Iron Chelator Research Articles

Iron consumption strengthens anti-tumoral STING activation mediated by manganese-based nanoparticles

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, as an important part in innate immunity, has recently emerged as a promising target for improving tumor therapy. Manganese ions (Mn2+) are an emerging agonist in the cGAS-STING pathway with multifaceted advantages, however manganese-based nanoparticles alone as the Mn2+ source have shown limited activity in eliciting anti-tumor immune responses compared to conventional organic STING agonists, and the underlying mechanism of the suboptimal efficiency remains unclear. Here, we demonstrate that intratumoral iron ions attenuate manganese-induced anti-tumor STING activation, and that the utilization of deferoxamine (DFO), an iron chelator that depletes intratumoral iron ions, effectively increases the intracellular accumulation of Mn2+ and thus promoted the STING activation efficiency of a hyaluronic acid modified manganese carbonate-silica hybrid nanoparticle (DS@Mn-H) in macrophages. The mechanism study suggests that the addition of DFO inhibited the expression of ferroportin (FPN), which serves as a Mn2+ exporter to reduce intracellular Mn2+ level. The synergistic effect of DS@Mn-H and DFO achieved excellent anti-tumor activities in a mouse colon carcinoma model. This work provides new insights on improving the Mn-based metallo-immunotherapy of cancer.

Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer.

Iron accumulation in tumors contributes to disease progression and chemoresistance. Although targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells toward an immunostimulatory state characterized by the production of type-I IFN and overexpression of molecules that activate NK cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type-I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T-cell-centric modalities. Significance: This study uncovers that targeting dysregulated iron accumulation in ovarian tumors represents a major therapeutic opportunity. Iron chelation therapy using an FDA-approved agent causes immunogenic stress responses in ovarian cancer cells that delay metastatic disease progression and enhance the effects of first-line chemotherapy. See related commentary by Bell and Zou, p. 1771.

Iron Chelators and Alzheimer's Disease Clinical Trials.

Alzheimer's disease (AD) is a major neurodegenerative disorder impacting millions of people with cognitive impairment and affecting activities of daily living. The deposition of neurofibrillary tangles of hyperphosphorylated tau proteins and accumulation of amyloid-β (Aβ) are the main pathological characteristics of AD. However, the actual causal process of AD is not yet identified. Oxidative stress occurs prior to amyloid Aβ plaque formation and tau phosphorylation in AD. The role of master antioxidant, glutathione, and metal ions (e.g., iron) in AD are the frontline area of AD research. Iron overload in specific brain regions in AD is associated with the rate of cognitive decline. We have presented the outcome from various interventional trials involving iron chelators intended to minimize the iron overload in AD. To date, however, no significant positive outcomes have been reported using iron chelators in AD and warrant further research.

Deferasirox nanosuspension loaded dissolving microneedles for ocular drug delivery

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.

Invariant NKT (iNKT) cells are a group of innate-like T cells that plays important roles in immune homeostasis and activation. We found that iNKT cells, compared with CD4+ T cells, have significantly higher levels of lipid peroxidation in both mice and humans. Proteomic analysis also demonstrated that iNKT cells express higher levels of phospholipid hydroperoxidase glutathione peroxidase 4 (Gpx4), a major antioxidant enzyme that reduces lipid peroxidation and prevents ferroptosis. T cell-specific deletion of Gpx4 reduces iNKT cell population, most prominently the IFN-γ-producing NKT1 subset. RNA-sequencing analysis revealed that IFN-γ signaling, cell cycle regulation, and mitochondrial function are perturbed by Gpx4 deletion in iNKT cells. Consistently, we detected impaired cytokine production, elevated cell proliferation and cell death, and accumulation of lipid peroxides and mitochondrial reactive oxygen species in Gpx4 knockout iNKT cells. Ferroptosis inhibitors, iron chelators, vitamin E, and vitamin K2 can prevent ferroptosis induced by Gpx4 deficiency in iNKT cells and ameliorate the impaired function of iNKT cells due to Gpx4 inhibition. Last, vitamin E rescues iNKT cell population in Gpx4 knockout mice. Altogether, our findings reveal the critical role of Gpx4 in regulating iNKT cell homeostasis and function, through controlling lipid peroxidation and ferroptosis.

Identification of Isoliensinine as a Ferroptosis Suppressor with Iron-Chelating Activity.

Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of lipid peroxides. The high involvement of ferroptosis in diverse human diseases highlights the need for the identification of new chemotypes with anti-ferroptotic activity. Here, we performed a natural product library screening in HT1080 fibrosarcoma cells and identified licochalcone A (LA), isoeugenyl acetate (ISA), and isoliensinine (ISL) as suppressors of either RSL3- or IKE-induced ferroptosis. Mechanistically, ferroptosis resistance conferred by these compounds is mainly through GPX4/NRF2-independent mechanisms. Among them, only ISL could effectively rescue ferroptosis induced by FINO2, which is a stable oxidant of ferrous iron, suggesting that ISL may have the properties of an iron chelator. Consistent with the hypothesis, both computational tools and X-ray photoelectron spectroscopy supported the binding between ISL and iron ions. And ISL greatly inhibited excessive iron-dependent ferroptotic cell death through limiting intracellular iron accumulation. Furthermore, its iron chelator activity also protected mice from organ injury in an acute iron overload model. In conclusion, this study provided valuable insights for developing effective anti-ferroptosis agents from natural products, which represent a potential therapeutic strategy for treating ferroptosis-associated organ damage.

Iron chelation by oral deferoxamine treatment decreased brain iron and iron signaling proteins.

Deferoxamine (DFO) and other iron chelators are clinically used for cancer and stroke. They may also be useful for Alzheimers disease (AD) to diminish iron from microbleeds. DFO may also stimulate antioxidant membrane repair which is impaired during AD. DFO, and other chelators do enter the brain despite some contrary reports. Low dose, oral DFO was given in lab chow to wildtype (WT) C57BL/6 mice to evaluate potential impact on iron levels, iron-signaling and storage proteins, and amyloid precursor protein (APP) and processing enzymes. Young WT mice do not have microbleeds or disrupted blood-brain barrier of AD mice. Iron was measured by MRI and chemically after two weeks of dietary DFO. Cerebral cortex was examined for changes in iron metabolism, antioxidant signaling, and APP processing by Western blot. DFO decreased brain iron by 18% (MRI) and decreased seven major proteins that mediate iron metabolism by at least 25%. The iron storage proteins ferritin light and heavy chain decreased by at least 30%. APP and secretase enzymes also decreased by 30%. WT mice respond to DFO with decreased APP, amyloid processing enzymes, and antioxidant repair. Potential DFO treatment for early-stage AD by DFO should consider the benefits of lowered APP and secretase enzymes.

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells

The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

A COMPARATIVE STUDY OF EXTRACTION OPTIMIZATION, ANTIOXIDANT POTENTIAL, AND FATTY ACID COMPOSITION OF CUCUMI S ATIVUS AND CUCUMIS MELO

Background: Cucumis plants are being frequently used to treat metabolic disorders such as obesity and diabetes, in traditional medicinal system. Objectives: The current study sought to assess the impact of several solvents with varying polarity for the extraction of polyphenolic, and flavonoid components. Further, this study also aims to determine antioxidant activity of fruits and peels of Cucumis melo and Cucumis sativus. Methodology: Methanol, ethyl acetate, chloroform, and n-hexane were chosen for optimal extraction. Extract yields were assessed to determine the optimal solvent solution for extraction. The TPC and TFC contents were determined by Folin–Ciocalteu reagent and AlCl3 method. The antioxidant potential was determined spectrophotometrically using DPPH scavenging and iron chelation assays. The fatty acid contents of methanol extract were determined by gas chromatography (GC-FID). The instrument utilized for this purpose was a Shimadzu GC-14A with a flame ionizer (FID) and a packed glass column, DEXIL-300. The column oven's temperature was kept at 180ºC for 5 minutes and programmed to 250 ºC at the rate of 5ºC/mint. The injection and detector temperature was 250ºC and 230ºC respectively. Results: The results showed that the methanol extract of C. sativus peels exhibited the highest extraction yield, TPC, and TFC 12.72 ± 0.34 mg/mL, 130.13 ± 1.23 mg/mL, and 86.56 ± 0.67 mg/mL, respectively for C. Sativus peels and for C. melo the results were as 8.32. ± 0.34 mg/mL, 68.23.13 ± 1.23 mg/mL and 48.23 ± 0.67 mg/mL, respectively. The C. Sativus peel extract also showed the highest DPPH inhibition and iron chelation activities with IC50 values of 33.34 ± 0.12 µg/mL and 30.34 ± 0.23 µg/mL. The methanol extracts also showed dose-dependent antioxidant activities. The seven fatty acids contents were found from C12 to C20 in peel extract with arachidic acid and linoleic acid in relatively greater amounts. Conclusion: The current study has shown that the methanol extract of C. sativus peel has rich total phenolic, flavonoid content, and has reasonable antioxidant activity in all of the tested methods.

Coke oven emissions exacerbate allergic asthma by promoting ferroptosis in airway epithelial cells

Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.

Seed- and Foliar-Applied Iron Chelate Improves Performance, Physiological, and Biochemical Aspects of Black Cumin (Nigella sative) under Semi-Arid Conditions

The cultivation of medicinal plants plays a crucial role in promoting human health benefits. However, the production of these plants can be affected by drought conditions. This research aimed to investigate the impact of differing water status (non-drought and drought during the flowering to harvest stage) and various iron treatments on the performance of black cumin. The iron treatments included no iron as the control (nFe), no iron with seed hydro-priming (nFe + P), seed iron priming (pFe), seed iron priming with iron foliar spraying (pFe + sFe), and double iron foliar spraying (sFe + sFe). The purpose of these treatments was to assess the effect of iron application methods on plant response under different water conditions. The findings revealed that drought significantly reduced the levels of Chla (15%) and RWC (5.9%), plant height (7%), follicle number (16.7%), seed number (4.6%), 1000-seed weight (3.2%), and seed yield (30.1%). Additionally, drought increased the proline content (90.9%), electrolyte leakage (9.2%), and MDA levels (23.9%). Interestingly, applying iron amendments reduced electrolyte leakage and increased seed yield under both water conditions. The drought-induced increase in proline content was more pronounced in the nFe treatment than in the other treatments. The amount of MDA in the nFe and nFe + P treatments was significantly higher under drought conditions compared to non-drought conditions. In conclusion, the addition of iron amendments helps black cumin plants recover from the effects of drought and reduces damage to seed growth. This means that using both seed iron priming and iron foliar spraying can significantly improve yields. Alternatively, focusing on either seed iron priming or double iron foliar spraying can also boost black cumin production compared to not using iron amendments.

Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH

The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.

The Diagnostic Performance of Serum Glycosylated Ferritin in Patients Undergoing Regular Blood Transfusion: An Indicator of Iron Overload to Initiate Iron Chelation Therapy.

Background and objective Serum ferritin concentration and transferrin saturation are commonly employed to estimate body iron but are non-specific to iron overload. Glycosylated ferritin may be primarily elevated in cases of iron overload in patients undergoing regular blood transfusions. In this study, we aimed to estimate glycosylated ferritin and determine its cutoff values for iron overload in patients receiving blood transfusions regularly. We also endeavored to the examine correlation between serum ferritin and glycosylated ferritin in patients receiving regular blood transfusions. Methods We conducted a cross-sectional study involving 17 patients undergoing regular blood transfusions in the Department of Medical Oncology/Hematology, who had already received ≥10 transfusions without any iron chelation therapy or acute inflammation. All participants were evaluated based on a questionnaire to gather relevant medical details. Serum iron, ferritin, glycosylated ferritin, and unsaturated iron-binding capacity (UIBC) were estimated. Total iron-binding capacity (TIBC) and transferrin saturation were also calculated. Results Participants were divided into two groups based on transferrin saturation (≥50% as a reference for iron overload). The group with transferrin saturation ≥50% had significantly higher levels of serum ferritin, glycosylated ferritin, and iron, compared to the group with transferrin saturation <50%. Glycosylated ferritin showed a positive correlation with ferritin (rho=0.80) and transferrin saturation (rho=0.64), which was statistically significant. UIBCand TIBCshowed a negative association with glycosylated ferritin. The correlation of glycosylated ferritin with units of blood transfusion (Spearman's rho=0.60) was found to be better than that of serum ferritin (Spearman's rho=0.52). Conclusions Based on our findings, glycosylated ferritin could be a potential marker for transfusion-related iron overload. The optimal cutoff value for iron overload using serum glycosylated ferritin level was >587.55 ng/mL. Further extensive studies withlarger sample sizes will substantiate the role of glycosylated ferritin in predicting post-transfusion iron overload.

Unlocking the Siderophore Biosynthesis Pathway and Its Biological Functions in the Fungal Insect Pathogen Beauveria bassiana.

Siderophores are small molecule iron chelators. The entomopathogenic fungus Beauveria bassiana produces a plethora of siderophores under iron-limiting conditions. In this study, a siderophore biosynthesis pathway, akin to the general pathway observed in filamentous fungi, was revealed in B. bassiana. Among the siderophore biosynthesis genes (SID), BbSidA was required for the production of most siderophores, and the SidC and SidD biosynthesis gene clusters were indispensable for the production of ferricrocin and fusarinine C, respectively. Biosynthesis genes play various roles in siderophore production, vegetative growth, stress resistance, development, and virulence, in which BbSidA plays the most important role. Accordingly, B. bassiana employs a cocktail of siderophores for iron metabolism, which is essential for fungal physiology and host interactions. This study provides the initial network for the genetic modification of siderophore biosynthesis, which not only aims to improve the efficacy of biocontrol agents but also ensures the efficient production of siderophores.

Exploring the bone marrow micro environment in thalassemia patients: potential therapeutic alternatives.

Genetic mutations in the β-globin gene lead to a decrease or removal of the β-globin chain, causing the build-up of unstable alpha-hemoglobin. This condition is referred to as beta-thalassemia (BT). The present treatment strategies primarily target the correction of defective erythropoiesis, with a particular emphasis on gene therapy and hematopoietic stem cell transplantation. However, the presence of inefficient erythropoiesis in BT bone marrow (BM) is likely to disturb the previously functioning BM microenvironment. This includes accumulation of various macromolecules, damage to hematopoietic function, destruction of bone cell production and damage to osteoblast(OBs), and so on. In addition, the changes of BT BM microenvironment may have a certain correlation with the occurrence of hematological malignancies. Correction of the microenvironment can be achieved through treatments such as iron chelation, antioxidants, hypoglycemia, and biologics. Hence, This review describes damage in the BT BM microenvironment and some potential remedies.

Evaluation of anti-diabetic, anti-oxidant and anti-bacterial activities of essential oil collected from wildly growing Calotropis gigantea (Linn.) Aiton f. and its therapeutic applications: insights from chemical profiling, in-vitro and in-silico studies

Calotropis gigantea, often known as giant milkweed, the plant is widely known for producing herbal essential oils that are used as traditional and complementary medicine to cure various ailments. The aim of the present study was evaluation of anti-diabetic, anti-oxidant and anti-bacterial activities of essential oil collected from wildly growing Calotropis gigantea and its its therapeutic applications via chemical profiling, in-vitro and in-silico studies. After Calotropis gigantea (CEO) essential oil was extracted by hydro-distillation, its phytochemical, antioxidant, antibacterial, and anti-diabetic properties were assessed. Fingerprint analysis and GC-FID were used to create a chemical profile. Various tests for antioxidants, such as DPPH, nitric oxide radical, and iron chelating activity, were conducted. The disk diffusion approach was used for antibacterial efficacy against Gram-negative (G-) bacteria. The test of α-amylase inhibition was utilized to investigate anti-diabetic efficacy. In-silico analysis was also conducted to find out interaction of some components to α-amylase enzyme. Chemical profiling indicated the presence of phytol (24%), stearic acid (10%), and cyclohexyl ketone (6%), as predominant components. There was notable antioxidant activity ranged from 82 to 97% for various assays. IC50 values for various assays were iron chelating activity: 18.610, DPPH scavenging activity: 28.246, nitric oxide radical scavenging activity: 58.113. CEO showed a zone of inhibition value of 0.5 cm and significant antibacterial activity against Gram-negative (G-) bacteria. CEO blocked α-amylase in dose-dependent way. At a higher amount of 250 µl, CEO inhibition was 63% and mode of inhibition un-competitive. In-silico analysis validated the blocking of α-amylase and interaction of phytocomponents to α-amylase enzyme which were further validated by UV and fluorescent quenching techniques. It was determined that CEO may be extensively used in many different industries, including as food, herbal medicine, cosmetics.

Investigation of Chemical Composition, Antioxidant Properties, and Molecular Docking in Different Roasting Stages of Coffee Beans

AbstractThis study investigates the chemical composition and antioxidant properties of coffee beans at different roasting stages, namely green coffee, filter-roasted coffee, and espresso-roasted coffee. Using a Golden Roaster machine, specific roasting profiles were developed to achieve distinct flavor characteristics: an intense flavor and balanced acidity for espresso, and a balanced, complex taste for filter coffee. Results indicate that filter-roasted coffee exhibits the highest radical scavenging activity, as evidenced by its lowest IC50 value for 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Green coffee demonstrates superior iron chelation activity, while filter-roasted coffee contains the highest flavonol content and espresso-roasted coffee has the highest flavonoid content. Bacterial sensitivity tests show that both filter-roasted and espresso-roasted coffee are effective against certain strains, including Klebsiella pneumoniae ATCC 13883. Gas chromatography-mass spectrometry (GC–MS) analysis identifies key compounds such as caffeine and 4,4-dimethyl-3-(3-methylbut-3-enylidene)-2-methylenebicyclo [4.1.0] heptane in filter-roasted coffee, and 2-(2-hydroxyphenyl) buta-1,3-diene in espresso-roasted coffee. Molecular docking and in silico molecule’s absorption, distribution, metabolism, excretion, and toxicity (ADME) studies suggest potential pharmaceutical applications for coffee compounds. These findings provide valuable insights into coffee’s complex chemistry and its health-related properties. Additionally, the importance of coffee profiling in bioprocesses is highlighted by the need to carefully analyze the profiling process to optimize the biological effects and health benefits of these compounds. Coffee profiling not only enhances consumer taste experiences but also contributes to a better understanding of coffee’s potential health benefits by effectively identifying biomolecules and nutrients for use in bioprocesses. Graphical Abstract

Skin complications during iron chelation therapy for beta-thalassemia: overview and treatment approach.

Thalassemia is an inherited genetic disorder of hemoglobin that affects a large population worldwide, and it is estimated that between 50,000 and 60,000 infants with thalassemia are born each year. The most common treatment for thalassemia is blood transfusion, which leads to iron overload. This in itself is a serious clinical condition, and is commonly managed with iron chelation therapy. However, iron chelators can cause various skin complications, including hyperpigmentation, skin rash, itching, and photosensitivity. These skin side effects can impact patients' quality of life. Therefore, this article provides a comprehensive overview of skin complications caused by iron chelators, along with a proposed comprehensive approach to their management in patients with beta-thalassemia. Key strategies include patient education, regular skin assessment, sun protection measures, symptomatic relief with topical corticosteroids and antihistamines, and consideration of treatment modification if severe complications occur. Collaboration between hematologists and dermatologists, along with psychological support and regular follow-up, is an essential component of this multidisciplinary approach. By implementing these strategies, healthcare providers can optimize skin care for patients with beta-thalassemia treated with iron chelators and improve their quality of life.

Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives.

As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. Pub- Med/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein's clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.

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 β-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 β-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.