence of different hemoglobinopathies among newly married young adults in this region. A total of 1154 subjects (577 couples) attending the Koya district, premarital Health center, were screened using red cell indices. Those who had mean corpuscular volume (MCV)<80 fl and mean corpuscular hemoglobin (MCH)<27 pg had high-performance liquid chromatography and iron studies. Out of 1154 individuals that were evaluated, 183 (11.9%) had low MCV and MCH. Of the former 183 subjects, 69 (5.97%) had ß-thalassemia trait, 10 (0.86%) had δß-thalassemia trait, and no other hemoglobinopathies were recorded in our study. There was second-degree consanguinity in 4.7% of all 577 couples. In two couples, both partners had ß-thalassemia trait and both were consanguineous. Both couples decided to separate after counseling. Based on the current study, the role of the premarital screening program in decreasing the number of new thalassemia major cases among the Kurdish population is laudable. Therefore, mandatory premarital screening is advised in all parts of Iraq.

[Advance of research on the role of BCL11A in the occurrence and treatment of ß-Thalassemia].

ß-Thalassemia is a single-gene disease caused by mutations in ß-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/ß hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for ß-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of ß-thalassemia.