Search Results (1,544)

Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates glycolytic pathways in oncogenesis, its specific contributions to fibroblast activation and therapeutic potential in PF pathogenesis remain undefined. This study elucidates the functional role of SIK2 in PF and assesses its viability as a therapeutic target. Methods: SIK2 expression/localization in fibrosis was assessed by Western blot and immunofluorescence. Fibroblast-specific Sik2 KO mice evaluated effects on bleomycin-induced fibrosis. SIK2’s role in fibroblast activation and glucose metabolism impact (enzyme expression, metabolism assays, metabolites) were tested. SIK2 inhibitors were screened and evaluated therapeutically in fibrosis models. Results: It demonstrated significant SIK2 upregulation, specifically within activated fibroblasts of fibrotic lungs from both PF patients and murine models. Functional assays demonstrated that SIK2 is crucial for fibroblast activation, proliferation, and migration. Mechanistically, SIK2 enhances fibroblast glucose metabolism by increasing the expression of glycolysis-related enzymes. Additionally, this study demonstrated that the SIK2 inhibitor YKL06-061 effectively inhibited PF in both bleomycin and FITC-induced PF mouse models with the preliminary safety profile. Furthermore, we identified a novel therapeutic application for the clinically approved drug fostamatinib, demonstrating it inhibits fibroblast activation via SIK2 targeting and alleviates PF in mice. Conclusions: Our findings highlight SIK2 as a promising therapeutic target and provide compelling preclinical evidence for two distinct anti-fibrotic strategies with significant potential for future PF treatment. Full article

In clinical decision support systems (CDSSs), where accurate classification of drug–drug interactions (DDIs) can directly affect treatment safety and outcomes, identifying drug interactions is a major challenge, introducing a scalable approach for classifying DDIs utilizing a finely-tuned biomedical language model. The method shown here uses BiomedBERT, a domain-specific version of bidirectional encoder representations from transformers (BERT) that was pre-trained on biomedical literature, to reduce the number of resources needed during fine-tuning. Low-rank adaptation (LoRA) was used to fine-tune the model on the DrugBank dataset. The objective was to classify DDIs into two clinically distinct categories, that is, synergistic and antagonistic interactions. A pseudo-labeling strategy was created to deal with the problem of not having enough labeled data. A curated ground-truth dataset was constructed using polarity-labeled interaction entries from DrugComb and verified DrugBank antagonism pairs. The fine-tuned model is used to figure out what kinds of interactions there are in the rest of the unlabeled data. A checkpointing system saves predictions and confidence scores in small pieces, which means that the process can be continued and is not affected by system crashes. The framework is designed to log every prediction it makes, allowing results to be refined later, either manually or through automated updates, without discarding low-confidence cases, as traditional threshold-based methods often do. The method keeps a record of every output it generates, making it easier to revisit earlier predictions, either by experts or with improved tools, without depending on preset confidence cutoffs. It was built with efficiency in mind, so it can handle large amounts of biomedical text without heavy computational demands. Rather than focusing on model novelty, this research demonstrates how existing biomedical transformers can be adapted to polarity-aware DDI classification with minimal computational overhead, emphasizing deployment feasibility and clinical relevance. Full article

Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, is widely found in various consumer products and poses significant health risks, particularly through hormone receptor interactions, oxidative stress, and mitochondrial dysfunction. BPA exposure is associated with reproductive, metabolic, and neurodevelopmental disorders. Melatonin, a neurohormone with strong antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic agent to counteract the toxic effects of BPA. This review consolidates recent findings from in vitro and animal/preclinical studies, highlighting melatonin’s protective mechanisms against BPA-induced toxicity. These include its capacity to reduce oxidative stress, restore mitochondrial function, modulate inflammatory responses, and protect against DNA damage. In animal models, melatonin also mitigates reproductive toxicity, enhances fertility parameters, and reduces histopathological damage. Melatonin’s ability to regulate endoplasmic reticulum (ER) stress and cell death pathways underscores its multifaceted protective role. Despite promising preclinical results, human clinical trials are needed to validate these findings and establish optimal dosages, treatment durations, and safety profiles. This review discusses the wide range of potential uses of melatonin for treating BPA toxicity and suggests directions for future research. Full article

Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article

Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article

Medication discrepancies at hospital admission are common and may lead to adverse outcomes. Medication reconciliation is a critical process for minimizing medication discrepancies and medication errors at the time of hospital admission. This study aimed to evaluate the role of clinical pharmacists in identifying pharmacotherapy-related issues upon patient admission in a low-resource setting. A prospective observational study was conducted at a university hospital between 1 March and 31 May 2023. Within 24 h of admission, a clinical pharmacist documented each patient’s pre-admission medication regimen and compared it with the medication history obtained by the admitting physician. Discrepancies and pharmacotherapy problems were subsequently identified. Among 65 patients, pharmacists documented 334 medications versus 189 recorded by physicians (p < 0.01). The clinical pharmacist identified 155 discrepancies, 112 (72.26%) of which were unintentional. The most frequent type was drug omission (91.07%), followed by incorrect dosage (4.46%), incorrect dosing interval (2.68%), and medications with unknown indications (1.79%). Most discrepancies were classified as errors without harm (53.57%), while 41.07% were potentially harmful. These findings underscore the importance of integrating clinical pharmacists into the healthcare team. Their active participation during hospital admission can significantly enhance medication safety and reduce preventable adverse drug events. Full article

Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Aims/Background: Polypharmacy, or the concurrent intake of five or more medications, is a significant issue in clinical practice, particularly in multimorbid elderly individuals. Despite its importance for patient safety, medical education often lacks systematic training in recognising and managing polypharmacy within the framework of patient-centred care. We investigated the impact of a structured learning intervention introducing polypharmacy as a chronic condition, assessing whether it enhances medical students’ diagnostic competence, confidence, and interprofessional collaboration. Methods: A prospective cohort study was conducted with 50 final-year medical students who received a three-phase educational intervention. Phase 1 was interactive workshops on the principles of polypharmacy, its dangers, and diagnostic tools. Phase 2 involved simulated patient consultations and medication review exercises with pharmacists. Phase 3 involved reflection through debriefing sessions, reflective diaries, and standardised patient feedback. Student knowledge, confidence, and attitudes towards polypharmacy management were assessed using pre- and post-intervention questionnaires. Quantitative data were analysed through paired t-tests, and qualitative data were analysed thematically from reflective diaries. Results: Students demonstrated considerable improvement after the intervention in identifying symptoms of polypharmacy, suggesting deprescribing strategies, and working in multidisciplinary teams. Confidence in prioritising polypharmacy as a primary diagnostic problem increased from 32% to 86% (p < 0.01), and knowledge of diagnostic tools increased from 3.1 ± 0.6 to 4.7 ± 0.3 (p < 0.01). Standardised patients felt communication and patient-centredness had improved, with satisfaction scores increasing from 3.5 ± 0.8 to 4.8 ± 0.4 (p < 0.01). Reflective diaries indicated a shift towards more holistic thinking regarding medication burden. The small sample size limits the generalisability of the results. Conclusions: Teaching polypharmacy as a chronic condition in medical school enhances diagnostic competence, interprofessional teamwork, and patient safety. Education is a structured way of integrating the management of polypharmacy into routine clinical practice. This model provides valuable insights for designing medical curricula. Future research must assess the impact of such training on patient outcomes and clinical decision-making in the long term. Full article

Introduction: Given the impact of aneurysmal subarachnoid hemorrhage (aSAH) on patients’ health, preclinical research is substantial to understand its pathophysiology and improve treatment strategies, which necessitates reliable and comprehensive animal models. Traditionally, aSAH models utilize iliac or subclavian access for angiography, requiring invasive procedures that are associated with significant risks and animal burden. This pilot study explores a less invasive method of digital subtraction angiography (DSA) by using the auricular artery (AA) as an alternative access point. Our aim was to demonstrate the feasibility of this refined technique, with the intention of reducing procedural risks, providing shorter operation times with enhanced neurological recovery, and simplifying the process for both researchers and animals. Materials and Methods: In this study, six female New Zealand white rabbits (3.2–4.1 kg body weight) underwent experimental induction of aSAH via a subclavian-cisternal shunt. The initial steps of this procedure followed traditional techniques, consisting of subclavian access through microsurgical preparation, followed by DSA to analyze retrograde filling of the basilar artery (BA). To evaluate the alternative method, on day 3 after induction of aSAH, DSA was performed via the AA instead of the traditional subclavian or femoral access. A catheter was placed in the AA to allow retrograde filling of the BA. This approach aimed to simplify the procedure while maintaining comparable imaging quality. Results: All rabbits survived until the study endpoint. Postoperatively, two rabbits showed signs of hemisyndrome, which significantly improved by the time of follow-up. No additional morbidities were observed. Upon euthanasia and necropsy, all animals showed clear subarachnoid bleeding patterns. DSA via the AA produced strong contrasting of the BA comparable to the traditional method. Conclusions: This technical note presents an initial evaluation of AA access as a feasible and potentially advantageous method for DSA in a rabbit model of blood shunt subarachnoid hemorrhage. The method shows promise in reducing invasiveness and procedural complexity, but further studies are required to fully establish its efficacy and safety. Future research should focus on expanding the sample size, refining the anatomical understanding of the AA, and continuing to align with ethical considerations regarding animal welfare. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders. Full article

High-Intensity Focused Ultrasound (HIFU) is a non-invasive technology widely used in aesthetic dermatology for skin tightening and facial rejuvenation. This study aimed to evaluate the safety and efficacy of a modified HIFU device, More Young, compared to the standard 7D HIFU system through a randomized, single-blinded clinical trial. The More Young device features enhanced focal depth precision and energy delivery algorithms, including nine pre-programmed stabilization checkpoints to minimize treatment risks. A total of 100 participants with facial wrinkles and skin laxity were randomly assigned to receive either More Young or 7D HIFU treatment. Skin improvements were assessed at baseline and one to six months post-treatment using the VISIA^® Skin Analysis System (7th Generation), focusing on eight key parameters. Patient satisfaction was evaluated through the Global Aesthetic Improvement Scale (GAIS). Data were analyzed using paired and independent t-tests, with effect sizes measured via Cohen’s d. Both groups showed significant post-treatment improvements; however, the More Young group demonstrated superior outcomes in wrinkle reduction, skin tightening, and texture enhancement, along with higher satisfaction and fewer adverse effects. No significant differences were observed in five of the eight skin parameters. Limitations include the absence of a placebo group, limited sample diversity, and short follow-up duration. Further studies are needed to validate long-term outcomes and assess performance across varied demographics and skin types. Full article

Surgery remains a healthcare intervention with significant risks for patients. Novel technologies can now enhance the peri-operative workflow, with artificial intelligence (AI) and extended reality (XR) to assist with pre-operative planning. This review focuses on innovation in AI, XR and imaging for hepato-biliary surgery planning. The clinical challenges in hepato-biliary surgery arise from heterogeneity of clinical presentations, the need for multiple imaging modalities and highly variable local anatomy. AI-based models have been developed for risk prediction and multi-disciplinary tumor (MDT) board meetings. The future could involve an on-demand and highly accurate AI-powered decision tool for hepato-biliary surgery, assisting the surgeon to make the most informed decision on the treatment plan, conferring the best possible outcome for individual patients. Advances in AI can also be used to automate image interpretation and 3D modelling, enabling fast and accurate 3D reconstructions of patient anatomy. Surgical navigation systems utilizing XR are already in development, showing an early signal towards improved patient outcomes when used for hepato-biliary surgery. Live visualization of hepato-biliary anatomy in the operating theatre is likely to improve operative safety and performance. The technological advances in AI and XR provide new applications in pre-operative planning with potential for patient benefit. Their use in surgical simulation could accelerate learning curves for surgeons in training. Future research must focus on standardization of AI and XR study reporting, robust databases that are ethically and data protection-compliant, and development of inter-disciplinary tools for various healthcare applications and systems. Full article

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article