The aim of this study was to compare the aqueous humor (AH) and serum concentrations of metabolites in diabetic (n = 36) and nondiabetic (n = 36) senior adults undergoing cataract surgery. Blood ...samples were collected before surgery and AH during surgery. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted metabolomic and lipidomic analyses of samples were performed using the AbsoluteIDQ® p180 kit. Out of 188 metabolites targeted by the kit, 41 and 133 were detected in >80% of AH and serum samples, respectively. Statistical analysis performed to indicate metabolites differentiating diabetic and nondiabetic patients showed 8 and 20 significant metabolites in AH and serum, respectively. Pathway analysis performed for significant metabolites revealed that galactose metabolism is mostly affected in the AH, while arginine biosynthesis is mostly affected in the serum. Among metabolites that differentiate diabetic and nondiabetic patients, arginine was the only metabolite common to both serum and AH samples, as well as the only one with a decreased concentration in both body fluids of diabetic patients. Concentrations of the rest were elevated in AH and lowered in serum. This may suggest different mechanisms of diabetes-related dysregulation of the local metabolism in the eye in comparison to systemic changes observed in the blood.
Diabetes mellitus, a disease of modern civilization, is considered the major mainstay of mortalities around the globe. A great number of biochemical changes have been proposed to occur at metabolic ...levels between perturbed glucose, amino acid, and lipid metabolism to finally diagnoe diabetes mellitus. This window period, which varies from person to person, provides us with a unique opportunity for early detection, delaying, deferral and even prevention of diabetes. The early detection of hyperglycemia and dyslipidemia is based upon the detection and identification of biomarkers originating from perturbed glucose, amino acid, and lipid metabolism. The emerging “OMICS” technologies, such as metabolomics coupled with statistical and bioinformatics tools, proved to be quite useful to study changes in physiological and biochemical processes at the metabolic level prior to an eventual diagnosis of DM. Approximately 300–400 such metabolites have been reported in the literature and are considered as predicting or risk factor-reporting metabolic biomarkers for this metabolic disorder. Most of these metabolites belong to major classes of lipids, amino acids and glucose. Therefore, this review represents a snapshot of these perturbed plasma/serum/urinary metabolic biomarkers showing a significant correlation with the future onset of diabetes and providing a foundation for novel early diagnosis and monitoring the progress of metabolic syndrome at early symptomatic stages. As most metabolites also find their origin from gut microflora, metabolism and composition of gut microflora also vary between healthy and diabetic persons, so we also summarize the early changes in the gut microbiome which can be used for the early diagnosis of diabetes.
Extensive research has been conducted to gain a deeper understanding of the deregulated metabolic pathways in the development of trisomy 21 (T21) or Down syndrome. This research has shed light on the ...hypothesis that oxidative stress plays a significant role in the manifestation of the T21 phenotype. Although in vivo studies have shown promising results in mitigating the detrimental effects of oxidative stress, there is currently a lack of introduced antioxidant treatment options targeting cognitive impairments associated with T21. To address this gap, a comprehensive literature review was conducted to provide an updated overview of the involvement of oxidative stress in T21. The review aimed to summarize the insights into the pathogenesis of the Down syndrome phenotype and present the findings of recent innovative research that focuses on improving cognitive function in T21 through various antioxidant interventions. By examining the existing literature, this research seeks to provide a holistic understanding of the role oxidative stress plays in the development of T21 and to explore novel approaches that target multiple aspects of antioxidant intervention to improve cognitive function in individuals with Down syndrome.
Graphical Abstract
The guides -base systematic review process (Hutton et al.
2015
).
Congenital diaphragmatic hernia (CDH) represents a developmental anomaly that profoundly impacts the embryonic development of both the respiratory and cardiovascular systems. Understanding the ...influences of developmental defects, their origins, and clinical consequences is of paramount importance for further research and the advancement of therapeutic strategies for this condition. In recent years, groundbreaking studies in the fields of metabolomics and genomics have significantly expanded our knowledge regarding the pathogenic mechanisms of CDH. These investigations introduce novel diagnostic and therapeutic avenues. CDH implies a scarcity of available information within this domain. Consequently, a comprehensive literature review has been undertaken to synthesize existing data, providing invaluable insights into this rare disease. Improved comprehension of the molecular underpinnings of CDH has the potential to refine diagnostic precision and therapeutic interventions, thus potentially enhancing clinical outcomes for CDH patients. The identification of potential biomarkers assumes paramount significance for early disease detection and risk assessment in CDH, facilitating prompt recognition and the implementation of appropriate interventions. The process of translating research findings into clinical practice is significantly facilitated by an exhaustive literature review. It serves as a pivotal step, enabling the integration of novel, more effective diagnostic and therapeutic modalities into the management of CDH patients.
•Lung hypoplasia and pulmonary hypertension constitute the hallmark features of CDH.•MiRNAs may play a role in the pathogenesis of pulmonary vascular dysfunction in CDH.•MiRNAs may be possible early prenatal biomarkers of CDH.•Novel research on specific miRNAs or mitochondria as potential therapeutic targets
It is hypothesized that the oxidative stress level in thyroid cancer patients is additionally upregulated by radioactive iodine (RAI) treatment, that may exert an important impact on future health ...concerns. In our study, we evaluated the oxidative stress level changes using the measurement of malondialdehyde (MDA) concentration in patients with differentiated thyroid cancer (DTC) undergoing RAI treatment. Considering the results obtained in the study group, the serum levels of MDA in DTC patients were significantly higher compared to the healthy subjects (p < 0.05). The MDA concentration was significantly higher on the third day after RAI (p < 0.001) and significantly lower one year after RAI (p < 0.05) in DTC patients compared to the baseline concentration. Moreover, the redox stabilization after RAI treatment in patients with DTC during a year-long observation was demonstrated. Accordingly, an increased oxidative stress impact on the related biochemical parameters reflecting the health conditions of the DTC patients was determined. Our study showed that increased oxidative stress reflected by MDA measurements in DTC patients is further enhanced by RAI, but this effect is no longer observed one year after the therapy.
In physiological concentrations, reactive oxygen species play a vital role in regulating cell signaling and gene expression. Nevertheless, oxidative stress is implicated in the pathogenesis of ...numerous diseases and can inflict damage on diverse cell types and tissues. Thus, understanding the factors that mitigate the deleterious effects of oxidative stress is imperative for identifying new therapeutic targets. In light of the absence of direct treatment recommendations for reducing oxidative stress, there is a continuing need for fundamental research that utilizes innovative therapeutic approaches. Metformin, known for its multifaceted beneficial properties, is acknowledged for its ability to counteract the adverse effects of increased oxidative stress at both molecular and cellular levels. In this review, we delve into recent insights regarding metformin's antioxidant attributes, aiming to expand its clinical applicability. Our review proposes that metformin holds promise as a potential adjunctive therapy for various diseases, given its modulation of oxidative stress characteristics and regulation of diverse metabolic pathways. These pathways include lipid metabolism, hormone synthesis, and immunological responses, all of which may experience dysregulation in disease states, contributing to increased oxidative stress. Furthermore, our review introduces potential novel metformin-based interventions that may merit consideration in future research. Nevertheless, the necessity for clinical trials involving this drug remains imperative, as they are essential for establishing therapeutic dosages and addressing challenges associated with dose-dependent effects.
The molecular mechanism of action and the individual influence of various metabolic pathways related to metformin intervention are under current investigation. The available data suggest that ...metformin provides many advantages, exhibiting anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, otoprotective, radioprotective, and radio-sensitizing properties depending on cellular context. This literature review was undertaken to provide novel evidence concerning metformin intervention, with a particular emphasis on cancer treatment and prevention. Undoubtedly, the pleiotropic actions associated with metformin include inhibiting inflammatory processes, increasing antioxidant capacity, and improving glycemic and lipid metabolism. Consequently, these characteristics make metformin an attractive medicament to translate to human trials, the promising results of which were also summarized in this review.
Angioinvasion remains the important prognostic feature in papillary thyroid cancer (PTC) patients. Literature data indicates several markers that may be associated with oxidative stress and/or ...angioinvasion. Therefore, we assessed the utility of selected parameters in angioinvasion and metastasis screening in serum of PTC patients. Serum antioxidant capacity (TAC) and sirtuin 3 (SIRT3) levels were decreased (all p < 0.05) and both DNA/RNA oxidative stress damage products (DNA/RNA OSDP) and malondialdehyde (MDA) levels were increased in PTC patients with angioinvasion and metastasis (study group) when compared with PTC patients without these features (all p < 0.01). The highest screening utility in differentiation between angioinvasion and metastasis presence and absence in PTC patients was presented for DNA/RNA OSDP (AUC = 0.71), SIRT3 (AUC = 0.70), and TAC (AUC = 0.67) (all p < 0.05). Our study suggests that peripheral concentration of oxidative stress markers could be useful as angioinvasion and metastasis indicator in PTC patients.
Abstract
Aberrant metabolism has been identified as a main driver of cancer. Profiling of metabolism-related pathways in cancer furthers the understanding of tumor plasticity and identification of ...potential metabolic vulnerabilities. In this prospective controlled study, we established transcriptomic profiles of metabolism-related pathways in endometrial cancer (EC) using a novel method, NanoString nCounter Technology. Fifty-seven ECs and 30 normal endometrial specimens were studied using the NanoString Metabolic Panel, further validated by qRT-PCR with a very high similarity. Statistical analyses were by GraphPad PRISM and Weka software. The analysis identified 11 deregulated genes (FDR ≤ 0.05; |FC|≥ 1.5) in EC:
SLC7A11
;
SLC7A5
;
RUNX1
;
LAMA4
;
COL6A3
;
PDK1
;
CCNA1
;
ENO1
;
PKM
;
NR2F1
; and
NAALAD2
. Gene ontology showed direct association of these genes with ‘central carbon metabolism (CCM) in cancer’. Thus, ‘CCM in cancer’ appears to create one of the main metabolic axes in EC. Further, transcriptomic data were functionally validated with drug repurposing on three EC cell lines, with several drug candidates suggested. These results lay the foundation for personalized therapeutic strategies in this cancer. Metabolic plasticity represents a promising diagnostic and therapeutic option in EC.
Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and ...prognosis.
This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity (TOC), total antioxidant capacity (TAC), and sortilin), as potential indicators of angioinvasion in PTC.
A cross-sectional study involving 50 angioinvasive PTC patients (study group) and 30 PTC patients with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion.
Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context.
Participants included PTC patients, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded.
Serum biomarkers were measured to evaluate their association with PTC angioinvasion.
Primary outcome measures included serum levels of 8-OHdG, TOC, TAC, and sortilin.
Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, while TAC showed a notable decrease (all p < 0.01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high AUC value (0.963) for angioinvasion discernment.
Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results.
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