Search Results (4,255)

This study presents the development of an advanced three-dimensional (3D) bioprinted skin scaffold integrating sodium alginate (SA), gelatin (Gel), human skin-derived decellularized extracellular matrix (dECM), and microbiota-derived postbiotics. To ensure a biocompatible and functional ECM source, human skin samples collected during elective aesthetic surgical procedures were utilized. Following enzymatic treatment, the dermal layer was carefully separated from the epidermis and subjected to four different decellularization protocols. Among them, Protocol IV emerged as the most suitable, achieving significant DNA removal while maintaining the structural and biochemical integrity of the ECM, as confirmed by Fourier-transform infrared spectroscopy. Building on this optimized dECM-4, microbiota-derived postbiotics from Limosilactobacillus reuteri EIR/Spx-2 were incorporated to further enhance the scaffold’s bioactivity. Hybrid scaffolds were then fabricated using 7% Gel, 2% SA, 1% dECM-4, and 40 mg/mL postbiotics in five-layered grid structures via 3D bioprinting technology. Although this composition resulted in reduced mechanical strength, it exhibited improved hydrophilicity and biodegradability. Moreover, antimicrobial assays demonstrated inhibition zones of 16 mm and 13 mm against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) and Pseudomonas aeruginosa (ATCC 27853), respectively. Importantly, biocompatibility was confirmed through in vitro studies using human keratinocyte (HaCaT) cells, which adhered, proliferated, and maintained normal morphology over a 7-day culture period. Taken together, these findings suggest that the engineered hybrid scaffold provides both regenerative support and antimicrobial protection, making it a strong candidate for clinical applications, particularly in the management of chronic wounds. Full article

This study investigates the comparative performance of foundational models, advanced large-kernel architectures, and traditional deep learning approaches for hyperpolarized gas MRI segmentation across progressive data reduction scenarios. Chronic obstructive pulmonary disease (COPD) remains a leading global health concern, and advanced imaging techniques are crucial for its diagnosis and management. Hyperpolarized gas MRI, utilizing helium-3 (³He) and xenon-129 (¹²⁹Xe), offers a non-invasive way to assess lung function. We evaluated foundational models (Segment Anything Model and MedSAM), advanced architectures (UniRepLKNet and TransXNet), and traditional deep learning models (UNet with VGG19 backbone, Feature Pyramid Network with MIT-B5 backbone, and DeepLabV3 with ResNet152 backbone) using four data availability scenarios: 100%, 50%, 25%, and 10% of the full training dataset (1640 2D MRI slices from 205 participants). The results demonstrate that foundational and advanced models achieve statistically equivalent performance across all data scenarios (p > 0.01), while both significantly outperform traditional architectures under data constraints (p < 0.001). Under extreme data scarcity (10% training data), foundational and advanced models maintained DSC values above 0.86, while traditional models experienced catastrophic performance collapse. This work highlights the critical advantage of architectures with large effective receptive fields in medical imaging applications where data collection is challenging, demonstrating their potential to democratize advanced medical imaging analysis in resource-limited settings. Full article

Flexible and wearable sensors have emerged as transformative technologies in the field of real-time health monitoring, offering non-invasive, continuous, and personalized healthcare solutions. These devices are designed to conform intimately to the human body, enabling seamless detection of vital physiological and biochemical signals under dynamic conditions. Recent advancements in material science and device engineering have led to the development of sensors with enhanced sensitivity, biocompatibility, and wearability, addressing the growing demand for preventive healthcare and remote patient monitoring. This review provides a comprehensive overview of the progress in flexible wearable sensors, including novel materials, sensor designs, and system integration strategies. It begins by surveying the latest advances in substrate and functional materials and hybrid structures that enable mechanical flexibility, skin conformability, and high sensitivity. The review then examines various sensor mechanisms and their implementation in monitoring vital signs, physical activity, and chronic diseases. Real-world applications are explored in depth, covering scenarios from cardiovascular and respiratory monitoring to motion tracking and rehabilitation support. Despite the significant strides made, challenges related to material robustness, sensor accuracy, and multi-modal integration remain, and this review discusses these challenges alongside potential future directions for enhancing the functionality and adoption of flexible wearable sensor systems. Full article

Aging results from the combined effects of oxidative stress, chronic low-grade inflammation, mitochondrial decline, and cellular senescence, which together drive age-related disorders. Natural products ranging from polyphenols and terpenoids to alkaloids, polysaccharides, peptides, and marine metabolites can influence central pathways such as Nrf2/ARE, NF-κB, MAPK, JAK/STAT, AMPK/PGC1-α, mTOR, and SIRT1/FOXO. By doing so, they strengthen antioxidant defenses, temper inflammation, preserve mitochondrial balance, and regulate autophagy. Increasing attention is also being given to synergy, where combinations of bioactives can achieve stronger and more balanced effects than single agents alone. Advances in artificial intelligence are accelerating this discovery process, while greener extraction and smarter delivery systems such as deep eutectic solvents and nanostructured carriers are improving bioavailability and consistency. Together, these developments underscore the promise of natural product-based strategies for healthy aging. Grounded in rigor and reproducibility, this Special Issue aims to inspire translational advances toward healthier and more graceful aging. Full article

Glaucoma is a chronic, progressive optic neuropathy characterized by the degeneration of retinal ganglion cells. It is one of the leading causes of blindness worldwide, with elevated intraocular pressure (IOP) being the most significant modifiable risk factor. The objective of this paper is to assess the effectiveness of Direct Selective Laser Trabeculoplasty (DSLT) in the management of glaucoma and OHT based on analysis of available literature. Topical hypotensive medications are the preferred first-line therapy for both newly diagnosed open angle glaucoma (OAG) and ocular hypertension (OHT) over other treatment modalities for most patients. Medical glaucoma management, despite proven efficacy, is limited by issues of patient adherence, quality-of-life decrease, side effects, and ocular surface disease (OSD). Selective Laser Trabeculoplasty (SLT) has emerged as a safe, effective, and repeatable alternative to medical therapy for patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Direct Selective Laser Trabeculoplasty (DSLT) is a novel, non-contact laser treatment that delivers energy transsclerally to the trabecular meshwork (TM) without the use of a gonioscope. In recent studies, DSLT has demonstrated comparable efficacy to conventional SLT, including the multicenter randomized GLAUrious trial. It reduces IOP by 18–27%, often enabling reduction in or discontinuation of hypotensive topical medications. The non-contact, automated nature of DSLT simplifies the procedure, enhances patient comfort, and may expand access to laser therapy across diverse clinical settings. In conclusion, DSLT represents an innovative advancement in laser therapy for glaucoma, combining the clinical benefits of SLT with enhanced procedural efficiency and safety. Further long-term studies are needed to validate its durability, but existing evidence supports its use as a first-line or adjunctive treatment for OAG and OHT. Full article

Background: The consequences of median nerve compression at the carpal tunnel level require a precise diagnostic evaluation before a frequently applied surgical intervention. Positive Tinel or Phalen signs are not always related to abnormal results in electroneurographic examinations of sensory and motor nerve fibers, which are intended to confirm final diagnoses, thereby confusing both surgeons and neurophysiologists. In the face of contradictory data, this study aims to reinvestigate these correlations in a randomly chosen population of patients with a primary diagnosis of carpal tunnel syndrome (CTS). Methods: Seventy-five randomly chosen patients with clinically detected CTS underwent neurophysiological studies of median nerve sensory (SNAP) and motor (CMAP) fibers conduction at the wrist. Both the median and ulnar nerves were assessed to reduce the risk of misinterpretation related to anatomical variations. Results: This study provides evidence on the relatively high utility of Phalen’s test in the early clinical detection of CTS within a general population of patients, whose positive results moderately correlate (rho = −0.327) with abnormalities in amplitudes rather than the distal latency parameters of SNAP recordings. The axonal injury type is more distinct than slowing-down impulses at the wrist following compression of the sensory nerve fibers in the early course of CTS. Positive Tinel’s test results are useful in diagnosing CTS patients with advanced axonal and demyelinating changes in the motor fibers at the wrist, which weakly correlate with prolonged latency and decreased amplitude in SNAP recordings (rho = −0.214 and rho = −0.235, respectively), but not with abnormalities in recordings of both amplitudes and latencies in CMAP electroneurography. Conclusions: The correlations between clinical signs and neurophysiological findings in CTS indicate that provocative tests, such as Phalen’s and Tinel’s, have limited diagnostic value, demonstrating only weak-to-moderate associations with neural conduction parameters. A positive Tinel’s sign should be regarded mainly as a marker of severe or chronic sensory impairment, often accompanied by motor fibers involvement in advanced pathological stages, rather than as an indicator of motor damage alone. Nerve conduction studies remain essential for confirming CTS, assessing its severity, and guiding treatment decisions, including surgical qualification. The presented correlation of clinical and functional neurophysiological results in CTS diagnosis allows us not only to specify the source and severity of the pathology of the median nerve fibers but also may influence the personalization of physiotherapeutic and surgical treatments. Full article

Right heart failure (RHF) remains an under-recognized yet devastating condition in critically ill and chronic patients, frequently complicating cardiac surgery, pulmonary embolism, advanced heart failure, sepsis and left ventricular assist device (LVAD) implantation. Despite growing awareness, clinical decision making is still hampered by the complex pathophysiology, limitations in diagnosis and a fragmented therapeutic landscape. In recent years, progress in hemodynamic phenotyping, advanced echocardiographic and biomarker-based assessment, and the development of mechanical circulatory support (MCS) systems, including percutaneous and surgical right ventricle assist devices (RVAD), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), Impella RP (right percutaneous) or BiPella (Impella CP/5.0/5.5 + Impella RP) has expanded the armamentarium for managing RHF. This review synthetizes current evidences on the anatomical, physiological and molecular underpinnings of RHF, delineates the distinction and continuum between acute and chronic forms and provides a comparative analysis of diagnostic tools and MCS strategies. By integrating mechanistic insights with emerging clinical frameworks, the review aims to support earlier recognition, tailored management and innovative therapeutic approaches for this high-risk population. Full article

Reactive oxygen species (ROS) function as critical signaling molecules in cancer biology, promoting proliferation, angiogenesis, and metastasis at controlled levels while inducing lethal damage when exceeding the cell’s buffering capacity. To survive under this state of chronic oxidative stress, cancer cells become dependent on a hyperactive antioxidant shield, primarily orchestrated by the Nrf2, glutathione (GSH), and thioredoxin (Trx) systems. These defenses maintain redox homeostasis and sustain oncogenic signaling, notably through the oxidative inactivation of tumor-suppressor phosphatases, such as PTEN, which drives the PI3K/AKT/mTOR pathway. Targeting this addiction to a rewired redox state has emerged as a compelling therapeutic strategy. Pro-oxidant therapies aim to overwhelm cellular defenses, with agents like high-dose vitamin C and arsenic trioxide (ATO) showing significant tumor-selective toxicity. Inhibiting the master regulator Nrf2 with compounds such as Brusatol or ML385 disrupts the core antioxidant response. Disruption of the GSH system by inhibiting cysteine uptake with sulfasalazine or erastin potently induces ferroptosis, a non-apoptotic cell death driven by lipid peroxidation. Furthermore, the thioredoxin system is targeted by the repurposed drug auranofin, which irreversibly inhibits thioredoxin reductase (TrxR). Extensive preclinical data and ongoing clinical trials support the concept that this reliance on redox adaptation is a cancer-selective vulnerability. Moreover, novel therapeutic strategies, including the expanding field of redox-active metal complexes, such as manganese porphyrins, which strategically leverage the differential redox state of normal versus cancer cells through both pro-oxidant and indirect Nrf2-mediated antioxidative mechanisms (triggered by Keap1 oxidation), with several agents currently in advanced clinical trials, have also been discussed. Essentially, pharmacologically tipping the redox balance beyond the threshold of tolerance offers a rational and powerful approach to eliminate malignant cells, defining a novel frontier for targeted cancer therapy. Full article

Background and Clinical Significance: Advanced pelvic organ prolapse (POP) associated with perineal herniation of pelvic and abdominal organs is a sporadic occurrence in gynaecological practice. Generally, POP affects up to 50% of multiparous women at some point during their lives. Advanced forms (grade III or IV) represent less than 10% of all cases, with severe grade IV prolapse occurring in fewer than 2% of patients. Case Presentation: We report the case of a 48-year-old nulliparous woman with no prior surgical history and no known medical conditions at presentation. The patient presented with severe grade IV POP (Baden–Walker Classification), characterised by abdominal pain, vaginal bleeding and significant urinary incontinence. A computed tomography scan was performed, revealing an extremely large perineal hernia, containing the uterus, urinary bladder, and small bowel loops—a rare finding with only isolated cases reported in the medical literature. Surgical treatment involved a total intracapsular hysterectomy with right-sided adnexectomy and colpoperineorrhaphy. After the surgery, the overall status of the patient was good. However, less than two months later, she returned, complaining of a recurrence of the initial pathology, and was diagnosed with grade II/III POP recurrence despite having no connective tissue disorders or other classical predisposing factors such as pregnancies, pelvic surgery history or obstetric trauma. The case was further complicated by a femoral neck fracture, stage V chronic kidney disease, COVID-19 pneumonia, and a Clostridium difficile infection. All these complications led to the postponement of the gynaecological reintervention procedure. Conclusions: We emphasise the significant challenges in managing this kind of perineal hernia, under unusual conditions and without common risk factors. A personalised, multidisciplinary approach is required, including careful follow-up to prevent early recurrence. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) face higher risks of infections, poor vaccine responses, and cardiovascular diseases, leading to increased morbidity and mortality due to immune dysfunction and frailty. This study aims to evaluate immune status and frailty in CKD patients across different treatments, examine the influence of frailty on immune status, and link these factors to mortality. Methods: A total of 174 participants were included (end-stage renal disease, ESRD n = 40; hemodialysis, HD n = 40; peritoneal dialysis, n = 36; kidney transplant patients, n = 40; healthy subjects n = 18). Immunophenotyping of lymphocyte and monocyte subpopulations was performed, and frailty was assessed using the Edmonton Frail Scale. Principal component analysis (PCA) integrated immune and frailty variables to define an “immuno-fragile profile,” and survival was monitored for up to six years. Results: CKD patients, especially those on HD, showed decreased lymphocyte counts and proinflammatory monocyte subpopulations with increased expression of costimulatory molecules (B7.2/CD86 and ICAM-1/CD54). Frailty was most prevalent in HD patients (53%), with notable sex differences. PCA identified three components—lymphocyte counts, monocyte co-stimulatory expression, and frailty—that together explained 70% of the variance. Survival analysis revealed that patients with lower lymphocyte counts and higher frailty scores had increased mortality risk, especially in the HD and ESRD groups. Cox regression confirmed that the immuno-fragile profile independently predicted mortality. Conclusions: The integration of immune alterations and frailty defines an immuno-fragile profile strongly associated with mortality in CKD patients, which may serve as a robust prognostic tool to improve risk stratification and guide personalized interventions in clinical practice. Full article

Background/Objectives: Despite recent therapeutic advances, the clinical management of renal cell carcinoma (RCC) remains suboptimal. Current treatments are hindered by limited efficacy, the emergence of acquired drug resistance, suboptimal tolerability, and a lack of tumor-specific targeting. While development of novel agents remains an important avenue, it is often constrained by high costs, long development time, and low success rates. As an alternative approach, drug combinations of approved agents offer a promising strategy. Methods: Using our proprietary drug combination methodology, we identified multidrug combinations in RCC cells representing the clear cell (786O) and sarcomatoid chromophobe (UOK276) histological subtypes of RCC. Results: From an initial panel of 10 drugs, either approved or undergoing clinical trial, the optimized drug combinations (ODCs) contained crizotinib, telaglenastat, U-104, and vismodegib at clinical and subtherapeutic doses. The ODCs were non-toxic in advanced hepatic, renal, and cardiac cellular models. Importantly, their anti-tumor activity, already notable in normoxic (21% O₂) conditions (approx. 50%) was markedly enhanced in tumor-relevant hypoxia (1.5% O₂), reaching up to 77% in 2D and 62% in 3D spheroid 786O models. Moreover, chronic exposure of 786O and UOK276 cells led to durable responses, suggesting a prolonged effect in responders. Conclusions: Our findings demonstrate the potential of optimized, non-toxic drug combinations as a highly selective and effective strategy for accelerating the development of precision RCC treatment. Full article

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management and has been shown to exert cardioprotective and antioxidant effects. This study aimed to evaluate whether Lir mitigates hyperglycemia-induced oxidative and hypoxic stress in H9c2 cardiomyoblasts while preserving cellular ultrastructure. Materials and Methods: H9c2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions, with or without Lir. Cell viability was assessed using MTT assay. Ultrastructural changes were examined by transmission electron microscopy (TEM). Hypoxia-inducible factor-1α (HIF-1α), lipid peroxidation markers (LOOH, MDA), advanced oxidation protein products (AOPP), and total antioxidant capacity (TAC) were quantified by spectrophotometric assays. Results: MTT assays revealed that Lir significantly improved cell viability under hyperglycemic conditions and the EC₅₀ was 1.05 ± 0.06 μM after 48 h of treatment. Under HG, HIF-1α, lipid hydroperoxides (LOOH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) increased and total antioxidant capacity (TAC) decreased (p < 0.001, for all); Lir significantly reversed these changes, restoring values to near-NG levels. Ultrastructural analysis of HG + Lir-treated cells revealed reduced granules, increased vacuolization, and slight rough endoplasmic reticulum dilatation, though mitochondria appeared normal. Conclusions: Lir significantly attenuated oxidative stress and cellular injury in cardiomyocytes under hyperglycemic conditions, improving viability, modulating HIF-1α expression, and restoring antioxidant balance. These findings support a dual role for Lir in diabetic cardiomyopathy: glucose-independent cytoprotection and regulation of mitochondrial and hypoxia pathways, highlighting its therapeutic potential beyond glycemic control. Full article

Despite the widespread use of dithiocarbamate fungicides such as maneb, mancozeb, metiram, propineb, thiram, and ziram detected, according to EU legislation, via common degradation product carbon disulfide (CS₂), recent and comprehensive reviews on analytical methods for their determination in plant-based foods are lacking. Given the well-documented toxicity shown by the experimental model for these pesticides, including neurotoxicity and endocrine disruption, harmonized and reliable analytical protocols are crucial for food safety monitoring and regulatory compliance. Dithiocarbamates, beyond CS₂ release, have been associated with immunotoxicity, thyroid dysfunction, and potential carcinogenicity, raising further concern regarding chronic dietary exposure. Their metabolites may disrupt enzymatic activity and oxidative balance, enhancing systemic toxicity. Early methods, had limited sensitivity, poor reproducibility, and relied on hazardous solvents, reducing practical value. Although later advancements improved detection limits, modern procedures, including those proposed by the European Union Reference Laboratory (EURL), still show limitations. The EURL-recommended protocol involves acid hydrolysis using concentrated HCl, extraction with isooctane, heating to 85 °C, and rapid ice-bath cooling, which poses environmental concerns. Recovery efficiency remains inconsistent in some cases, and reproducibility within commodity groups is poor. This review discusses the status of methods for determining dithiocarbamates as individual compounds and via CS₂ moiety. Full article

Repairing the central nervous system (CNS) remains one of the most difficult obstacles to overcome in translational neurosciences. This is due to intrinsic growth inhibitors, extracellular matrix issues, the glial scar–form barrier, chronic neuroinflammation, and epigenetic silencing. The purpose of this review is to bring together findings from recent developments in genome editing and computational approaches, which center around the possible convergence of clustered regularly interspaced short palindromic repeats (CRISPR) platforms and artificial intelligence (AI), towards precision neuroregeneration. We wished to outline possible ways in which CRISPR-based systems, including but not limited to Cas9 and Cas12 nucleases, RNA-targeting Cas13, base and prime editors, and transcriptional regulators such as CRISPRa/i, can be applied to potentially reactivate axon-growth programs, alter inhibitory extracellular signaling, reprogram or lineage transform glia to functional neurons, and block oncogenic pathways in glioblastoma. In addition, we wanted to highlight how AI approaches, such as single-cell multi-omics, radiogenomic prediction, development of digital twins, and design of adaptive clinical trials, will increasingly be positioned to act as system-level architects that allow translation of complex datasets into predictive and actionable therapeutic approaches. We examine convergence consumers in spinal cord injury and adaptive neuro-oncology and discuss expanse consumers in ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and rare neurogenetic syndromes. Finally, we discuss the ethical and regulatory landscape around beyond off-target editing and genomic stability of CRISPR, algorithmic bias, explainability, and equitable access to advanced neurotherapies. Our intent was not to provide a comprehensive inventory of possibilities but rather to provide a conceptual tool where CRISPR acts as a molecular manipulator and AI as a computational integrator, converging to create pathways towards precision neuroregeneration, personalized medicine, and adaptive neurotherapeutics that are ethically sound. Full article