Search Results (432)

During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes—autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation—are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy–ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial–metabolic interactions. Full article

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

The search for the biomarkers of Alzheimer’s disease (AD) may prove essential in the diagnosis and prognosis of the pathology, and the differential expression of key proteins may assist in identifying new therapeutic targets. In this proof-of-concept (POC) study, a new approach of data mining and matching combined with the biochemical analysis of proteins was applied to AD investigation. Three influential online open databases (UniProt, AlzGene, and Allen Human Brain Atlas) were explored to identify the genes and encoded proteins involved in AD linked to mitochondrial and iron dysmetabolism. The databases were searched using specific keywords to collect information about protein composition, and function, and meta-analysis data about their correlation with AD. The extracted datasets were matched to yield a list of relevant proteins in AD. The biochemical analysis of their amino acid content suggested a defective synthesis of these proteins in poorly oxygenated brain tissue, supporting their relevance in AD progression. The result of our POC study revealed several potential new markers of AD that deserve further molecular and clinical investigation. This novel database search approach can be a valuable strategy for biomarker search that can be exploited in many diseases. Full article

Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article

(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress. Full article

Background: Acute leukemia (AL) is the most prevalent pediatric malignancy and is frequently associated with systemic iron dysregulation, often leading to iron overload. This study aimed to characterize the regulatory mechanisms of iron metabolism in children with AL, considering treatment stages and associated clinical parameters. Methods: A total of 149 children were stratified into four groups: newly diagnosed AL (n = 43), patients post-chemotherapy (n = 55), patients following hematopoietic cell transplantation (HCT; n = 32), and healthy controls (n = 19). Serum concentrations of matriptase-2 (TMPRSS6), neogenin-1 (NEO1), and soluble hemojuvelin (sHJV) were quantified using ELISA. Results: Compared to healthy children, significantly higher serum concentrations of TMPRSS6 and NEO1 were found in patients post-chemotherapy and post-HCT, while sHJV levels were markedly decreased. Higher TMPRSS6 and NEO1 levels and lower sHJV were associated with increased ferritin levels and greater numbers of transfused packed red blood cell (PRBC) units. sHJV negatively correlated with TMPRSS6, NEO1, ferritin, C-reactive protein (CRP), and PRBC transfusions. TMPRSS6 and NEO1 showed a positive correlation. Among the analyzed biomarkers, Kaplan–Meier analysis revealed no statistically significant associations with overall survival (OS) or event-free survival (EFS) within the chemotherapy and HCT subgroups. Conclusions: AL in pediatric patients is associated with profound disruptions of systemic iron homeostasis. Our investigation identified notable perturbations in TMPRSS6, NEO1, and sHJV, suggesting that these proteins could contribute mechanistically to the pathophysiological alterations underlying iron dysregulation observed in pediatric AL. Full article

Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article

Milk lactose concentration has been proposed as a noninvasive indicator of metabolic health in dairy cows, particularly during early lactation when metabolic demands are elevated. This study aimed to investigate the relationship between milk lactose levels and physiological, biochemical, and behavioral parameters in early-lactation Holstein cows. Twenty-eight clinically healthy cows were divided into two groups: Group 1 (milk lactose < 4.70%, n = 14) and Group 2 (milk lactose ≥ 4.70%, n = 14). Both groups were monitored over a 21-day period using the Brolis HerdLine in-line milk analyzer (Brolis Sensor Technology, Vilnius, Lithuania) and SmaXtec intraruminal boluses (SmaXtec Animal Care Technology^®, Graz, Austria). Parameters including milk yield, milk composition (lactose, fat, protein, and fat-to-protein ratio), blood biomarkers, and behavior were recorded. Cows with higher milk lactose concentrations (≥4.70%) produced significantly more milk (+12.76%) and showed increased water intake (+15.44%), as well as elevated levels of urea (+21.63%), alanine aminotransferase (ALT) (+22.96%), glucose (+4.75%), magnesium (+8.25%), and iron (+13.41%) compared to cows with lower lactose concentrations (<4.70%). A moderate positive correlation was found between milk lactose and urea levels (r = 0.429, p < 0.01), and low but significant correlations were observed with other indicators. These findings support the use of milk lactose concentration as a practical biomarker for assessing metabolic and physiological status in dairy cows, and highlight the value of integrating real-time monitoring technologies in precision livestock management. Full article

MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by using peripheral blood mononuclear cells (PBMCs) and serum-derived extracellular vesicles (EVs) as biological samples. We selected the known OS/IFM-associated microRNAs miR-146a-5p, miR-155-5p, and miR-21-5p as candidates for our GDM biomarker analysis. Quantitative RT-PCR was employed for relative quantification of the selected microRNAs from paired samples of PBMCs and EVs derived from patients with GDM and healthy controls (n = 50 per group). The expression levels were analyzed for correlations with lipid and glycemic status indicators; metal ion-related parameters; serum thiol content; protein carbonyl and thiobarbituric acid-reactive substances’ (TBARS) levels; glutathione reductase (GR), Superoxide dismutase (SOD), and catalase (CAT) activity; and NRF2 expression. MiR-146a-5p and miR-21-5p were significantly upregulated in both PBMCs and EVs obtained from GDM patients. EVs-miR-21-5p showed a positive correlation with glycemic status in GDM patients, while miR-155-5p from PBMCs demonstrated correlation with iron-related parameters. The expression of selected microRNAs was found to correlate with NRF2 expression and SOD activity. The level of miR-146a-5p negatively correlated with neonatal anthropometric characteristics, while a higher level of PBMCs-miR-21-5p expression was determined in GDM patients with adverse pregnancy outcomes (p = 0.012). Our data demonstrate a disturbance of OS/IFM-microRNAs in GDM and illustrate their potential to serve as indicators of the associated OS-related changes, neonatal characteristics, and adverse pregnancy outcomes. Full article

Introduction: Celiac disease (CD) impairs bone development in children through inflammation and nutrient malabsorption. Osteoprotegerin (OPG), a decoy receptor for RANKL, plays a role in bone remodeling and is increasingly recognized as a potential biomarker of bone metabolism and inflammation. However, its clinical significance in pediatric CD remains unclear. Aim: To evaluate the relationship between OPG levels, growth parameters, and delayed bone age in children with CD, and to assess OPG’s potential as a biomarker of bone health and disease activity. Methods: This three-year case–control study included 146 children: 25 with newly diagnosed CD (Group A), 54 with established CD on a gluten-free diet (Group B), and 67 healthy controls (Group C). Participants underwent clinical, anthropometric, and laboratory assessments at baseline and after 6 months (Groups A and B). OPG and osteocalcin were measured, and bone age was assessed radiologically. Statistical analyses included ANOVA, Spearman’s correlations, and binomial logistic regression. Results: OPG levels were highest in newly diagnosed children (Group A), showing a non-significant decrease after gluten-free diet initiation. OPG correlated negatively with age and height in CD patients and controls, and positively with hemoglobin and iron in Group B. Logistic regression revealed no significant predictive value of OPG for delayed bone age, although a trend was observed in Group B (p = 0.091). Children in long-term remission exhibited bone maturation patterns similar to healthy peers. Conclusions: OPG levels reflect disease activity and growth delay in pediatric CD but lack predictive power for delayed bone age. While OPG may serve as a secondary marker of bone turnover and inflammatory status, it is not suitable as a standalone biomarker for skeletal maturation. These findings highlight the need for integrative biomarker panels to guide bone health monitoring in children with CD. Full article

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has emerged as a pivotal mechanism in understanding the toxicological effects of various environmental pollutants. This short review delves into the intricate pathways of ferroptosis, its induction by diverse environmental toxicants, and the subsequent implications for human health. By elucidating and understanding pathways involved in environmental exposures and ferroptosis, we aim to shed light on potential therapeutic interventions and preventive strategies. Furthermore, identifications of biomarkers of ferroptosis will aid in monitoring ferroptosis-induced diseases/tissue damage, promoting the development of targeted therapies. Full article

Background/Objectives: Iron stores accrued in utero are critical for fetal and infant neurodevelopment. Low neonatal hemoglobin (Hb) may indicate inadequate iron capture and storage. Prior studies differ on whether and under what conditions maternal anemia predicts neonatal Hb; whether sex differences are present is unknown. Methods: Maternal and neonatal Hb and sociodemographic and health characteristics were abstracted from electronic medical records for biorepository participants at a tertiary academic medical center. Maternal anemia was defined as Hb < 11 g/dL in trimesters T1 and T3 and Hb < 10.5 g/dL in T2. Adjusted linear regression models were used to estimate associations of maternal anemia with neonatal Hb. Sex differences were evaluated with product terms and stratification. Results: In 228 participants with maternal Hb measured, the prevalence of prenatal (pre-delivery) and delivery anemia was 54% and 44%, respectively. Maternal race and ethnicity but no other sociodemographic characteristics were associated with maternal anemia. Neonatal hematology was available for 114 newborns < 7 days old (50%; 52% male). The median (IQR) neonatal Hb was 16.7 g/dL (14.9, 18.0) and did not differ by sex, but it was lower among infants of mothers with vs. without delivery anemia (15.9 vs. 17.1, p = 0.032) and those identifying as Black vs. Hispanic or other (16.0, 17.9, 17.0, respectively; p = 0.003). Independent associations of maternal anemia and race and ethnicity with neonatal Hb were stronger in males and attenuated to null in females. Conclusions: Maternal anemia was highly prevalent and associated sex-specifically with neonatal Hb independent of maternal race and ethnicity. Future studies to replicate these findings with a more comprehensive panel of iron biomarkers are needed. Functional consequences of greater susceptibility to risk factors for low neonatal Hb in male infants need to be further investigated. Full article

Background: This case–control study evaluated the concentrations of zinc (Zn), iron (Fe), and copper (Cu) in the aqueous humor (AH) of patients with primary glaucoma, and their relationships with clinical factors. Methods: This study enrolled 100 patients with primary glaucoma and categorized them into subtypes: acute angle-closure crisis (AACC), primary angle-closure glaucoma (PACG), and primary open-angle glaucoma (POAG). A total of 67 patients with senile cataract were enrolled as controls. Their AH samples and clinical information were obtained. Results: In primary glaucoma, Zn, Fe, and Cu concentrations increased, especially in AACC group; Zn, Fe, and Cu were positively correlated mutually; and decreased Zn/Fe and increased Fe/Cu were observed. The number of quadrants with closed anterior chamber angle on gonioscopy was positively associated with Fe and Cu levels in AACC and with Zn and Cu levels in PACG. In POAG, we found negative associations between Zn and the number of quadrants with retinal nerve fiber layer thinning on optical coherence tomography, Fe and age, and Cu and the cup-to-disc ratio. Trace metals showed high efficiency in discriminating primary glaucoma from controls. Conclusions: Zn, Fe, and Cu concentrations in patients with primary glaucoma increased and were associated with clinical factors, acting as potential biomarkers. Full article

Objectives: This study aimed to explore the mediating effects of iron homeostasis biomarkers linking central obesity with metabolic dysfunction-associated steatotic liver disease (MASLD) and primary liver cancer (PLC) via Mendelian randomization (MR) analysis. Methods: Two-sample bidirectional MR, multivariable MR, and mediation analyses were used to investigate the causal associations among obesity-related traits, iron homeostasis biomarkers, MASLD, and PLC. For the discovery and replication analyses, GWAS summary data for iron homeostasis biomarkers, MASLD, and PLC were extracted from two datasets, and the combined effects were pooled to corroborate the conclusions. Results: BMI and waist circumference were associated with a risk of MASLD in their combined effects (OR = 1.83, 95% CI = 1.33–2.52 for BMI; OR = 1.98, 95% CI = 1.63–2.41 for waist circumference). Waist circumference but not BMI had significant causal effects on the risk of PLC in the discovery dataset (OR = 1.71, 95% CI = 1.01–2.89 for BMI; OR = 2.72, 95% CI = 1.37–5.39 for waist circumference). In both of the iron homeostasis datasets, genetically predicted increased ferritin was associated with increased risk of MASLD by multivariable MR. We only observed that genetic liability to increased ferritin was associated with increased risk of PLC in iron homeostasis dataset 1 after adjusting for waist circumference. By two-step MR analysis, we found that genetic liability to ferritin mediated 3.34% (95% CI: 0.17–8.08%) of waist circumference effects on MASLD risk and 18.84% (95% CI: 3.01–40.51%) of its effects on PLC risk. Conclusions: Waist circumference and iron homeostasis biomarkers were causally associated with increased risks of MASLD and PLC. Central obesity may contribute to the development of MASLD and PLC by increasing ferritin levels. Full article

Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in blocking ferroptosis and is frequently upregulated in therapy-resistant HNC subtypes. In this review, we examine the multifaceted regulation of GPX4 expression and function, including transcriptional, post-transcriptional, epigenetic, and proteostatic mechanisms. We explore how GPX4 suppression through pharmacologic inhibitors (e.g., RSL3, withaferin A, statins), metabolic stress, or combined therapies (e.g., radiotherapy, EGFR inhibitors, immunotherapy) induces ferroptosis and resensitizes resistant tumors. We also summarize emerging biomarkers, including GPX4, ACSL4, SLC7A11, and NCOA4, that predict ferroptosis sensitivity and may guide patient selection for ferroptosis-targeted therapies. Single-cell and spatial transcriptomics reveal significant intratumoral heterogeneity in ferroptosis susceptibility, underscoring the need for precision approaches. Despite promising preclinical data, challenges such as drug delivery, toxicity, and resistance mechanisms remain. Nevertheless, the ferroptosis-GPX4 axis represents a unique vulnerability in HNC that can be therapeutically exploited. Integrating ferroptosis modulation into personalized oncology may transform outcomes for patients with refractory disease. Full article