Early detection of myocardial iron overload in patients with ß-thalassemia major using cardiac magnetic resonance T1 mapping.

BACKGROUND: The T2* technique, used for quantifying myocardial iron content (MIC), has limitations in detecting early myocardial iron overload (MIO). The in vivo mapping of the myocardial T1 relaxation time is a promising alternative for the early detection and management of MIO. METHODS: 32 ß-thalassemia major (ßTM) patients aged 11.5 ± 4 years and 32 healthy controls were recruited and underwent thorough clinical and laboratory assessments. The mid-level septal iron overload was measured through T1 mapping using a modified Look-Locker inversion recovery sequence with a 3 (3 s) 3 (3 s) 5 scheme. Septum was divided at the mentioned level into 3 zones corresponding to segments 8 and 9 in the cardiac segmentation model. RESULTS: 21.9 % of ßTM had clinical cardiac morbidity. The cut-off of T1 mapping of hepatic and myocardium to differentiate between the patients and control groups was ≤466 and ≥ 923 ms respectively. The T1 technique was able to detect 4 patients with high MIC, two of them were not detected by the T2* technique. There was a statistically significant correlation between the average T1 values of the studied zones in patients with ßTM and the liver iron content (LIC), the T1 values within segment 8 of the liver, age of patients, the age at first transfusion, age of splenectomy and serum ferritin value. CONCLUSION: The addition of the T1 mapping sequence to the conventional T2* technique was able to increase the efficacy of the MIC detection protocol by earlier detection of MIO. This would guide chelation therapy to decrease myocardial morbidity.

Speckle-tracking echocardiography as screening tool for myocardial fibrosis and Iron overload in transfusion-dependent beta-thalassemia.

BACKGROUND: Transfusion-dependent beta thalassemia (TDT) is a genetic disorder characterized by low haemoglobin levels, often leading to myocardial iron overload (MIO) and myocardial fibrosis (MF). Cardiac Magnetic Resonance (CMR) represents the gold standard for MIO and MF assessment, although its limited availability and high costs pose challenges. Left Ventricular Global Longitudinal Strain (LV GLS) measured by Speckle Tracking Echocardiography (STE) could offer a valuable alternative. METHODS: A monocentric diagnostic accuracy study was conducted to compare the performance of LV GLS with CMR using T2* for evaluating MIO and late gadolinium enhancement (LGE) for detecting MF. Between January 2022 and January 2023, 44 consecutive patients with TDT were enrolled. For each participant was performed LV GLS with STE, including CMR with T2* technique and LGE sequences. RESULTS: CMR identified MIO in 8 patients (18 %) and MF in 5 (11 %). LV GLS STE was normal in patients without MIO (-20.6 ±â€¯3.1 %) or MF (-20.6 ±â€¯2.8 %), significantly differing from those with MIO (-18.2 ±â€¯2.1 %, p = 0.043) and MF (-16.4 ±â€¯1.7 %, p = 0.002). ROC analysis indicated an optimal LV GLS STE cutoff of -19.8 % for MIO (AUC = 0.76, 95 % CI: 0.59-0.93, p = 0.054) with an overall diagnostic accuracy of 64 % and an optimal cutoff of -18.3 % for MF (AUC = 0.93, 95 % CI: 0.85-1.00, p = 0.009) with an accuracy of 86 %. CONCLUSIONS: The findings of this pilot study indicate that LV GLS with STE, may be a cost-effective screening tool for the early detection of MIO and MF in TDT patients.

[Hepatic iron overload]. / Les surcharges hépatiques en fer.

Iron is essential for functioning of cells and of the body as a whole. Perls staining allows the histopathological identification of iron deposits. By classifying hepatic siderosis as parenchymal, mesenchymal or mixed, it may guide the search for its etiology. HFE1 hemochromatosis is the most common siderosis. Its diagnosis is currently based on genetic analysis. Its expressivity being variable and its penetrance incomplete, the demonstration of hepatic siderosis may represent a mode of discovery.

Assessing the accuracy of CMRtools software for diagnosing liver iron overload in thalassemia patients: influencing factors and optimisation strategies.

Background: CMRtools is a software package that can be used to measure T2* values to diagnose liver iron overload, however, its accuracy in terms is affected by multiple factors, including goodness-of-fit (R2 value), the number of echo time (TE) images, and the liver iron concentration (LIC). To investigate the effects of the R2 value, the number of TE images, and the LIC on the accuracy of CMRtools software for measuring T2* values to diagnose liver iron overload (LIO). Materials and methods: CMRtools software was used to measure liver T2* values among 108 thalassemia patients via the truncation method, and the R2 values, the number of TE images, and T2* values were recorded. These values were subsequently converted into liver iron concentration (LICT) values. The LICF (derived from MRI-R2/FerriScan) was used as a reference, and the diagnostic accordance rate (DAR) was compared between R2 value subgroups, between TE image number subgroups, and between LIC subgroups. Results: The greater the R2 value was, the greater the standardized DAR (SDAR) was (p < 0.05). The SDAR are not identical between each TE image number subgroup (p > 0.05). However, the relationship between TE image number subgroups and SDAR was analysed using Spearman's correlation, and it was found to be positively correlated (rs = 0.729, p = 0.017). The SDAR are not identical between each LIC subgroup (p > 0.05), furthermore, the relationship between LIC subgroup and SDAR was found irrelevant (p = 0.747). Conclusion: The accuracy of CMRtools software for diagnosing LIO in patients with thalassemia can be improved by artificially controlling the number of TE images to be fitted and selecting higher R2 values.

Bone turnover, areal BMD, and bone microarchitecture by second-generation high-resolution peripheral quantitative computed tomography in transfusion-dependent thalassemia.

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and ß-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker ß-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ -2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2-86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96-2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia.

Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage.

Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown to upregulate FTMT. However, the effects of FTMT upregulation by Deferiprone on neuronal ferroptosis after GMH and its underlying mechanism has not been investigated. In our study, 389 Sprague-Dawley rat pups of postnatal day 7 were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. The brain expressions of FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) and acyl-CoA synthase long-chain family member 4 (ACSL4) were increased after GMH. FTMT agonist Deferiprone improved neurological deficits and hydrocephalus after GMH. Deferiprone or Adenovirus-FTMT enhanced YAP phosphorylation at the Ser127 site and attenuated ferroptosis, which was reversed by NDRG1 CRISPR Knockout. Iron overload induced neuronal ferroptosis and neurological deficits, which were improved by YAP CRISPR Knockout. Collectively, FTMT upregulation by Deferiprone reduced neuronal ferroptosis and neurological deficits via the NDRG1/YAP signaling pathway after GMH. Deferiprone may serve as a potential non-invasive treatment for GMH patients.

How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency.

BACKGROUND: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder. METHODS: A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases. RESULTS: Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the PKLR gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the PKLR gene when making therapeutic decisions about starting a patient on mitapivat. CONCLUSIONS: While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat.

Role of ferroptosis in the pathogenesis of heart disease.

Ferroptosis is a new form of regulated necrosis characterized by iron-dependent lipid peroxidation, leading to irreparable lipid damage, membrane permeabilization, and necrotic cell death. Ferroptosis has recently been implicated in the pathogenesis of multiple forms of heart disease such as myocardial infarction, cardiac hypertrophy, heart failure, and various cardiomyopathies. Important progress has also been made regarding how ferroptosis is regulated in vitro and in vivo as well as its role in cardiac homeostasis and disease pathogenesis. In this review, we discuss molecular mechanisms that regulates ferroptosis in the heart, including pathways leading to iron overload and lipid peroxidation as well as the roles of key organelles in this process. We also discuss recent findings pertaining to the new pathogenic role of ferroptosis in various forms of heart disease as well as genetic and pharmacologic strategies targeting ferroptosis in the heart.

Dysregulated S100A9 Expression Impairs Matrix Deposition in Chronic Wounds.

Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds.

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. UIBC and TIBC showed 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 with larger sample sizes will substantiate the role of glycosylated ferritin in predicting post-transfusion iron overload.

IL-6 signaling accelerates iron overload by upregulating DMT1 in endothelial cells to promote aortic dissection.

Aortic dissection (AD), caused by tearing of the intima and avulsion of the aortic media, is a severe threat to patient life and organ function. Iron is closely related to dissection formation and organ injury, but the mechanism of iron ion transport disorder in endothelial cells (ECs) remains unclear. We identified the characteristic EC of dissection with iron overload by single-cell RNA sequencing data. After intersecting iron homeostasis and differentially expressed genes, it was found that hypoxia-inducible factor-1α (HIF-1α) and divalent metal transporter 1 (DMT1) are key genes for iron ion disorder. Subsequently, IL-6R was identified as an essential reason for the JAK-STAT activation, a classical iron regulation pathway, through further intersection and validation. In in vivo and in vitro, both high IL-6 receptor expression and elevated IL-6 levels promote JAK1-STAT3 phosphorylation, leading to increased HIF-1α protein levels. Elevated HIF-1α binds explicitly to the 5'-UTR sequence of the DMT1 gene and transcriptionally promotes DMT1 expression, thereby increasing Fe2+ accumulation and endoplasmic reticulum stress (ERS). Blocking IL-6R and free iron with deferoxamine and tocilizumab significantly prolonged survival and reduced aortic and organ damage in dissection mice. A comparison of perioperative data between AD patients and others revealed that high free iron, IL-6, and ERS levels are characteristics of AD patients and are correlated with prognosis. In conclusion, activated IL-6/JAK1/STAT3 signaling axis up-regulates DMT1 expression by increasing HIF-1α, thereby increasing intracellular Fe2+ accumulation and tissue injury, which suggests a potential therapeutic target for AD.

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review.

Background and Aims: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD. Methods: A comprehensive search was conducted across five databases, leading to the selection of 18 papers for in-depth analysis. These studies collectively involved 381 PD patients, 60.3% were males. Results: No consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron-chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients. Conclusion: While iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis-stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention.

The effect of iron status on gadolinium deposition in the rat brain: mechanistic implications.

Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6 ppm, 6 ppt (20 g/kg Fe carbonyl) or 48 ppm for 3 weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10 mmol/kg dose of gadodiamide intravenously over 2 weeks, then left to washout gadodiamide for 3 days or 3 weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.

Emoxypine succinate modulates behavioral and molecular responses in zebrafish model of iron Overload-Induced neuroinflammation via CDK5/GSK3- ß and NLRP3 inflammasome pathway.

Excessive iron accumulation in the brain plays a significant role in neurodegenerative processes, contributing to the pathogenesis of Alzheimer's disease (AD). AD, a prominent neurological disorder affecting the central nervous system, is characterized by the accumulation of beta-amyloid (Aß) and tau phosphorylation. This accumulation leads to the subsequent development of cognitive impairments, particularly in learning and memory functions. This study investigates the neuroprotective effects of emoxypine succinate in a zebrafish model of iron overload-induced neurodegeneration. Iron was administered to the zebrafish for 28 days to induce neurodegeneration. Following induction, Emoxypine succinate was employed as a treatment intervention for 14 days (concentrations of 4 mg/L, 8 mg/L, and 12 mg/L). Following the end of the treatment, behavioral tests (Y maze test, Novel tank test) were conducted on the zebrafish, and the biochemical (MDA, Catalase, SOD, GSH) and molecular parameters (AchE, Iron levels, IL-1ß, TNF-α, CDK-5, GSK-3ß, and NLRP3) of the zebrafish brain were also assessed. In the novel tank test, emoxypine succinate-treated groups exhibited significantly increased time in the upper zone (p < 0.001), higher distance travelled (p < 0.001), and shorter latency to the top (p < 0.001) compared to the negative control. Similarly, the Y-maze test revealed improved time in the novel arm (p < 0.001) and total distance travelled (p < 0.001) in treated groups versus the negative control. Assessment of oxidative stress parameters demonstrated significant reductions in oxidative stress in emoxypine succinate-treated groups. Furthermore, AChE activity decreased significantly (p < 0.001), and brain iron levels decreased substantially (p < 0.001) in treated groups, indicating positive therapeutic outcomes. Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1ß, TNF-α, CDK-5, GSK-3ß, and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation.

Cardamonin attenuates iron overload-induced osteoblast oxidative stress through the HIF-1α/ROS pathway.

BACKGROUND: Osteoporosis(OP) is a bone disease under research. Iron overload is a significant risk factor. Iron balance is crucial for bone metabolism and biochemical processes. When there is an excess of iron in the body, it tends to produce reactive oxygen species (ROS) which can cause oxidative damage to cells. The flavonoid compound, Cardamonin (CAR), possesses potent anti-inflammatory and anti-iron overload properties that can be beneficial in mitigating the risk of OP. PURPOSE: This study investigates the potential therapeutic interventions and underlying mechanisms of CAR for treating OP in individuals with iron overload. METHODS: The model of iron-overloaded mice was established by intraperitoneally injecting iron dextran(ID) into the mice. OP severity was evaluated with micro-CT and Hematoxylin-Eosin (HE) staining in vivo. In vitro, the iron-overloaded osteoblast model was induced by ferric ammonium citrate. Cell counting kit 8 assay to evaluate cell viability, Annexin V-FITC/PI assay to detect cell apoptosis. A range of cellular markers were detected, including the variation in mitochondrial membrane potential (MMP), levels of malondialdehyde (MDA), ROS, and lipid hydroperoxide (LPO). RESULTS: CAR can reverse bone loss in iron overload-induced OP mouse models in vivo. CAR attenuates the impairment of iron overload on the activity and apoptosis of MC3T3-E1 cells as well as the accumulation of ROS and LPO activation via HIF-1α/ROS pathways. CONCLUSION: CAR downregulating HIF-1α pathways prevents inhibition of iron overload-induced osteoblasts dysfunctional by attenuating ROS accumulation, reducing oxidative stress, promotes bone formation, and alleviates OP.

Nanoparticle-delivered quercetin exhibits enhanced efficacy in eliminating iron-overloaded senescent chondrocytes.

Aim: The therapeutic potential of senolytic drugs in osteoarthritis (OA) is poorly known. Quercetin, a senolytic agent exhibits promising potential to treat OA, having limited bioavailability. We investigated the effects of Quercetin-loaded nanoparticles (Q-NP) with enhanced bioavailability in human chondrocytes mimicking OA phenotype.Materials & methods: The C-20/A4 chondrocytes were exposed to ferric ammonium citrate to induce OA phenotype, followed by treatment with free Quercetin/Q-NP for 24 and 48-h. Q-NP were synthesized by nanoprecipitation method. Following treatment chondrocytes were assessed for drug cellular bioavailability, viability, cell cycle, apoptosis, oxidative stress and expression of key senescence markers.Results: Q-NP exhibited 120.1 ± 1.2 nm particle size, 81 ± 2.4% encapsulation efficiency, increased cellular bioavailability and selective apoptosis of senescent chondrocytes compared with free Quercetin. Q-NP treatment also induced oxidative stress and reduced the expressions of senescence markers, including TRB3, p16, p62 and p21 suggesting their ability to eliminate senescent cells. Last, Q-NP arrested the cell cycle in the sub-G0 phase, potentially creating a beneficial environment for tissue repair.Conclusion: Q-NP propose a promising delivery system for treating OA by eliminating senescent chondrocytes through apoptosis. Furthermore, their enhanced cellular bioavailability and capacity to modify cell cycle and senescent pathways warrant further investigations.

[Box: see text].

Hepatic Visualization on DXA Scan: An Ancilliary Finding.

Thalassemia major is a genetic haemoglobinopathy manifesting as severe anaemia, jaundice and hepatosplenomegaly. Due to altered iron metabolism and increased bone resorption it is associated with secondary osteoporosis manifested as decreased bone mineral density (BMD). Dual energy X-ray absorptiometry (DXA) is frequently performed for the diagnosis of secondary osteoporosis. Soft tissues are rarely visualized on DXA unless there is calcification involving those structures like nephro-, cholelithiasis or iatrogenic e.g. surgical clips. Hepatic iron deposition occurs in thalassemia due to repeated blood transfusions which leads to increased density of the liver resulting in visualization of liver on DXA scan. We present an interesting image of hepatic visualization on DXA performed for bone mineral density assessment in a patient with thalassemia major.

Glioblastoma mesenchymal subtype enhances antioxidant defence to reduce susceptibility to ferroptosis.

Glioblastoma (GBM) represents an aggressive brain tumor, characterized by intra- and inter-tumoral heterogeneity and therapy resistance, leading to unfavourable prognosis. An increasing number of studies pays attention on the regulation of ferroptosis, an iron-dependent cell death, as a strategy to reverse drug resistance in cancer. However, the debate on whether this strategy may have important implications for the treatment of GBM is still ongoing. In the present study, we used ferric ammonium citrate and erastin to evaluate ferroptosis induction effects on two human GBM cell lines, U-251 MG, with proneural characteristics, and T98-G, with a mesenchymal profile. The response to ferroptosis induction was markedly different between cell lines, indeed T98-G cells showed an enhanced antioxidant defence, with increased glutathione levels, as compared to U-251 MG cells. Moreover, using bioinformatic approaches and analysing publicly available datasets from patients' biopsies, we found that GBM with a mesenchymal phenotype showed an up-regulation of several genes involved in antioxidant mechanisms as compared to proneural subtype. Thus, our results suggest that GBM subtypes differently respond to ferroptosis induction, emphasizing the significance of further molecular studies on GBM to better discriminate between various tumor subtypes and progressively move towards personalized therapy.

A ferrous fluorescence lifetime response probe for monitoring changes in lipid droplets during ferroptosis and imaging in liver disease model.

Ferrous ions (Fe2⁺) accumulation and abnormal alterations in lipid droplets (LDs) are closely associated with ferroptosis. In the liver, excessive iron accumulation promotes oxidative stress and exacerbates lipid droplet accumulation, while the disruption of iron homeostasis may also affect the formation and size of lipid droplets, their increased number and size can exacerbate the severity of disease under fatty liver conditions. The leads to hepatocyte damage, further triggering liver inflammation, fibrosis, and ultimately resulting in cirrhosis and hepatocellular carcinoma. Therefore, real-time monitoring of iron ion and lipid droplet changes is crucial for assessing the severity of liver disease, disease progression, and understanding the mechanisms of ferroptosis. We have developed a fluorescent probe, NRFep, for real-time monitoring of iron ion fluctuations and visualization of lipid droplet changes in ferroptosis and liver disease models. NRFep is specific and sensitive to iron ions and exhibits excellent stability in both cells and animal models. In addition, NRFep can be used to monitor changes in iron ions and lipid droplets in mouse liver injury and fatty liver models. Through fluorescence lifetime imaging technology, NRFep can also study the dynamic changes of intracellular iron ion content. NRFep provides a powerful tool for studying ferroptosis and related diseases, and its unique dual-monitoring function opens up new possibilities for developing new diagnostic and therapeutic strategies.

Advances in Oral Exfoliative Cytology: From Cancer Diagnosis to Systemic Disease Detection.

Oral exfoliative cytology has emerged as a valuable tool in the early detection of oral cancer and other systemic diseases. This review comprehensively examines the current applications and recent advancements in oral exfoliative cytology techniques. We analyzed published literature from the past decade, focusing on methodological improvements, diagnostic accuracy, and emerging applications. Key findings include: (1) Enhanced cell collection and preparation methods have significantly improved sample quality and diagnostic reliability. (2) Integration of molecular markers and DNA analysis with traditional cytomorphological assessment has increased diagnostic sensitivity and specificity for oral cancer detection. (3) Novel applications in systemic disease detection, including diabetes and iron overload disorders, demonstrate the expanding utility of this technique. (4) Computer-assisted analysis and deep learning algorithms show promise in improving diagnostic accuracy and efficiency. Despite these advancements, challenges remain in standardization and widespread clinical implementation. This review provides a critical evaluation of oral exfoliative cytology's current status and future potential in oral and systemic disease diagnosis.