Search Results (3,828)

Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC₅₀ was determined to be 0.03%. Embryos at 2 h post-fertilization (hpf) were exposed for 96 h to 0.0004% (LC₁₀) and 0.03% (LC₅₀). Exposure to 0.0004% caused no significant effects compared to controls. In contrast, exposure to 0.03% significantly increased mortality, reduced heart rate, impaired locomotion, and induced multiple malformations. Biochemical analyses revealed alterations in redox-associated biomarkers, characterized by unchanged ROS levels and mitochondrial activity, increased antioxidant enzyme activities (SOD, GPx, GR), and a decreased GSH:GSSG ratio. Lipid peroxidation levels were reduced, while a significant increase in DNA double-strand breaks (DSBs) was observed. Additionally, Nrf2 protein expression was upregulated at 0.03%. Together, these findings suggest concentration-dependent developmental toxicity correlated with alterations in redox homeostasis and genomic stability during early zebrafish development. This study provides new insight into the developmental hazard potential of a commercial Aloe vera extract in an aquatic vertebrate model. Full article

Oral squamous cell carcinoma (OSCC) typically develops in individuals with established risk factors such as tobacco and alcohol use, yet an increasing number of cases occur in young non-smoking, non-drinking (NSND) patients. We report a case of oral tongue OSCC in a 33-year-old woman who is a never-smoker and never-drinker without identifiable environmental or local risk factors. The patient underwent surgical treatment followed by adjuvant radiotherapy and remains disease-free 15 months after therapy. Whole-exome sequencing (WES) revealed a pathogenic truncating TP53 mutation together with additional somatic alterations affecting genes involved in DNA repair, hypoxia adaptation, mitochondrial function, and epigenetic regulation. The heterogeneous mutational profile suggests branched tumor evolution and the involvement of non-classical tumorigenic pathways. This report contributes to the growing evidence that OSCC in young NSND patients represents a biologically distinct subgroup and demonstrates the value of comprehensive genomic profiling for improving understanding of tumor heterogeneity and potential molecular drivers in the absence of traditional carcinogenic exposures. Full article

Cystic echinococcosis (CE) is caused by a tapeworm of the Echinococcus granulosus s.l. species complex belonging to the Taeniidae family. CE affects more than 100 countries, including Poland, while remaining a significant public health threat to both humans and livestock. The aim of this study was to identify the genotypes responsible for cases of cystic echinococcosis in Poland by conducting molecular analysis of larvae isolated from Polish patients, and to investigate the diagnostic pathways leading to CE diagnosis. Between April 2023 and January 2025, tissue samples were collected from 10 patients following hepatectomy. Analysis of diagnostic pathways revealed that radiological findings followed by PCR or histopathological testing were sufficient to establish a reliable diagnosis of CE in 90% and 100% of cases, respectively. Serological tests showed lower sensitivity, reaching 86% for ELISA and 71% for Western blot. DNA extracted from all samples was used as the template in PCR to amplify and sequence the region of the mitochondrial NADH dehydrogenase 1 gene (nad1). PCR analysis confirmed presence of Echinococcus granulosus s.l. species in eight cases. All obtained nad1 sequences showed identity with the Echinococcus canadensis G7 (pig) strain. These results indicate that it remains the most frequent causative agent of human cystic echinococcosis in Poland. Full article

Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article

Fanconi anemia (FA) is a rare inherited disorder classically defined by defective DNA interstrand crosslink repair, leading to bone marrow failure and cancer predisposition. Increasing evidence indicates that FA pathophysiology extends beyond genomic instability to include mitochondrial dysfunction, oxidative stress, and impaired antioxidant responses. Across multiple cellular models and patient-derived samples, FA cells display altered mitochondrial bioenergetics, increased reactive oxygen species (ROS) production, and defective activation of redox-adaptive pathways, contributing to cumulative damage to DNA, lipids, and proteins. These alterations are particularly relevant in hematopoietic stem and progenitor cells, where metabolic stress and redox imbalance amplify stem cell exhaustion. Current data support a bidirectional interplay in which mitochondrial dysfunction and oxidative stress act mainly as secondary but amplifying factors of the primary DNA repair defect, establishing pathogenic feedback loops. Preclinical studies suggest that modulation of redox balance and mitochondrial function may improve cellular homeostasis, and early clinical investigations of antioxidant strategies indicate acceptable safety and measurable effects on oxidative biomarkers. However, clinical evidence remains limited and heterogeneous, with uncertain impact on long-term disease progression. Moreover, most mechanistic insights derive from in vitro or patient-derived models, while animal models and longitudinal clinical studies remain insufficient. Overall, a more integrated and translational framework is needed to clarify causality, validate biomarkers, and define the therapeutic potential of targeting metabolic and redox pathways in FA. Full article

Background: Pangolins are critically endangered mammals, and a comprehensive understanding of their genetic diversity is crucial for effective conservation. The mitochondrial genome serves as a vital molecular marker for phylogenetic and population genetic studies. Obtaining genetic material from these elusive animals non-invasively remains a challenge. This study aimed to sequence and characterize the complete mitochondrial genome of Manis javanica and explore the phylogenetic relationships among pangolin species. Methods: The complete mitochondrial genome was sequenced from a saliva-derived sample. Standard procedures for DNA extraction, amplification, and sequencing were employed. The genome was assembled and annotated using bioinformatic tools. Phylogenetic analysis was conducted based on the cytochrome c oxidase subunit I (COXI) gene sequences from nine pangolin species, with the resulting tree constructed using the maximum-likelihood method. Results: The complete mitochondrial genome of M. javanica (GenBank accession: PP110760) is a circular molecule of 16,573 bp, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region. The overall base composition showed a lower GC content (43.83%) than AT content (56.17%). Phylogenetic analysis based on COXI sequences delineated the nine species into three distinct genera: Manis, Phataginus, and Smutsia. Within the genus Manis, Manis pentadactyla was identified as the closest relative to M. javanica. The newly described species Manis mysteria was found to be closer to Manis culionensis and Manis crassicaudata than to other congeners. Furthermore, the analysis indicated that African pangolins diverged earlier than Asian pangolins. Conclusions: This study successfully demonstrates the feasibility of extracting and sequencing the complete mitochondrial genome from saliva samples, providing a valuable non-invasive method for future genetic studies on pangolins. The genomic data and phylogenetic results offer significant molecular insights that will benefit the genetic management and conservation of critically endangered pangolin resources. Full article

Positive mental health (PMH) has recently become a key topic in biomedical research. Previous studies have explored the correlation between biological and psychological measures, but only a few have focused on the relationship between PMH and aging. This study aimed: (i) to explore the association between PMH and biological aging; (ii) to determine if and to what extent the observed association could be explained by shared genetic and environmental effects. A total of 401 twins (age 19–81 years, 32% male) from the Italian Twin Registry were recruited, and the twin study design was applied. A self-report psychological test battery was used to evaluate several PMH components. Blood samples were collected from participants to determine telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). TL was negatively associated with attachment anxiety (r = −0.11, p = 0.037). A bivariate twin model provided heritability estimates of 0.14 (95% CI 0.001–0.43) for TL and 0.32 (0.16–0.45) for attachment anxiety, and a substantial negative genetic correlation [r_g = −0.55 (−1.00–0.00)] between them. Under the limitations of a cross-sectional study with a self-report wellbeing assessment, these results suggest that anxiety in a relationship with a partner may contribute to accelerated TL shortening, and shared genetic factors may underlie this link. Full article

Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained lifestyle-related overload. Repeated exposure to psychological stress, sleep disruption, hypercaloric intake, and physical inactivity shifts adaptive signaling toward maladaptation, promoting oxidative damage, protein misfolding, mitochondrial dysfunction, low-grade inflammation, and genomic instability. These interconnected processes contribute to the development and progression of major chronic non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and cancer. Particular emphasis is placed on circadian and neuroendocrine regulation, especially overactivation of the hypothalamic–pituitary–adrenal axis and impaired nocturnal regenerative pathways such as glymphatic clearance and DNA repair. Together, the evidence supports a unifying model in which chronic pathology emerges from cumulative failure of cellular resilience systems rather than isolated organ-specific defects. This perspective highlights sleep optimization, stress reduction, and metabolic regulation as mechanistically grounded strategies for prevention and supportive interventions for chronic disease. Full article

Background: Translocation morphology renal cell carcinoma (tRCC) accounts for nearly half of all pediatric RCC cases. Biological study AREN14B4-Q aimed to characterize the molecular landscape of tRCC using samples acquired from patients enrolled in the Children’s Oncology Group Risk Classification and Biobanking study AREN03B2. Methods: From 2006 to 2014, patients <30 yr old with renal tumors were prospectively enrolled in AREN03B2, a Central IRB-approved biobanking study. All pediatric RCC cases underwent a detailed central pathology review and molecular diagnostics to accurately classify RCC subtypes. Samples with confirmed tRCC and appropriate informed consent were identified with adequate tissue for RNA and DNA extraction, along with germline DNA, for whole-genome sequencing (WGS), RNA sequencing, and DNA methylation analyses. Results: From 41 patients, high-quality samples allowed for 18 tumors and non-tumor DNA to be analyzed via WGS, 19 via DNA methylation, and 36 RNA samples via transcriptome sequencing. Consistent with and extending clinical cytogenetic findings, WGS and fusion transcript analyses confirmed very few additional mutations beyond the tRCC translocation. No recurrent genomic copy number gains/losses were found. RNA and WGS analyses enabled sub-classification of tRCC, closely aligning with the different TFE3 fusion partners. DNA methylation analyses demonstrated less tRCC sub-stratification compared with RNA analyses. Pathways activated in tRCC were involved in epithelial differentiation, extracellular matrix organization, apoptosis, immune regulation, signal transduction, and angiogenesis. Conclusions: Arrested epithelial differentiation is the overarching driver in tRCC and is strongly correlated with the specific subclasses of fusion transcript generated by the genetic translocation TFE fusion partner. Negative regulation of apoptosis, increased M2 macrophage expression, and enhanced angiogenesis also appear to be functional features of tRCCs, as are increased expression of matrix metalloproteinases, PI3K-AKT/mTOR/MAPK signaling, and mitochondrial metabolism, highlighting potential therapeutic options beyond direct targeting of the oncogenic driver fusions. Full article

Populations of several billfish species are declining due to overfishing and bycatch, and fundamental aspects of their biology and population dynamics remain poorly understood. We provide the first assessment of the population genetic structure of longbill spearfish (Tetrapturus pfluegeri) in the western Atlantic Ocean. We screened variation at 12 nuclear microsatellite loci (n = 144) and mitochondrial DNA control region sequences (mtCR, n = 177). Both marker types revealed three genetically differentiated clusters, with mean values for microsatellites showing differentiation of F_ST = 0.136 and D_EST = 0.201, and for mtCR F_ST = 0.645. Microsatellite markers demonstrated moderate-to-high genetic diversity, with a mean allelic richness of 6.73 alleles per locus, moderate heterozygosities (Ho = 0.446, He = 0.604), and a positive inbreeding coefficient (F_IS = 0.22) across the three sample collection sites. The overall estimated effective population size was 789.2 (95% CI: 246.7–∞). The mtCR exhibited 96 haplotypes, with high haplotype (0.989 ± 0.003) and nucleotide (0.025 ± 1.3%) diversities. We found higher mean relatedness within clusters than among them, supporting the interpretation of population subdivision and the Wahlund effect. Tajima’s D and Fu’s Fs were negative across all localities, with significant values observed along the Brazilian coast but not in the Caribbean Sea. These neutrality test results, together with low Harpending’s raggedness indices from DNA sequence mismatch distributions, are consistent with historical demographic expansion. Our findings establish a genetic baseline for fishery monitoring and management, contributing to the conservation of T. pfluegeri populations in the western Atlantic Ocean. Full article

Background/Objectives: Genetic identification of human skeletal remains plays a pivotal role in forensic investigations when other traditional or primary methods are not appropriate. Decomposition, storage and environmental conditions often leave the skeletal structure as the only basis for identification. This review synthesizes current methodologies and technological advances in damaged DNA extraction and analysis, emphasizing the forensic relevance of skeletal remains for genetic identification. Methods: A comprehensive literature analysis highlights the basis of genetic identification; sampling that considers intrinsic and extrinsic factors influencing the DNA yield and its quality; pre-treatment methods; extraction protocols that are suitable for its sensitivity; genetic marker panels that allow for human identification; and statistical evaluation and analysis of the results. The last chapter demonstrates the real-world impact of genetic identification on historical cases, underscoring its broader significance in legal, humanitarian, and socio-historical contexts, supporting a critical evaluation of best practices, methodological robustness, and ethical considerations within the field. Results: Teeth, femur and the petrous portion of temporal bone are the main samples used for genetic analysis. STR profiling and mitochondrial DNA are the gold standard markers for skeletal human identification. Minimally destructive protocols that enhance a high DNA yield are chosen, with silica-based methods being highlighted in the extraction protocols. Next-Generation Sequencing techniques have also improved analytical outcomes, by enabling high-throughput data generation, increased coverage depth, nucleotide-level sequence data, and high-level multiplexing of genetic targets. Conclusions: This review provides a comprehensive framework for researchers and practitioners seeking to optimize genetic identification workflows in forensic sciences and bioarcheology. These methodological advances have significantly increased identification success rates, especially in cases involving degraded or limited skeletal remains. Reviews such as this one help us to identify methodological gaps, ethical concerns, and future research directions, thereby establishing best practices when working with highly degraded skeletal material, supporting more reliable, standardized, and legally defensible applications of genetic identification in forensic, archeological, and humanitarian contexts. Full article

A hybridization assay based on the microfluidic biochip was developed to identify the origin of the Atlantic salmon species. Among the 215 single nucleotide polymorphic (SNP) sites found in the mtDNA of Salmo salar, we located five sites in devising our assay method. We found two sites that worked, while the others generated either insufficient signals or specificity. We have successfully identified the North American origin of the three samples, as confirmed by Sanger sequencing. Full article

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoi-somerase 1 (TOP1)-DNA complexes. We have previously developed a TDP1 inhibitor, compound OL9-116, which is capable of enhancing the action of the anticancer drug topotecan (TPC), a TOP1 poison, in vitro and in vivo. In this study, the inhibition mode of OL9-116 (uncompetitive) was investigated. We have shown that N-terminal domain of TDP1, which is important for the cell function of TDP1 but is not involved in catalysis directly, reduced the inhibitory potency of OL9-116 probably by influencing the conformation of the enzyme. OL9-116 did not reduce cell viability and did not affect mitochondrial membrane potential. OL9-116 enhanced the cytotoxic/antiproliferative effect of TPC on the panel of tumor cells. This effect was not observed on nontumor cells or TDP1-deficient cells. OL9-116 and TPC had different effects on TDP1 and TOP1 gene expression detected by PCR depending on the cell type and the presence of functional TDP1. The direct relation between the effects of the compounds on the gene expression and cell survival was not found. The obtained data indicated a synergistic effect of OL9-116 and TPC, which appeared to be mediated by TDP1 inhibition rather than by an effect on TDP1 gene expression. Full article

Mitochondria are essential organelles that perform irreplaceable functions in neurons. The degeneration of neurons in Alzheimer’s disease (AD) is associated with mitochondrial damage, and Tau pathology represents a significant pathogenic factor in AD. However, the relationship between Tau and mitochondrial dysfunction during neuronal degeneration remains unclear. In this study, we investigated the effects and mechanisms by which extracellular Tau aggregates induce neuronal mitochondrial damage and dysfunction. The results showed that extracellular Tau aggregates lead to structural damage of mitochondria in SH-SY5Y cells and disrupt mitochondrial homeostasis. Extracellular Tau aggregates can also cause mitochondrial oxidative stress and inhibit oxidative phosphorylation in SH-SY5Y cells. Concurrently, extracellular Tau aggregates promote neuronal death through an increase in cytochrome C, mtDNA leakage and activation of the cGAS/STING pathway. We also explored the effects of a single-chain variable fragment antibody (scFv T1) and found that scFv T1 alleviated mitochondrial damage and dysfunction by inhibiting the formation of Tau aggregates. These findings suggest that targeting Tau pathology may be crucial to address neuronal mitochondrial impairment and that reduction of the toxicity associated with extracellular Tau aggregates could help slow Tau pathology progression. Full article

Background: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mellitus, subsequent symptoms are associated with optic nerve atrophy, followed by central nervous system atrophy. Methods: The aim of the study was to analyse magnetic resonance images (MRI) of the brain in combination with single-voxel magnetic resonance spectroscopy (MRS) and to assess the copy number of mitochondrial DNA (mtDNA-CN) in 10 patients with WFS compared with a control group of 17 healthy individuals. Results: A significant decrease in the amount of selected metabolites was observed in WFS patients compared to controls in all assessed brain regions (pons, cerebellum, white matter, thalamus, and hippocampus). For three metabolites, Glutamate (Glu), Glutamate + Glutamine (Glx) and total N-acetylaspartate (TNAA), significant differences in concentrations were found between the study groups in almost all matrices evaluating specific areas of the brain (p < 0.011), with the exception of a trend toward reduced TNAA in the hippocampus (p = 0.065). In addition, patients with WFS had a significant decrease in the mitochondrial-to-nuclear DNA ratio compared to controls (p < 0.0003). Some metabolites, such as N-acetylaspartate and total N-acetylaspartate, showed strong correlations with specific regions of the visual pathway on MRI scans in patients with WFS. Conclusions: Selected brain metabolites and mtDNA-CN may become potential markers of WFS, and the results of this study may be used to define indicators for future therapeutic strategies. Full article