Search Results (1,731)

Background and Clinical Significance: Obstructive sleep apnea (OSA) is a common comorbidity in patients with cardiac and metabolic disorders. The coexistence of central sleep apnea with Cheyne–Stokes breathing (CSA-CSB) in heart failure patients, especially those with preserved ejection fraction (HFpEF), represents a diagnostic and therapeutic challenge. Data on continuous positive airway pressure (CPAP) failure and successful adaptation to servo-ventilation (ASV) in the context of complex comorbidities remain limited. Case Presentation: We present the case of a 74-year-old male with a history of type 2 diabetes mellitus, paroxysmal atrial fibrillation, HFpEF, essential hypertension, and bladder carcinoma. He was referred for pre-operative OSA screening, reporting excessive daytime sleepiness, insomnia, and witnessed apneas. Initial respiratory polygraphy revealed severe sleep-disordered breathing with dominant CSA-CSB and moderate OSA. Laboratory investigations also revealed severe iron-deficiency anemia, which was managed with parenteral iron supplementation. The patient underwent CPAP titration, which led to modest improvement and residual high apnea–hypopnea index (AHI). After persistent symptoms and an inadequate CPAP response, an ASV device was initiated with significant clinical and respiratory improvement, demonstrating normalization of hypoxic burden and optimal adherence. Conclusions: CSA-CSB in HFpEF patients with anemia poses unique therapeutic difficulties. This case highlights the importance of individualized diagnostic and therapeutic strategies, including transitioning to ASV in CPAP-refractory cases, which can lead to improved adherence, reduced hypoxia, and better overall outcomes in high-risk patients. 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

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint 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

Glutamate dehydrogenase (GDH) is ubiquitous in organisms and crucial for amino acid metabolism, energy production, and redox balance. The gdhA and gudB genes encoding GDH were identified in Bacillus altitudinis AS19 and shown to be regulated by iron. However, their functions remain unclear. In this study, gdhA and gudB were analyzed using bioinformatics tools, such as MEGA, Expasy, and SWISS-MODEL, expressed with a prokaryotic expression system, and the induction conditions were optimized to increase the yield of soluble proteins. Phylogenetic analysis revealed that GDH is evolutionarily conserved within the genus Bacillus. GdhA and GudB were identified as hydrophobic proteins, not secreted or membrane proteins. Their structures were primarily composed of irregular coils and α-helices. SWISS-MODEL predicts GdhA to be an NADP-specific GDH, whereas GudB is an NAD-specific GDH. SDS-PAGE analysis showed that GdhA was expressed as a soluble protein after induction with 0.2 mmol/L IPTG at 24 °C for 16 h. GudB was expressed as a soluble protein after induction with 0.1 mmol/L IPTG at 16 °C for 12 h. The proteins were confirmed by Western blot and mass spectrometry. The enzyme activity of recombinant GdhA was 62.7 U/mg with NADPH as the coenzyme. This study provides a foundation for uncovering the functions of two GDHs of B. altitudinis AS19. 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

Snails at hydrothermal vents rely on symbiotic bacteria for nutrition; however, the specifics of these associations in adapting to such extreme environments remain underexplored. This study investigated the community structure and metabolic potential of bacteria associated with two Indian Ocean vent snails, Chrysomallon squamiferum and Gigantopelta aegis. Using microscopic, phylogenetic, and metagenomic analyses, this study examines bacterial communities inhabiting the foot and gland tissues of these snails. G. aegis exhibited exceptionally low bacterial diversity (Shannon index 0.14–0.18), primarily Gammaproteobacteria (99.9%), including chemosynthetic sulfur-oxidizing Chromatiales using Calvin–Benson–Bassham cycle and methane-oxidizing Methylococcales in the glands. C. squamiferum hosted significantly more diverse symbionts (Shannon indices 1.32–4.60). Its black variety scales were dominated by Campylobacterota (67.01–80.98%), such as Sulfurovum, which perform sulfur/hydrogen oxidation via the reductive tricarboxylic acid cycle, with both Campylobacterota and Gammaproteobacteria prevalent in the glands. The white-scaled variety of C. squamiferum had less Campylobacterota but a higher diversity of heterotrophic bacteria, including Delta-/Alpha-Proteobacteria, Bacteroidetes, and Firmicutes (classified as Desulfobacterota, Pseudomomonadota, Bacteroidota, and Bacillota in GTDB taxonomy). In C. squamiferum, Gammaproteobacteria, including Chromatiales, Thiotrichales, and a novel order “Endothiobacterales,” were chemosynthetic, capable of oxidizing sulfur, hydrogen, or iron, and utilizing the Calvin–Benson–Bassham cycle for carbon fixation. Heterotrophic Delta- and Alpha-Proteobacteria, Bacteroidetes, and Firmicutes potentially utilize organic matter from protein, starch, collagen, amino acids, thereby contributing to the holobiont community and host nutrition accessibility. The results indicate that host species and intra-species variation, rather than the immediate habitat, might shape the symbiotic microbial communities, crucial for the snails’ adaptation to vent ecosystems. 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

Molasses, a by-product of raw sugar production, is widely used as a cost-effective carbon and nutrient source for industrial fermentations, including the production of baker’s yeast (Saccharomyces cerevisiae). Due to the cost and limited availability of molasses, efforts have been made to replace molasses with cheaper and more readily available substrates such as corn syrup. However, the quality of dry yeast drops following the replacement of molasses with corn syrup, despite the same amount of total sugar being provided. Our understanding of how molasses replacement affects yeast physiology, especially during the dehydration step, is limited. Here, we examined changes in gene expression of a strain of baker’s yeast during fermentation with increasing corn syrup to molasses ratios at the transcriptomic level. Our findings revealed that the limited availability of the key metal ions copper, iron, and zinc, as well as sulfur from corn syrup (i) reduced their intracellular storage, (ii) impaired the synthesis of unsaturated fatty acids and ergosterol, as evidenced by the decreasing proportions of these important membrane components with higher proportions of corn syrup, and (iii) inactivated oxidative stress response enzymes. Taken together, the molecular and metabolic changes observed suggest a potential reduction in nutrient reserves for fermentation and a possible compromise in cell viability during the drying process, which may ultimately impact the quality of the final dry yeast product. These findings emphasize the importance of precise nutrient supplementation when substituting molasses with cheaper substrates. Full article

The increasing threat of antimicrobial resistance (AMR), along with the limited availability of new lead compounds in the drug development pipeline, highlights the urgent need to discover antimicrobial agents with innovative mechanisms of action. In this regard, metal complexes offer a unique opportunity to access mechanisms distinct from those of conventional antibiotics. Although iron (Fe) is an essential element for all forms of life, including pathogenic bacteria, it also poses a serious risk of cytotoxicity due to its redox activity, which can trigger the production of reactive oxygen species (ROS) via the Fenton reaction. This review highlights recent advances in the development of iron-based antimicrobial agents that harness the toxicity resulting from dysregulated iron uptake, thereby inducing bacterial cell death through oxidative stress. These findings may guide the development of effective treatments for pathogenic infections and offer new perspectives on leveraging redox chemistry of iron to combat the growing threat of global bacterial resistance. Full article

Background/Objectives: This study aimed to investigate the association between serum ferritin levels and functional impairment in children with Attention Deficit Hyperactivity Disorder (ADHD). In addition, we investigated whether this relationship remained significant after controlling for core symptom severity and examined the correlations between ferritin levels and ADHD symptom levels. Methods: The sample included 88 children aged 6–13 years: 44 diagnosed with ADHD and 44 healthy controls (HCs) matched for age and sex. ADHD symptom severity was assessed using Turgay’s DSM-IV-Based ADHD and Disruptive Behavior Disorders Screening Scale (T-DSM-IV-S; parent-report) and the Clinical Global Impression—Severity (CGI-S) scale (clinician-rated). Functional impairment was measured using the Weiss Functional Impairment Rating Scale—Parent Report (WFIRS-P). Serum ferritin levels were determined through venous blood samples. Statistical analyses included group comparisons, Spearman correlations, and partial correlations controlling for symptom severity. Results: Children with ADHD had significantly lower serum ferritin levels and higher levels of both symptom severity and functional impairment compared to HCs. Ferritin levels were negatively correlated with ADHD symptom severity and with functional impairment in the Life Skills domain. However, after controlling for ADHD symptom severity, the association with Life Skills was no longer statistically significant. Conclusions: Ferritin levels were found to be associated with both ADHD symptom severity and functional impairment in the Life Skills domain. However, this relationship was not independent of symptom severity, suggesting that core ADHD symptoms may mediate the impact of iron status on daily functioning. Due to the study’s limitations (e.g., cross-sectional design, small sample size, gender imbalance, and lack of inflammatory and dietary data), our findings should be interpreted with caution, as they do not establish causality or resolve the ongoing inconsistencies in the literature. These results underscore the relevance of iron metabolism in the clinical presentation of ADHD and highlight the need for future research to determine whether improving iron status could serve as an adjunctive strategy in the management of functional impairments in this population. Full article

Micronutrient deficiencies adversely affect human health and pose a significant global threat. Enhancing the accumulation of micronutrients in the edible parts of crops through genetic breeding is a promising strategy to mitigate micronutrient deficiencies in humans. FW2.2-like (FWL) genes play crucial roles in regulating heavy metal homeostasis in plants. We previously obtained two allelic mutants for each of the rice OsFWL1 (osfwl1a and osfwl1b) and OsFWL2 (osfwl2a and osfwl2b) genes. In this study, we showed that disruption of either OsFWL1 or OsFWL2 significantly enhanced the accumulation of metallic micronutrients in brown rice. Compared with that in the wild type, the iron (Fe) concentration in brown rice was higher in the osfwl1a (+166.7%), osfwl1b (+24.3%), and osfwl2a (+99.2%) mutants; the manganese (Mn) concentration was elevated in all four mutants (+25.1% to 35.6%); the copper (Cu) concentration increased in osfwl2a (+31.0%) and osfwl2b (+29.0%); and the zinc (Zn) concentration increased in osfwl2a (+10.2%). Additionally, disruption of OsFWL1 or OsFWL2 affected the homeostasis of metallic micronutrients in seedlings. Transcriptome analysis suggested that OsFWL1 and OsFWL2 might regulate cell wall polysaccharide metabolism and the expression of heavy metal transporter genes. Protein interaction analysis revealed that OsFWL1 interacted with OsFWL2 on the cell membrane. These findings suggest that OsFWL1 and OsFWL2 can serve as genetic biofortification tools to increase the concentrations of metallic micronutrients in rice grains. Full article