Potential Use of MicroRNA Technology in Thalassemia Therapy.

Thalassemia encompasses a group of inherited hemoglobin disorders characterized by reduced or absent production of the α- or ß-globin chains, leading to anemia and other complications. Current management relies on lifelong blood transfusions and iron chelation, which is burdensome for patients. This review summarizes the emerging therapeutic potential of modulating microRNAs (miRNAs) to treat thalassemia. MiRNAs are small non-coding RNAs that regulate gene expression through sequence-specific binding to messenger RNAs (mRNAs). While they commonly repress gene expression by binding to the 3' untranslated regions (UTRs) of target mRNAs, miRNAs can also interact with 5'UTRs and gene promoters to activate gene expression. Many miRNAs are now recognized as critical regulators of erythropoiesis and are abnormally expressed in ß-thalassemia. Therapeutically restoring levels of deficient miRNAs or inhibiting overexpression through miRNA mimics or inhibitors (antagomir), respectively, has shown preclinical efficacy in ameliorating thalassemic phenotypes. The miR-144/451 cluster is especially compelling for targeted upregulation to reactivate fetal hemoglobin synthesis. Advances in delivery systems are addressing previous challenges in stability and targeting of miRNA-based drugs. While still early, gene therapy studies suggest combinatorial approaches with miRNA modulation may provide synergistic benefits. Several key considerations remain including enhancing delivery, minimizing off-target effects, and demonstrating long-term safety and efficacy. While no miRNA therapies have yet progressed to clinical testing for thalassemia specifically, important lessons are being learned through clinical trials for other diseases and conditions, such as cancer, cardiovascular diseases, and viral. If limitations can be overcome through multi-disciplinary collaboration, miRNAs hold great promise to expand and transform treatment options for thalassemia in the future by precisely targeting pathogenic molecular networks. Ongoing innovations, such as advancements in miRNA delivery systems, improved targeting mechanisms, and enhanced understanding of miRNA biology, continue to drive progress in this emerging field towards realizing the clinical potential of miRNA-based medicines for thalassemia patients.

Expressions of Progesterone Receptor of Orbital Meningiomas in Indonesia.

OBJECTIVE: Visual disturbances that can heal after a complete resection of orbital meningiomas are only about 2.9%. Grading and expression of the progesterone receptor (PR) in orbital meningiomas, according to World Health Organization (WHO) is a useful predictive value of recurrence in the treatment management of orbital meningiomas. This study aims to determine the relationship of PR expression on the grading of orbital meningiomas as tumour prognostic factors. METHODS: This cross-sectional observational analysis observed 44 orbital meningioma in Cicendo Eye Hospital Bandung and Hasan Sadikin Hospital between 2017-2020. We performed of mRNA PR with RT-qPCR technique and calculation with the 2∆∆Ct formula. Statistical analysis used the Kruskal-Wallis Test, followed by the Mann-Whitney post hoc test with p<0.005. RESULTS: Relative expression of mRNA PR in meningioma orbita grade I to grade III decreased significantly the expression of relative mRNA PR at grade I, II, III of 21.69±44.35, 20.39±26.30 and 1.25±0.85, with Kruskal-Wallis test, p =0.007. Mann Whitney's test results showed relative mRNA PR expression between grades I and II not different (p = 0.055), relative expression mRNA PR between grades I and III differed significantly (p = 0.024), and relative expression mRNA PR between grades I and III was not different (p = 0.638). CONCLUSION: mRNA PR expression is viable for prognostic value, predicting recurrence and implementing more effective management of subsequent therapy, it must be combined with other markers to determine the nature of the orbital meningioma.

Cd60 (GTG > GAG)/Hb Cagliari mutation was found in scanning of ß-thalassemia alleles from patients of East Kalimantan, Indonesia.

BACKGROUND AND PURPOSE: Thalassemia is a genetic disorder with a fairly high prevalence worldwide. Three to 10% of Indonesian people are estimated to be carriers for thalassemia. This study was intended to figure out the spectrum of genetic mutations of patients with thalassemia in Samarinda City, East Kalimantan. METHODS: The research subjects consisted of 31 ß-thalassemia patients registered with the Association of Thalassemia Patients' Parents (POPTI) of Samarinda. DNAs were extracted from the patients' blood samples then amplified by the direct sequencing technique with polymerase chain reaction to analyze ß-globin gene mutations. RESULT: The study results show that the male/female ratio was 51.6%:48.4%, the patients' ages ranged from 4 years to 56 years with an average age of 14 years, and the dominant ethnic group was Javanese (64.5%). The DNA analysis yielded 7 types of mutant alleles, namely Cd26/HbE (GAG>AAG) at 48.4%, IVS-1-5 (G > C) at 14.5%, IVS-1-2 (T > C) at 12.9%, Cd35 (-C) at 8.1%, IVS-1-1 (G > T) at 6.5%, and, the least frequently encountered mutant alleles, Cd30 (AGG > ACG) and Cd60 (GTG > GAG) each at 3.2%. CONCLUSION: This study discovered unreported mutant in Indonesia, namely Cd60 (GTG > GAG).

Biochemical and histopathological effects of green tea nanoparticles in ironized mouse model.

Transfusion in the treatment of thalassemia gives rise to iron deposits in many organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron chelating agent, it is important to find another alternative therapy that can act as iron chelation. The study aims to compare the histopathological pictures of the heart and spleen in iron-induced rats after administration of DFO and nanoparticles of green tea extract. The research used experimental research design with a post-test only control group. Experimental nano green teas were divided into four treatment groups; no diet, DFO supplementation, nano green tea supplementation, and a combination of both DFO and green tea. Ferritin and glutathione peroxides were used as biochemical parameters, and histopathological pictures of the heart and spleen were recorded. The study showed that there was significant improvement in the rats receiving DFO and nanoparticles of green tea compared with the rats in the no diet group. The study also reported that nano green tea has an effect comparable to DFO.

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on ß-thalassemia and hemoglobin E/ß-thalassemia patients in Indonesia.

OBJECTIVE/BACKGROUND: Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of ß-thalassemia (ß-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB), among ß-thal and HbE/ß-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among ß-thal and HbE/ß-thal patients in Indonesia. METHODS: A total of 189 patients with genotyping of ß-thal and HbE/ß-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of ß-thal and HbE/ß-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) methods. RESULTS: The distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/ß-thal patients, but rs9399137 did not demonstrate such features. In ß-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance. CONCLUSION: The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/ß-thal patients in Indonesia, but not in ß-thal patients.

Molecular Scanning of ß-Thalassemia in the Southern Region of Central Java, Indonesia; a Step Towards a Local Prevention Program.

Thalassemia is the most prevalent genetic blood disorder worldwide, and particularly prevalent in Indonesia. The purpose of this study was to determine the spectrum of ß-thalassemia (ß-thal) mutations found in the southern region of Central Java, Indonesia. The subjects of the study included 209 ß-thal Javanese patients from Banyumas Residency, a southwest region of Central Java Province. DNA analysis was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS), and the direct sequencing method. The results showed that 14 alleles were found in the following order: IVS-I-5 (G > C) (HBB: c.92 + 5G > C) 43.5%, codon 26 (Hb E; HBB: c.79G > A) 28.2%, IVS-I-1 (G > A) (HBB: c.92 + 1G > A) 5.0%, codon 15 (TGG > TAG) (HBB: c.47G > A) 3.8%, IVS-I-1 (G > T) (HBB: c.92 + 1G > T) 3.1%, codon 35 (-C) (HBB: c.110delC) 2.4%. The rest, including codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), codons 8/9 (+G) (HBB: c.27_28insG), codon 19 (AAC > AGC) (HBB: c.59A > G), codon 17 (AAG > TAG) (HBB: c.52A > T), IVS-I-2 (T > C) (HBB: c.92 + 2T > C), codons 123/124/125 (-ACCCCACC) (HBB: c.370_378delACCCCACCA), codon 40 (-G) (HBB: c.123delG) and Cap +1 (A > C) (HBB: c.-50A > C), accounted for up to 1.0% each. The most prevalent alleles would be recommended to be used as part of ß-thal screening for the Javanese, one of the major ethnic groups in the country.

Status of Superoxide Dismutase in Transfusion Dependent Thalassaemia.

BACKGROUND: Thalassemia is a collection of genetic impairments in beta and alpha genes causing various states of anemia. Severe types of the disease need lifelong transfusions, leading to oxidant-antioxidant disturbance due to massive iron deposits. AIMS: The aim of this study was to assess the antioxidant enzyme Superoxide Dismutase (SOD) and ferritin levels of thalassemia major patients in a peripheral health facility. MATERIALS AND METHODS: Two hundred and nine probands were recruited and performed laboratory experiments for SOD and Ferritin levels. Chelation administration and clinical score were taken from interviewing the family and from medical report data. RESULTS: The study showed that SOD intensity was lower (162.41 u/ml) compared to the normal cutoff point (P = 0.001), while the mean of Ferritin levels was ten times over the normal value (4226,67 ng/dl). Observations also reported that chelation medicine was not administrated properly. CONCLUSIONS: The data indicates that thalassemic patients have oxidant-antioxidant uproar due to oxidative stress. Monitored chelating administration, selective antioxidant, and a well-balanced diet may prevent oxidative injury.