Search Results (96)

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, in part due to late diagnosis and limited prognostic tools. In recent years, microRNAs, small, non-coding regulators of gene expression, have emerged as key modulators of tumor metabolism, microenvironmental crosstalk, and therapeutic response in HCC. This narrative review synthesizes evidence published from January 2000 through April 2025, focusing on four interrelated themes: (1) miRNA-driven metabolic rewiring; (2) circulating and exosomal miRNAs as diagnostic and (3) predictive biomarkers; (4) miRNA-based therapeutic strategies. We conducted a targeted PubMed search using terms related to HCC, miRNA biology, biomarkers, metabolism, and therapy, supplemented by manual reference mining. Preclinical and clinical studies reveal that loss of tumor-suppressor miRNAs and gain of oncomiRs orchestrate glycolysis, lipid and glutamine metabolism, and stromal-immune remodeling. Circulating miRNA signatures, including single- and multimarker panels, demonstrate diagnostic AUCs up to 0.99 for early-stage HCC and distinguish HCC from cirrhosis more accurately than alpha-fetoprotein. Predictively, miRNAs such as miR-21 and miR-486-3p correlate with sorafenib resistance, while tissue and exosomal miRNAs forecast recurrence and survival after curative therapy. Therapeutic manipulation, restoring tumor-suppressor miRNAs via mimics or AAV vectors and inhibiting oncomiRs with antagomirs or LNA oligonucleotides, yields potent anti-tumor effects in models, affecting cell cycle, apoptosis, angiogenesis, and immune activation. Despite technical and delivery challenges, early-phase trials validate target engagement and inform safety optimization. In this review, we highlight opportunities to integrate miRNA biomarkers into surveillance algorithms and combine miRNA therapeutics with existing modalities, charting a roadmap toward precision-guided management of HCC. Full article

Hair loss (alopecia) is a common disorder caused by an interruption in the body’s cycle of hair production. This pathology negatively affects the psychoemotional state of patients and significantly reduces their quality of life. The currently available medical treatments (including minoxidil therapy) are effective in arresting the progression of the disease; however, they allow only partial regrowth of hair at best. A significant clinical result occurs only with regular drug use. There is still great interest in finding new drugs for the treatment of alopecia. In this study, we aimed to examine the effect of an aqueous dispersion of unmodified fullerene C60 (ADF) on hair growth. ADF, produced by a unique technology, is biocompatible and non-toxic. Nu/nu mice were subcutaneously injected (2 μg/animal) every two days for a period of 11 days with ADF and, for control purposes, with phosphate-buffered saline (PBS). It was shown that ADF stimulated hair growth. Histological analysis of the nu/nu mice skin areas showed that animals treated with ADF had significantly more (about twice as many) hair follicles in the anagen phase compared to mice treated with PBS. The effect on hair growth persisted even after discontinuation of ADF administration. Analysis of gene expression demonstrated that ADF affected the Wnt-signaling pathway, increased the expression of the Wnt10b (wingless-type Mouse Mammary Tumor Virus integration site family, member 10B) factor, angiogenetic factors, and downregulated tumor necrosis factor-alpha levels. We propose that the mechanism of ADF action is likely related to its ability to attract macrophages to the hair follicle microenvironment and promote their polarization to the M2 phenotype. In addition, using molecular modeling, we tried to substantiate our hypothesis about the interaction of ADF with the adenosine A2A receptor, which may cause a decrease in tumor necrosis factor-alpha production. Thus, ADF may become a promising drug for the development of new approaches to the treatment of alopecia associated with immune disorders. Full article

In recent years, scientific interest in functional ingredients capable of replacing the non-therapeutic use of antibiotics in animal feed has intensified, fostering the exploration of novel additives such as Saccharomyces cerevisiae hydrolysate (SCH). This study investigated the effect of dietary SCH supplementation on growth performance, intestinal morphology, local immune response, and cecal microbiota composition in Ross 308 broiler chickens. A total of 300 one-day-old male chicks were randomly assigned to two experimental groups, receiving either a standard diet or a diet supplemented with SCH (500 mg/kg during the starter and grower phases; 250 mg/kg during the finisher phase). SCH supplementation significantly improved growth performance during the finisher phase, with increases in final body weight (p = 0.025), average daily gain (p = 0.049), and average daily feed intake (p = 0.027), without significant changes in feed conversion ratio (p > 0.05). Favourable intestinal morphological modifications were observed, with a significant increase in villus height to crypt depth ratio in both the jejunum and ileum at days 28 (p = 0.035 and 0.002, respectively) and 42 (p < 0.001). The expression of pro-inflammatory cytokine genes was significantly reduced, with lower levels of TNF-α, IL-1β, and IL-6, while tight junction protein genes ZO-1 and Occludin were significantly upregulated (p < 0.05). Microbiota profiling revealed higher alpha diversity and greater abundance of Prevotella. These findings highlight SCH as a promising dietary strategy to improve broiler performance, intestinal function, and sustainability in poultry production systems. Full article

Background/Objectives: Pain assessment scales provide a clear clinical benefit in patients who are unable to self-report. The Nociception Coma Scale-Revised—adapted for Intubated patients (NCS-R-I) was developed to assess pain in patients with acquired brain injury who are unable to self-report. However, this instrument has not yet been translated and validated for use in Spain. The objective was to translate the Nociception Coma Scale-Revised—adapted for Intubated patients (NCS-R-I) into Spanish and to assess the reliability and validity of the Spanish version in patients with brain injury. Methods: This study was carried out in two phases. First, the scale was translated into Spanish. Next, a psychometric analysis was performed to determine the reliability and validity of the Spanish version of the NCS-R-I in 207 critically ill patients with acquired brain injury and disorders of consciousness. Two blinded observers administered the scale at three time points: 5 min before, during, and 15 min after a series of nociceptive and non-nociceptive procedures. Results: The internal consistency of the NCS-R-I was acceptable (ordinal alpha = 0.60–0.90). Interobserver agreement was good (kappa = 0.80; intraclass correlation coefficient = 0.90). In terms of discriminant validity, the AUC was 0.952 (95% CI: 0.931–0.973). NCS-R-I scores increased significantly during performance of nociceptive procedures compared to scores obtained before and after these procedures, confirming the scale’s sensitivity to change. Similarly, during the performance of nociceptive procedures, scores on the NCS-R-I were significantly higher (p < 0.001) than those observed during non-nociceptive procedures. Conclusions: The results of this study demonstrate that the NCS-R-I is a valid, reliable tool for the assessment of pain in patients with acquired brain injury who are unable to self-report. Full article

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Parkinson’s disease (PD) is a progressive neurological disorder with motor and non-motor symptoms that are inadequately addressed by current pharmacological and surgical therapies. Brain–computer interfaces (BCIs), particularly those based on electroencephalography (eBCIs), provide a promising, non-invasive approach to personalized neurorehabilitation. This narrative review explores the clinical potential of BCIs in PD, discussing signal acquisition, processing, and control paradigms. eBCIs are well-suited for PD due to their portability, safety, and real-time feedback capabilities. Emerging neurophysiological biomarkers—such as beta-band synchrony, phase–amplitude coupling, and altered alpha-band activity—may support adaptive therapies, including adaptive deep brain stimulation (aDBS), as well as motor and cognitive interventions. BCIs may also aid in diagnosis and personalized treatment by detecting these cortical and subcortical patterns associated with motor and cognitive dysfunction in PD. A structured search identified 11 studies involving 64 patients with PD who used BCIs for aDBS, neurofeedback, and cognitive rehabilitation, showing improvements in motor function, cognition, and engagement. Clinical translation requires attention to electrode design and user-centered interfaces. Ethical issues, including data privacy and equitable access, remain critical challenges. As wearable technologies and artificial intelligence evolve, BCIs could shift PD care from intermittent interventions to continuous, brain-responsive therapy, potentially improving patients’ quality of life and autonomy. This review highlights BCIs as a transformative tool in PD management, although more robust clinical evidence is needed. Full article

Testicular germ cell tumors (TGCTs) are the most common malignancies affecting young men between the ages of 14 and 44, accounting for about 95% of all testicular cancers. Despite being relatively rare compared to other cancers (~3.0 cases per 100,000 population, with high worldwide variability), TGCTs’ incidence is increasing, particularly in industrialized countries. The initial phase of TGCT diagnosis is performed by detecting in the blood the presence of three proteins, i.e., alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Despite these proteins being defined as markers of TGCTs, they present limitations in specificity. Indeed, AFP is not elevated in pure seminomas; LDH serum levels can be elevated in other conditions, such as liver disease or tissue damage, and hCG can be elevated in both seminomas and non-seminomas, reducing its ability to differentiate between tumor types. However, the existence of hCG variants, characterized by distinct glycosylation profiles that are differentially expressed in TGCT types and subtypes, may increase the diagnostic and prognostic potential of this hormone. Furthermore, emerging molecular biomarkers, including miRNAs and tumor cells-related epigenetic status, may offer new promising alternatives to improve diagnostic accuracy. Nonetheless, standardized diagnostic protocols still need to be implemented. Finally, understanding the biological roles of hCG isoforms and their “canonical” (e.g., LHCGR) and “non-canonical” (e.g., TGF-βR) receptor interactions may help in understanding tumor biology and therapeutic targeting. Full article

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A₂s (PLA₂s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA₂s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA₂) is consistent with the neurotoxic clinical effects of envenomation in humans. Full article

Objectives: The aim of this study was to validate the Polish version of the Somatosensory Amplification Scale (SSAS-PL) and examine its psychometric properties in clinical and non-clinical samples. Methods: The study included 1128 participants (711 healthy adults, 194 cardiac patients, 223 psychiatric patients). The analyses were categorized into exploratory and confirmatory phases. Exploratory analyses were conducted on a randomly selected sample that comprised 60% of the study participants (training sample) to estimate the reliability (Cronbach’s alpha) and factorial validity (EFA with varimax rotation). Confirmatory analyses were performed on an independent (test) sample that represented 40% of the total sample size to facilitate the cross-validation of the factor structure (CFA) and to assess the convergent and discriminant validities (using the HTMT method) in relation to health anxiety (SHAI) and psychopathological symptoms (KOFF-58). Additionally, measurement invariance was examined with respect to gender (female vs. male) and health status (healthy vs. clinical). Results: The SSAS-PL demonstrated good internal consistency (α = 0.75–0.78) after removing item 1. A one-factor structure showed the best fit and theoretical interpretability. The measurement invariance was supported across clinical groups. The SSAS-PL showed convergent validity with the measures of somatic symptoms, anxiety, and health anxiety. It demonstrated discriminant validity from other psychopathology measures. Conclusions: The SSAS-PL was a reliable and valid measure of somatosensory amplification in the Polish population. Its unidimensional structure aligned with most cross-cultural adaptations. The scale may be useful for assessing somatosensory amplification in both research and clinical settings in Poland. Further research on its utility in specific clinical populations is warranted. Full article

The hypertrophic cardiomyopathy (HCM) clinical phenotype includes sarcomeric HCM, which is the most common form of inherited cardiomyopathy with a population prevalence of 1:500, and phenocopies such as cardiac amyloidosis and Anderson–Fabry disease, which are considered rare diseases. Identification of cardiac and non-cardiac red flags in the context of multi-organ syndrome, multimodality imaging, including echocardiography, cardiac magnetic resonance, and genetic testing, has a central role in the diagnostic pathway. Identifying the specific disease underlying the hypertrophic phenotype is very important since many disease-modifying therapies are currently available, and phase 3 trials for new treatments have been completed or are ongoing. In particular, many chemotherapy agents (alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting clonal cells) allowing one to treat AL amyloidosis, transthyretin stabilizers (tafamidis and acoramidis), and gene silencers (patisiran and vutrisiran) are available in transthyretin cardiac amyloidosis, and enzyme replacement therapies (agalsidase-alpha, agalsidase-beta, and pegunigalsidase-alpha) or oral chaperone therapy (migalastat) can be used in Anderson–Fabry disease. In addition, the introduction of cardiac myosin inhibitors (mavacamten and aficamten) has deeply modified the treatment of hypertrophic obstructive cardiomyopathy. The aim of this review is to describe the new disease-modifying treatments available in HCM and phenocopies in light of current scientific evidence. Full article

Background: Target enhancement and non-target suppression are two critical mechanisms underlying representational prioritization in visual working memory (VWM). However, it remains unclear how VWM load modulates these prioritization mechanisms. Methods: Using EEG combined with a retro-cue paradigm, this study investigated how representational prioritization emerges under low (Experiment 1) and high (Experiment 2) memory load conditions. Methods: Behavioral results showed that under low load, both target and non-target items benefited from retro-cue. ERP analyses revealed significantly larger P2 and P3b amplitudes in response to valid compared to neutral retro-cues, whereas no significant contralateral delay activity (CDA) component was observed. Under high load, cueing benefits were restricted to target items, whereas non-target items suffered impaired performance. ERP analyses again showed enhanced P2 and P3b amplitudes for valid compared to neutral retro-cues, but a significant CDA component was also observed. Time–frequency analyses further revealed frontal theta synchronization (ERS) and posterior alpha desynchronization (ERD) under both load conditions. Notably, theta–alpha phase–amplitude coupling (PAC) was significantly stronger for valid than neutral retro-cues under low load, whereas under high load, PAC did not significantly differ between cue conditions. Conclusions: Together, these findings suggest that target enhancement serves as a stable mechanism for representational prioritization, whereas non-target suppression critically depends on resource availability. VWM load systematically shapes representational prioritization through modulation of oscillatory timing characteristics and inter-regional neural coordination. Full article

Background/Objectives: Long COVID is a condition that was initially recognized by social support groups, and later by the scientific and medical communities. It affects COVID-19 survivors at various levels of severity, including young people, children and non-hospitalized people. Although the exact definition is unclear, the most common symptoms are fatigue and shortness of breath, which persist for months. Other symptoms include cognitive impairment, pain, palpitations, and gastrointestinal and heart problems. This study evaluated the reliability and validity of a questionnaire designed to examine the development and effects of long COVID. Methods: A questionnaire, composed of three sections, with a total of 24 items, was administered to subjects who had recovered from the COVID-19 disease in Italy. Data were collected from February to April 2025, and a statistical analysis was performed using R^® statistical software for Windows, version 4.3.3. Cronbach’s alpha was tested to check internal consistency. The questionnaire was completed voluntarily and anonymously by 250 individuals who had recovered from the SARS-CoV-2 infection. The questionnaire was self-administered and had open and structured questions. Results: The highest value of Cronbach’s alpha was found on 18 items (alpha = 0.97), which means that the questionnaire has satisfactory internal validity. Conclusions: This study highlights and confirms the continuity of symptoms manifested during the acute phase of the SARS-CoV-2 infection in the post-COVID-19 phase and the significant impact of these symptoms on daily life activities. Given its excellent reliability properties and high internal consistency, the instrument is recommended for future longitudinal studies and with large cohorts in order to carry out valid and replicable measurements of COVID-19 symptomatology. Full article

The study of non-phase modulation of different frequencies in the human electroencephalography (EEG) is revealing new mechanisms involved in information processing. In particular, it has been described that the alpha band, through a desynchronization of its non-phase component, could represent a mechanism for sensory gain in visual stimulus processing. One key question to address is whether this activity can be modulated (increased) by the recall of a previously memorized stimulus. The objective of this study is to answer this question by recording EEG activity with 58 electrodes and applying time-frequency analysis techniques (Temporal Spectral Evolution and the Hilbert Transform) in a sample of 27 human participants during a word recall task. The results of the study showed an increase in alpha phase modulation for recalled words compared to not recalled words, which included modulation of the P1 component. Additionally, alpha non-phase modulation also increased for recalled words, suggesting that the enhanced P1 component response could, in fact, be an indirect result of the attenuation of background neural noise, as proposed by the sensory gain hypothesis. Full article

The burden of chronic obstructive pulmonary disease (COPD) is increasing, especially for women in low-to-middle income countries. Biomarkers provide ever-increasing diagnostic precision for COPD and show promise for primary, secondary, and tertiary disease prevention. This review describes emerging applications for biomarkers in COPD, especially as they align with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) emphasis on prevention, early diagnosis, and response to therapy. These biomarkers include blood eosinophils; IgE; C-reactive protein; fibrinogen; procalcitonin; interleukins 6, 8, and 33; tumor necrosis factor alpha; and soluble receptor for advanced glycated products (sRAGE). They have been used in various ways to identify COPD endotypes, predict exacerbations, predict mortality, and monitor the response to therapy. The fraction of exhaled nitric oxide (FENO) is increasingly studied in eosinophilic COPD endotypes and can be a diagnostic and predictive non-invasive biomarker. Imaging biomarkers, especially the quantitative computerized tomography (QCT) assessment of airway remolding, functional small airway disease, air trapping, lung function, and volume surrogates, all serve as non-invasive biomarkers for screening, early detection, and disease progression. Biomarkers facilitate all the phases of COPD care from detecting early airflow obstruction to predicting exacerbation and mortality. Biomarkers will be increasingly used as precise diagnostic tools to improve the COPD outcomes. The aim of this narrative review is to summarize the recent investigations in COPD biomarkers and their clinical applications. Full article

Emotional exhaustion in children and adolescents has become a significant concern in post-pandemic educational settings, with increased risks of anxiety, depression, and academic disengagement. Despite the growing prevalence of burnout symptoms in school-aged populations, few psychometrically validated tools exist to assess this construct in younger cohorts. This study aimed to validate the factorial structure and psychometric properties of the Emotional Exhaustion Scale (EES-CA) for use in children and adolescents, focusing on reliability, internal structure, and convergent validity. An instrumental, cross-sectional study was conducted with a sample of 543 Chilean students aged 10 to 18 (M = 13.00, SD = 1.77). The EES-CA, adapted from the university-level Emotional Exhaustion Scale, was administered along with the Depression, Anxiety, and Stress Scale (DASS-21). Data were analyzed in the following four phases: descriptive analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and convergent validity. Reliability was estimated via Cronbach’s alpha and McDonald’s omega. EFA supported the following two-factor solution: Scholar Stress and Emotional Fatigue, explaining 58.49% of the total variance. CFA confirmed the superiority of the bifactorial model (χ² = 91.74, df = 34; CFI = 0.960; RMSEA = 0.072) over the unifactorial model (χ² = 133.20, df = 35; CFI = 0.932; RMSEA = 0.093). The internal consistency was strong (α = 0.888; ω = 0.883). The convergent validity for the EES-CA showed low correlations with wellbeing (PWI) and non-significant correlations with emotional intelligence (TMMS-24), supporting discriminant validity. The EES-CA exhibits a robust bifactorial structure with high reliability and valid associations with psychological distress measures. This scale is an appropriate and psychometrically sound instrument for assessing emotional exhaustion in school-aged populations, providing a valuable tool for early detection and intervention in educational and mental health contexts. Full article