Life-Basel最新文献

Continuous exposure to stress contributes to species diversity and drives microevolutionary processes. It is still unclear, however, whether epigenetic changes, in the form of epimutations such as, for example, differential DNA methylation, are the pre-requisite to speciation events. We hypothesized that continuous stress exposure would increase epigenetic diversity to a higher extent than genetic diversity. In this work, we have analyzed the effect of 25 consecutive generations of UV-C-stress exposure on the Arabidopsis thaliana genome and epigenome. We found no evidence of increased tolerance to UV-C in the progeny of UV-C-stressed plants (F25UV) as compared to the progeny of control plants (F25C). Genetic analysis showed an increased number of single nucleotide polymorphisms (SNPs) and deletions in F25UV plants. Most common SNPs were mutations in cytosines, C to T, C to A, and C to G. Analysis of cytosine methylation showed a significant increase in the percentage of methylated cytosines at CG context in F25UV as compared to F25C or F2C (parental control). The most significant differences between F25UV and either control group were observed in CHG and CHH contexts; the number of hypomethylated cytosines at CHH contexts was over 10 times higher in the F25UC group. F25UV plants clustered separately from other groups in both genomic and epigenomic analyses. GO term analysis of differentially methylated genes revealed enrichments in "DNA or RNA metabolism", "response to stress", "response to biotic and abiotic stimulus", and "signal transduction". Our work thus demonstrates that continuous exposure to UV-C increases genomic and epigenomic diversity in the progeny, with epigenetic changes occurring in many stress-responsive pathways.

Background/objectives: Vestibulo-ocular reflex (VOR) function, measured by the video head impulse test (vHIT) gains, plays a crucial role in postural stability and quality of life. Cochlear implant recipients often experience vestibular dysfunction, but its relationship with balance and patient-reported outcomes remains underexplored. This study aimed to (1) evaluate the relationship between vHIT gains and postural stability in cochlear implant recipients; (2) assess the impact of vHIT gains on quality-of-life metrics; and (3) identify key predictors of postural stability, including vHIT gains and demographic/clinical characteristics.

Methods: This cross-sectional study was conducted between August 2023 and February 2024 and included 46 participants that comprised cochlear implant recipients and age-matched normal hearers who underwent the vHIT for lateral, anterior, and posterior semicircular canal function. Postural stability was assessed using dynamic posturography, and quality of life was measured using the Short Form-36 (SF-36). Multiple linear regression and correlation analyses were performed.

Results: The vHIT gains demonstrated significant positive correlations with postural stability, with the lateral canal showing the strongest association (r = 0.742, p = 0.001), followed by the posterior (r = 0.701, p = 0.003) and anterior canals (r = 0.684, p = 0.005). A multiple regression analysis identified the lateral canal as the most significant predictor of postural stability (β = 0.512, p = 0.001, adjusted R² = 0.47). Quality-of-life metrics were inversely correlated with the vHIT gains, particularly in the posterior canal (r = -0.712, p = 0.002), which explained 43-51% of the variance.

Conclusions: This study highlighted the lateral semicircular canal as the primary determinant of postural stability in cochlear implant recipients, underscoring the importance of vestibular assessments in optimizing balance and functional outcomes.

Myeloproliferative neoplasm (MPN) with eosinophilia associated with FIP1L1-PDGFRA is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent FIP1L1-PDGFRA T674I and PTPN11 (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with FIP1L1-PDGFRA T674I-positive eosinophilic disorder, especially when compounded by the PTPN11 mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease.

This study investigates seasonal and gender-related variations in some metal (Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn) accumulation in black scorpionfish (Scorpaena porcus) from Izmir Bay (Aegean Sea, Türkiye) and assesses the associated human health risks. Samples, collected across four seasons from 2023 to 2024, were analyzed for element concentrations using inductively coupled plasma mass spectrometry (ICP-MS). Health risks were calculated using several models, including estimated weekly intake (EWI), target hazard quotient (THQ), total THQ (∑THQ), carcinogenic risk (CR), Se health benefit value (HBVSe), and the Metal Pollution Index (MPI). The results indicate that the consumption of black scorpionfish poses potential health risks, primarily due to the accumulation of manganese (Mn), lead (Pb), and mercury (Hg), which exceeded international permissible legal limits. Gender-based differences were observed, with males showing higher accumulation (p > 0.05); however, these differences were not statistically significant. In contrast, significant sex-based differences were identified specifically for cadmium (Cd), with concentrations exhibiting a statistically meaningful difference (p < 0.05). Seasonal variations were also apparent (p < 0.05). The carcinogenic risk (CR) analyses revealed that chromium (Cr) and nickel (Ni) levels surpassed carcinogenic risk thresholds. Furthermore, the MPI values provided additional insights into the overall metal pollution levels in the fish. These findings underscore the critical importance of monitoring metal pollution, revising fishery management strategies, and managing fish consumption to safeguard public health.

Background/Objectives: Hair loss affects self-esteem, confidence, and psychological well-being. Exosomes, as molecular carriers of growth factors and active compounds, offer a promising treatment. This study evaluates the efficacy of an exosome formulation containing extracts from two known hair-regenerating plants, Ecklonia cava and Thuja orientalis (ECPE), for male pattern alopecia. Methods: A randomized controlled trial included 20 male participants with Norwood grade 2-3 androgenetic alopecia who were randomly assigned into two groups, placebo (0.9% sodium chloride) and ECPE, administered bi-weekly across four sessions. Evaluations included hair density measurements, adverse effect tracking, and self-assessments. Results: Most participants (55%) were aged 18 to 35, with 75% reporting hair loss for over a year and 80% noting scalp thinning. The hair counts showed no significant change in the placebo group from baseline to week 16 (Wilcoxon signed-rank test: V = 13.5, p = 0.163), while a significant increase was observed in the ECPE group (V = 0, p = 0.002). Between-group analysis revealed a significant difference in the hair count changes (Wilcoxon rank-sum test: W = 86.5, p = 0.006) with a large effect size (Cliff's Delta: & = 0.73, 95% CI: 0.41-0.89), with the ECPE group showing higher median hair growth (9.5, IQR = 16.88) compared to the placebo group (1.5, IQR = 3.00). A Bayesian ANCOVA, adjusted for covariates (the father's scalp hair condition, baseline hair count, and Norwood classification), showed no significant effect of these factors on the outcomes. Conclusions: These findings suggest that ECPE significantly improves hair regrowth compared to the placebo, with no notable adverse effects.

Traumatic brain injury (TBI) represents a significant public health issue, causing long-term disabilities and imposing considerable socioeconomic and healthcare challenges. While advancements in acute care have improved survival rates, the demand for effective neurorehabilitation is increasing. This narrative review explores the evidence on neurorehabilitation strategies for TBI, focusing on interventions targeting cognitive, motor, and psychological recovery. A total of 32 studies were included and categorized into six approaches: non-invasive brain stimulation, virtual reality (VR), computer-based training, telerehabilitation, robot-assisted therapy (RAT), and mixed approaches. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), showed variable effectiveness in improving cognitive outcomes. VR-based therapies enhanced attention and executive functions, while RAT, such as Lokomat and exoskeletons, improved gait symmetry and functional mobility. Computer-assisted programs demonstrated benefits in rehabilitating social cognition and executive functions. Telerehabilitation and telephone-based treatments provided short-term gains but lacked sustained effects. Overall, cognitive improvements were better described and represented, while several motor improvements lacked consistency. Despite the promising results, significant gaps remain, including heterogeneity in methodologies, small sample sizes, and limited long-term outcome data.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at a high risk of atherosclerotic cardiovascular disease. The coronary artery calcification (CAC) score by the Ct-scan Agatston calcium score (ACS) > 100 classifies FH at a higher risk. The echocardiographic calcium score (ECS) evaluates aortic valve calcifications and is considered a good predictor of the atherosclerotic burden and cardiovascular outcome.

Objective: To test the ECS as a predictor of ACS > 100 in a HeFH cohort.

Methods: A coronary calcium CT scan with the calculation of ACS and an at rest-transthoracic echocardiogram with ECS evaluation were performed in 81 HeFH patients. Patients were divided into two groups according to the ACS: high-risk ACS patients (High-ACS) with Agatston value > 100 and low risk ACS patients (Low-ACS) with Agatston value ≤ 100. Patients were stratified according to ECS = 0 or ECS > 0.

Results: High-ACS patients were older than Low-ACS patients; BMI, waist circumference, and blood systolic pressure were significantly higher (p < 0.001) in High-ACS patients. The ECS predicted an ACS > 100 with sensitivity = 0.84, specificity = 0.89, accuracy = 0.86, and precision = 0.76.

Conclusions: The ECS could be a good surrogate of a coronary calcium CT scan for ACS evaluation in the specific subset of HeFH patients.

The ubiquitin-proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial for proper immune function. Moreover, the impact of the UPS is considered essential in understanding several diseases, such as neurodegenerative disorders, infections, and vascular diseases. The dysregulation of the UPS may contribute to the pathogenesis of these conditions, highlighting its importance as a potential therapeutic target. Interestingly, the UPS is also related to ocular structures, playing a role in visual perception and ocular homeostasis. This involvement in the regulation of various ocular processes suggests its potential impact on both anterior and posterior eye pathologies. This review aims to discuss the general considerations of the UPS and provide information about its participation in anterior and posterior eye pathologies. By understanding its role in ocular health and disease, researchers and clinicians may explore novel therapeutic strategies targeting the UPS for the treatment of various eye conditions. In conclusion, the UPS is a crucial player in biological processes, with far-reaching implications in health and disease, including the anterior and posterior segments of the eye. Further research in this field may lead to the development of innovative therapies and a better understanding of the complex mechanisms underlying various eye disorders.

Pathogenic variants in the NEXMIF gene are associated with a broad neurodevelopmental phenotype, including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. However, the role of NEXMIF in specific epileptic syndromes remains insufficiently explored. We present the case of an 11.9-year-old Romanian girl diagnosed with ASD, attention-deficit/hyperactivity disorder (ADHD), mild ID, and Jeavons syndrome (generalized epilepsy characterized by eyelid myoclonia, absence seizures, and photosensitivity). Genetic testing identified a pathogenic NEXMIF variant: c.1882C>T (p.Arg628*), a pathogenic variant rarely reported in the literature, with only two documented cases to date. To better understand the genotype-phenotype correlation, we conducted a systematic review of NEXMIF-associated disorders and compared our findings with previously reported cases. Our analysis suggests that NEXMIF variants may contribute to a broader spectrum of epileptic syndromes, including photosensitive epilepsy such as Jeavons syndrome. This highlights the need for a greater awareness of atypical seizure presentations in individuals with NEXMIF-related disorders. This study underscores the importance of genetic testing in individuals with overlapping ASD and epilepsy phenotypes as early diagnosis may facilitate targeted therapeutic interventions and genetic counseling. Further research is needed to clarify the molecular mechanisms linking NEXMIF dysfunction to epileptic syndromes and neurodevelopmental disorders.

Several machine learning classification algorithms were evaluated using a dataset focused on heart failure. Results obtained from logistic regression, random forest, decision tree, K-nearest neighbors, and multilayer perceptron (MLP) were compared to obtain the best model. The random forest method obtained specificity = 0.93, AUC = 0.97, and Matthews correlation coefficient (MCC) = 0.83. The accuracy was high; therefore, it was considered the best model. On the other hand, K-nearest neighbors and MLP (multi-layer perceptron) showed lower accuracy rates. These results confirm the effectiveness of the random forest method in identifying heart failure cases. This study underlines that the number of features, feature selection and quality, model type, and hyperparameter fit are also critical in these studies, as well as the importance of using machine learning techniques.