Search Results (47,820)

Aeromonas hydrophila is a major seafood-borne pathogen capable of persisting under preservative-associated stress by entering a viable but non-culturable (VBNC) state, thereby evading culture-based detection. Here, untargeted metabolomics was applied as the primary analytical approach to elucidate metabolic reprogramming during VBNC formation under seafood-relevant preservation conditions. Cells were incubated at 4 °C for 30 days in sodium benzoate-supplemented saline, comparing 0.85% NaCl (culturable condition) and 4% NaCl (VBNC-inducing condition), with sampling every 6 days. Under 4% NaCl with sodium benzoate, culturability declined from 6.18 log CFU/mL at day 0 to undetectable levels by day 30, while cell viability was retained, confirming VBNC induction. UHPLC–ESI–QTOF–MS profiling detected over 893 intracellular metabolic features, of which 518 metabolites were significantly altered between VBNC and culturable states at day 30. Principal component analysis revealed clear, time-dependent metabolic divergence, with the VBNC trajectory explaining 34.4% (PC1) and 11.5% (PC2) of total variance. Pathway enrichment analysis demonstrated significant remodeling of alanine, aspartate and glutamate metabolism (8/28 hits, FDR = 5.7 × 10⁻⁴); arginine biosynthesis (5/14 hits, FDR = 5.44 × 10⁻³); purine metabolism (10/70 hits, FDR = 8.34 × 10⁻³); and pyrimidine metabolism (7/39 hits, FDR = 1.35 × 10⁻²), indicating nitrogen conservation and metabolic downshifting. A robust biomarker panel, including depleted cyclic AMP, aminoadipic acid, hypotaurine, O6-CM-dG, and betaine, and enriched urocanic acid, pipecolic acid, proline, azelaic acid, and orcinol perfectly discriminated VBNC from culturable cells. These findings demonstrate that sodium benzoate-based preservation can induce a metabolically reprogrammed VBNC state in A. hydrophila, highlighting a hidden food safety risk beyond culture-based assessment. Full article

Telerehabilitation—the remote delivery of rehabilitation services—is undergoing a paradigm shift with the convergence of immersive virtual reality (VR) and wearable biosensor technologies. This perspective article outlines a vision for home-based motor and cognitive rehabilitation that is engaging, personalized, and data-driven. We describe how immersive VR environments (for example, simulations of home settings or supermarkets) coupled with wearable sensors can address current challenges in rehabilitation by increasing patient motivation, enabling real-time biofeedback, and supporting remote clinician supervision. Gamification mechanisms and rich sensory feedback in VR are highlighted as key strategies to enhance user engagement and adherence to therapy. We discuss conceptual innovations such as multi-sensor data integration, dynamic difficulty adaptation, and AI-driven personalization of exercises, derived from recent research and our development experience, and consider their potential benefits for patients with neuro-cognitive-motor impairments (e.g., stroke, Parkinson’s disease, and multiple sclerosis). Implementation scenarios for home-based therapy are presented, emphasizing scalability, standardized digital metrics for monitoring progress, and seamless involvement of clinicians via telehealth platforms. We also critically examine the current limitations of VR and telehealth rehabilitation and how an integrative model could overcome these barriers. More specifically, this perspective defines the engineering requirements of a closed-loop VR-based telerehabilitation framework, including multimodal data synchronization, calibration, signal-quality management, interpretable adaptive control, digital biomarker validation, and practical strategies to improve accessibility, privacy, and scalability in home-based neurological rehabilitation. Full article

Background: Post-stroke dysphagia is a frequent complication associated with aspiration, malnutrition, and prolonged dependence on enteral feeding. Systemic inflammation and impaired nutritional status may adversely affect neuromuscular recovery; however, their relative and combined associations with swallowing recovery and transition from enteral to oral feeding remain insufficiently characterized. Objective: This study aimed to examine the independent associations of inflammatory and nutritional indices with swallowing function recovery and to evaluate their relationship with enteral-to-oral feeding transition in patients with post-stroke dysphagia. Methods: In this retrospective observational study, patients with dysphagia following ischemic stroke were evaluated before (T0) and after (T1) routine dysphagia rehabilitation. Inflammatory indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune–inflammation value (PIV), as well as the prognostic nutritional index (PNI), were calculated at both time points. Changes in indices (Δ = T1 − T0) were analyzed in relation to changes in swallowing function assessed by the Functional Oral Intake Scale (FOIS) and the Penetration–Aspiration Scale (PAS). Results: Changes in PNI were independently associated with greater improvement in functional oral intake (ΔFOIS) and reductions in aspiration severity for both liquid and soft consistencies (ΔPAS; all p < 0.01). In contrast, changes in inflammatory indices (ΔSIRI, ΔSII, ΔPLR, and ΔPIV) were consistently associated with less favorable swallowing outcomes. In multivariable logistic regression analysis, baseline stroke severity (NIHSS) was the only independent determinant of transition from enteral to oral feeding (OR = 0.72, p = 0.002). The model demonstrated good discrimination (AUC = 0.81). Conclusions: Changes in nutritional status, as reflected by ΔPNI over time, were the biomarker most consistently associated with functional swallowing recovery and reduced aspiration severity in patients with post-stroke dysphagia. While inflammatory burden was associated with less favorable swallowing physiology, transition from enteral to oral feeding appeared to be primarily driven by neurological severity rather than inflammatory or nutritional indices alone. These findings may support the clinical value of monitoring nutritional reserve alongside inflammatory burden during dysphagia rehabilitation. Full article

Background: Prognostic markers reflecting nutritional vulnerability in idiopathic pulmonary fibrosis (IPF) remain poorly defined. Methods: In this prospective cohort study, 63 stable outpatients with IPF were followed for 3 years. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia criteria. Serum transthyretin levels were measured concurrently. Cox proportional hazards regression, binary logistic regression, and Kaplan–Meier survival analyses were performed. Results: During follow-up, 18 patients (29%) died and 21 (33%) experienced respiratory-related hospitalization. Serum transthyretin was an independent predictor of both 3-year mortality and respiratory-related hospitalization, even after adjusting for the Gender–Age–Physiology index. Conversely, sarcopenia and low appendicular skeletal muscle mass index (ASMI) were not independently associated with either outcome. Kaplan–Meier analysis demonstrated significant differences in both mortality and hospitalization according to serum transthyretin levels. Low ASMI evaluated using sex-specific cutoffs was associated with higher mortality in the unadjusted analysis, but not with hospitalization; sarcopenia was not significantly associated with either endpoint. Conclusions: Serum transthyretin may serve as a practical biomarker of nutritional vulnerability, providing complementary prognostic information beyond muscle mass-based assessment in IPF. Full article

Ferroptosis is an iron-dependent cell death driven by lipid peroxidation and failure of cellular antioxidant defenses. It is triggered by oxidative stress and can be aggravated by aging, inflammation, and dysregulation of iron homeostasis. In the central nervous system, iron dyshomeostasis, mitochondrial dysfunction, and membrane lipid remodeling can amplify oxidative injury and increase susceptibility to ferroptotic damage, particularly in vulnerable neurons. There is growing evidence that ferroptosis-related processes are linked to Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis. This review addresses novel approaches to track ferroptosis in vivo, such as imaging and biomarker techniques, and important molecular mechanisms linking iron metabolism, reactive oxygen species, and PUFA-driven lipid peroxidation to neuronal damage. We also explore upstream transcriptional control via NRF2, iron chelation and iron-handling modulation, inhibition of lipid peroxidation, and reinforcement of the System Xc-GSH-GPX4 and CoQ10-linked defense pathways. Subsequently, we highlight translational issues that need attention to further progress ferroptosis-targeted therapies for neurodegenerative disease. Full article

Background: Human physiology-based biomarkers, such as transcortical long-latency reflexes (LLRs) and movement control performance, are measurements used to evaluate human performance. We developed a method to assess human performance variables using a custom-designed visuomotor control device with the capability to examine performance accuracy and neurophysiological responses to unexpected perturbations. We assessed the internal consistency and reproducibility of this device during a shoulder tracking task including the performance accuracy and the transcortical long-latency reflexes during unexpected perturbations. Methods: 86 healthy young adults (49 females, right-handed, mean age 25.8 ± 9.5 years) were assessed for internal consistency across varying resistance and velocity conditions. We next determined test–retest reliability among 31 participants (17 females, right-handed, mean age 24.13 ± 3.8 years). We then determined the predictability of the LLRs and performance error during perturbations using the receiver operating characteristic analysis (ROC). Results: Our results supported excellent internal consistency, fair-to-good test–retest reliability for task performance accuracy, and fair-to-good transcortical LLR responses to perturbations (McDonald’s omega > 0.9; intraclass correlation coefficients (ICCs, 0.63–0.82)). Tracking accuracy, changes in movement velocity, and infraspinatus LLRs were effective predictors of perturbation conditions (receiver operating characteristics: AUC 0.72–0.90). Conclusions: These findings support that performance-based biomarkers have moderate-to-good reliability and neurophysiology-based biomarkers have fair-to-good reliability when assessing human shoulder performance among healthy adults. Studies are currently underway to determine if these measures are reproducible across other joint movements and among people with musculoskeletal and central nervous system injury. Full article

Fibromyalgia (FM) is a complex chronic syndrome marked by widespread musculoskeletal pain, neurocognitive dysfunction (“fibro-fog”), and autonomic disturbances. Clinical management remains challenging due to subjective symptom reporting and the lack of definitive diagnostics. Emerging evidence points to a multifactorial origin involving central sensitization, neuroendocrine imbalance, and systemic immune-inflammatory alterations. A wide array of candidate biomarkers has been reported in FM, encompassing neurotransmitters (serotonin, norepinephrine), excitatory and inhibitory amino acids, metabolic and glycolytic enzymes, stress-related proteins, autoantibodies, oxidative stress markers and pro-inflammatory cytokines. This molecular heterogeneity reflects the systemic and multidimensional nature of FM. However, most of these biomarkers have been primarily investigated in serum or plasma, where analytical validation and reference ranges are more established. In contrast, the exploration of salivary biomarkers—although highly attractive due to its non-invasive, stress-free, and repeatable collection—remains comparatively limited. Saliva contains a reduced concentration range of many systemic markers and is strongly influenced by circadian rhythms, stress, flow rate, and oral health conditions. While promising candidates such as α-amylase, cortisol, calgranulins, and selected metabolic enzymes have shown potential in saliva, many proposed FM-related biomarkers lack full analytical validation, standardized protocols, and clinically defined reference intervals in this matrix. In this context, non-invasive electrochemical biosensors represent a transformative technological approach. Advanced electrode architectures incorporating nucleic acid probes, redox reporters, and nanostructured materials offer high sensitivity in low-volume and low-concentration biofluids such as saliva. The integration of multiplexed biomarker panels into portable platforms could enable real-time, longitudinal monitoring of FM pathophysiology, supporting phenotype stratification, personalized therapeutic adjustment, and objective disease activity tracking. Full article

Preeclampsia (PE), pregnancy-associated high blood pressure linked to organ damage, affects 3–8% of all pregnancies and results worldwide in 70,000 maternal and 500,000 perinatal deaths each year. Untreated PE may progress to eclampsia with long-term health implications for both mother and child. Non-invasive prenatal diagnosis or screening applies cell-free DNA approaches and offers a less invasive and more economical method for early diagnosis and prediction of various pregnancy complications. Recently, cell-free assays, particularly blood-based cell-free DNA and RNA analysis, have shown great potential in early PE prediction and diagnosis. Here, we provide an updated review of the current understanding and discoveries of PE, focusing on recent publications (1 January 2019–30 December 2025) of liquid biopsy-derived circulating fetal cells (circulating trophoblasts and fetal nucleated red blood cells), cell-free DNA, cell-free RNA and small extracellular vesicles (i.e., exosomes). We aim to discuss the conceptual framework and technical evolution of liquid biopsy applications in preeclampsia pathogenesis, prediction and diagnosis. Progressing novel screening and diagnostic molecular biomarkers have high potential to facilitate early detection for patients at risk of PE. Liquid biopsy-based screening strategies may aid in providing timely intervention and treatment. Full article

Despite substantial advances in our understanding of cancer metastasis, it remains the leading cause of mortality among cancer patients. Elucidating the molecular mechanisms that drive metastatic progression is expected to facilitate the development of more effective therapeutic strategies. Among the numerous candidates, the long non-coding RNA H19 and its derivative miR-675 have been increasingly recognized as key regulators of metastatic dissemination in cancers of diverse tissue origins. In this review, we provide an up-to-date overview of the H19/miR-675 axis in metastatic progression, with particular emphasis on its involvement in the dynamic and complementary processes of epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET). We also highlight the opportunity to consider the H19/miR-675 axis as promising biomarkers and potential therapeutic targets. Full article

Background/Objectives: Objective, non-invasive biomarkers are needed to track anterior cruciate ligament (ACL) graft maturation and support individualized return-to-sport decisions. This study evaluated a single-session multiparametric quantitative MRI (qMRI) protocol for longitudinal assessment of ACL graft microstructural evolution and its association with patient-reported outcomes. Methods: Twenty-eight patients undergoing primary ACL reconstruction with hamstring autografts underwent multiparametric qMRI (T1, T2*, R2*, and PD mapping) at 1, 3, 6, and 12 months. The contralateral native ACL served as a within-subject control. IKDC, Lysholm, and VAS scores were recorded at each visit. Linear mixed-effects models were used to test longitudinal changes. Correlations of baseline-normalized changes between adjacent visits were used to evaluate imaging–clinical associations. Results: All qMRI parameters changed significantly over time (all p < 0.001). At 1 month, T1, PD, and T2* were lower and R2* higher than the contralateral native ACL (all p < 0.001). Thereafter, T1, PD, and T2* increased and R2* decreased, with most metrics approaching contralateral values by 3–6 months (all p < 0.05), and changes entered a plateau after 6 months (all p > 0.05). IKDC, Lysholm, and VAS improved over time (all p < 0.001), mainly before 6 months. Greater early T2* increases and R2* decreases (1–3 months) were associated with less pain relief and smaller Lysholm improvement (p < 0.05); no significant associations were observed from 6–12 months. Conclusions: Single-session multiparametric qMRI sensitively captures ACL graft maturation and highlights 3–6 months as a critical remodeling window, providing objective biomarkers to complement clinical assessment for individualized rehabilitation monitoring and return-to-sport timing. Full article

The development of reliable electrochemical interfaces for biosensor applications requires materials that combine high conductivity, large effective surface area, and suitable platforms for biomolecule immobilization. In this work, a hybrid electrochemical platform based on screen-printed carbon electrodes (SPCEs) modified with electropolymerized polypyrrole (PPy) and electrodeposited silver particles (AgPs) is presented for the subsequent immobilization of Ki-67 antibodies. PPy films were synthesized under optimized electrochemical conditions, producing homogeneous, porous, and electrochemically stable coatings that significantly enhanced the doping/undoping processes from 0.3280 C/0.3284 C to 0.3281 C/0.3284 C for SPCE and SPCE-PPy, respectively. Subsequently, silver particles were deposited onto the PPy matrix, resulting in a well-dispersed and uniform distribution of AgPs, promoted by the interaction between Ag⁰ and the nitrogen groups in the polymer backbone. The synergistic combination of PPy and AgPs resulted in improved charge-transfer properties and enhanced electrochemical reversibility, thereby decreasing the peak-to-peak separation of the ferricyanide/ferrocyanide redox couple used as a probe by 40%. Immobilization of Ki-67 antibodies was achieved via direct interaction with AgPs, resulting in a marked passivation effect, as evidenced by the suppression of redox probe signals, confirming successful biofunctionalization. The proposed SPCE-PPy-AgP architecture provides a robust, reproducible, and versatile platform for antibody immobilization, as demonstrated by oxidation and reduction peaks with relative standard deviations (RSDs) of 3.18% and 4.43%, respectively, highlighting its potential for developing label-free electrochemical immunosensors for clinically relevant proliferation biomarkers. Full article

Chronic kidney disease (CKD) is a progressive condition associated with metabolic disturbances, systemic inflammation, and the accumulation of gut-derived uremic toxins. Increasing evidence highlights the role of gut microbiota dysbiosis in the progression of CKD through the gut–kidney axis. Consequently, microbiome-targeted nutritional strategies, including probiotics, prebiotics, and synbiotics, have emerged as promising complementary approaches to modulate intestinal microbial composition and metabolic functions. This review summarizes and critically evaluates the current clinical evidence regarding the use of these interventions in CKD patients. Clinical studies indicate that supplementation with probiotics, prebiotics, and synbiotic formulations may promote beneficial shifts in the composition of the gut microbiota, enhance saccharolytic fermentation, and increase the production of short-chain fatty acids (SCFAs). These changes have been associated with reduced circulating levels of gut-derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate, as well as with the attenuation of systemic inflammation and oxidative stress. However, available trials remain heterogeneous in terms of study design, probiotic strains, prebiotic substrates, dosing regimens, and patient populations, and are frequently limited by small sample sizes and short intervention durations. As a result, evidence for improvements in renal function and long-term clinical outcomes remains inconclusive. While synbiotics may offer theoretical advantages by combining microbial supplementation with targeted substrates that support microbial growth and metabolic activity, current evidence does not consistently demonstrate superior clinical efficacy. Overall, these interventions often improve surrogate biomarkers, but their effects on renal function and hard clinical outcomes remain uncertain. Larger, longer-duration multicenter randomized controlled trials with standardized formulations are needed to establish their clinical utility and to better elucidate microbiota–host interactions in CKD. Advancing this field may support the development of personalized microbiome-based therapeutic strategies aimed at modulating the gut–kidney axis and ultimately improving clinical outcomes in CKD patients. Full article

The effects of chronic intermittent hypoxia associated with obstructive sleep apnea (OSA) on iron metabolism remain incompletely understood. This study aimed to evaluate whether serum hepcidin levels are associated with OSA severity independently of obesity and systemic inflammation. A total of 136 patients who underwent polysomnography for suspected OSA between April and December 2025 were included in the study. Participants were classified into control and OSA groups according to the Apnea–Hypopnea Index (AHI), and the OSA group was further categorized as mild, moderate, or severe. Demographic and anthropometric characteristics and Epworth Sleepiness Scale scores were recorded. Serum hepcidin levels were measured using an ELISA method and compared between groups, and their associations with clinical and polysomnographic parameters were analyzed. Serum hepcidin levels were significantly higher in patients with OSA than in the control group (48.83 ± 11.92 vs. 41.53 ± 12.43 ng/mL; p < 0.001) and increased progressively with disease severity. Hepcidin levels were not significantly correlated with conventional iron parameters but showed a strong positive association with the Oxygen Desaturation Index (ODI). In multivariable regression analysis, the positive relationship between AHI and serum hepcidin levels remained significant after adjustment for body mass index and C-reactive protein levels (p < 0.001). These findings suggest that elevated serum hepcidin levels in OSA are linked to hypoxic stress independently of obesity and systemic inflammation, indicating that hepcidin may represent a potential biomarker reflecting disease severity in OSA. Full article

Psychological stress is a major public health problem associated with adverse outcomes in physical and mental health. This study proposes an approach to predicting clinical stress levels using metabolic and endocrine biomarkers combined with machine learning models based on genetic algorithms. Data were obtained from 87 university students, including measurements of glucose, insulin, and cortisol, as well as perceived stress scores assessed using the Perceived Stress Scale (PSS). Stress levels were categorized into low ($n=5$), moderate ($n=22$), and high ($n=60$) classes, reflecting an imbalanced dataset. Feature engineering and genetic algorithm–based selection identified glucose concentration, the insulin–glucose ratio, and the insulin–cortisol ratio as the most relevant features. These were used to train XGBoost and Elastic Net models, which were evaluated using leave-one-out cross-validation. The XGBoost model achieved the best performance, with an accuracy of 0.77 and strong predictive capability for high stress levels. The results demonstrate the usefulness of machine learning based on metabolic biomarkers as an objective tool for stress assessment in psychological and clinical research. Full article