Search Results (11,314)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for Magnetic Resonance Imaging (MRI) has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for the diagnosis and treatment of patients with various cancers, the detection of PDAC remains challenging. Nevertheless, recent advancements in PDAC theranostics provided progress in the detection and treatment of this challenging type of cancer. Present research in this area is focused on suitable carriers, eliminating delivery barriers, and the development of efficient anti-cancer drugs. Herein we discuss the current applications of iron oxide nanoparticles to the MRI diagnosis and treatment of pancreatic cancer. Full article

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article

Background and Objectives: Periodontitis is a chronic inflammatory disease that leads to progressive destruction of periodontal tissues and remains a significant global health burden. While conventional therapies such as scaling and root planning offer short-term improvements, they often fall short in maintaining long-term microbial control, underscoring the need for adjunctive strategies. This study evaluated the clinical and microbiological effects of a novel essential oil (EO)-based gel—SmartGel OV—formulated with Origanum vulgare. Materials and Methods: Thirty adults with periodontitis were enrolled in a 4-month observational study, during which SmartGel OV was applied daily via gingival massage. Clinical outcomes and bacterial profiles were assessed through probing measurements and real-time PCR analysis. Additionally, a pilot AI-based tool was explored as a supplemental method to monitor inflammation progression through intraoral images. Results: Significant reductions were observed in Fusobacterium nucleatum and Capnocytophaga spp., accompanied by improvements in clinical markers, including probing depth, bleeding on probing, and plaque index. The AI framework successfully identified visual inflammation changes and supported early detection of non-responsiveness. Conclusions: SmartGel OV demonstrates promise as a natural adjunctive treatment for periodontitis and AI monitoring was included as an exploratory secondary tool to assess feasibility for future remote tracking. Full article

Corneal diseases are among the leading causes of blindness worldwide and the standard treatment is the transplantation of corneal donor tissue. Treatment for cornea-related visual impairment and blindness is, however, often constrained by the global shortage of suitable donor grafts. To alleviate the shortage of corneal donor tissue, new treatment options have been explored in the last decade. The discovery of induced pluripotent stem cells (iPSCs), which has revolutionized regenerative medicine, offers immense potential for corneal repair and regeneration. Using iPSCs can provide a renewable source for generating various corneal cell types, including corneal epithelial cells, stromal keratocytes, and corneal endothelial cells. To document the recent progress towards the clinical application of iPSC-derived corneal cells, this review summarizes the latest advancements in iPSC-derived corneal cell therapies, ranging from differentiation protocols and preclinical studies to the first clinical trials, and discusses the challenges for successful translation to the clinic. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Organoids allow to model healthy and diseased human tissues. and have applications in developmental biology, drug discovery, and cell therapy. Traditionally cultured in immersion/suspension, organoids face issues like lack of standardization, fusion, hypoxia-induced necrosis, continuous agitation, and high media volume requirements. To address these issues, we developed an air–liquid interface (ALi) technology for culturing organoids, termed AirLiwell. It uses non-adhesive microwells for generating and maintaining individualized organoids on an air–liquid interface. This method ensures high standardization, prevents organoid fusion, eliminates the need for agitation, simplifies media changes, reduces media volume, and is compatible with Good Manufacturing Practices. We compared the ALi method to standard immersion culture for midbrain organoids, detailing the process from human pluripotent stem cell (hPSC) culture to organoid maturation and analysis. Air–liquid interface organoids (3D-ALi) showed optimized size and shape standardization. RNA sequencing and immunostaining confirmed neural/dopaminergic specification. Single-cell RNA sequencing revealed that immersion organoids (3D-i) contained 16% fibroblast-like, 23% myeloid-like, and 61% neural cells (49% neurons), whereas 3D-ALi organoids comprised 99% neural cells (86% neurons). Functionally, 3D-ALi organoids showed a striking electrophysiological synchronization, unlike the heterogeneous activity of 3D-i organoids. This standardized organoid platform improves reproducibility and scalability, demonstrated here with midbrain organoids. The use of midbrain organoids is particularly relevant for neuroscience and neurodegenerative diseases, such as Parkinson’s disease, due to their high incidence, opening new perspectives in disease modeling and cell therapy. In addition to hPSC-derived organoids, the method’s versatility extends to cancer organoids and 3D cultures from primary human cells. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

In the original randomised Dietary Intervention to Stop Coronary Atherosclerosis (DISCO-CT) trial, a 12-month Dietary Approaches to Stop Hypertension (DASH) project led by dietitians improved cardiovascular and metabolic risk factors and reduced platelet chemokine levels in patients with coronary artery disease (CAD). It is unclear whether these benefits are sustained. Objective: To determine whether the metabolic, inflammatory, and clinical benefits achieved during the DISCO-CT trial are sustained six years after the structured intervention ended. Methods: Ninety-seven adults with non-obstructive CAD confirmed in coronary computed tomography angiography were randomly assigned to receive optimal medical therapy (control group, n = 41) or the same therapy combined with intensive DASH counselling (DASH group, n = 43). After 301 ± 22 weeks, 84 individuals (87%) who had given consent underwent reassessment of body composition, meal frequency assessment, and biochemical testing (lipids, hs-CRP, CXCL4, RANTES and homocysteine). Major adverse cardiovascular events (MACE) were assessed. Results: During the intervention, the DASH group lost an average of 3.6 ± 4.2 kg and reduced their total body fat by an average of 4.2 ± 4.8 kg, compared to an average loss of 1.1 ± 2.9 kg and a reduction in total body fat of 0.3 ± 4.1 kg in the control group (both p < 0.01). Six years later, most of the lost body weight and fat tissue had been regained, and there was a sharp increase in visceral fat area in both groups (p < 0.0001). CXCL4 decreased by 4.3 ± 3.0 ng/mL during the intervention and remained lower than baseline values; in contrast, in the control group, it initially increased and then decreased (p < 0.001 between groups). LDL cholesterol and hs-CRP levels returned to baseline in both groups but remained below baseline in the DASH group. There was one case of MACE in the DASH group, compared with four cases (including one fatal myocardial infarction) in the control group (p = 0.575). Overall adherence to the DASH project increased by 26 points during counselling and then decreased by only four points, remaining higher than in the control group. Conclusions: A one-year DASH project supported by a physician and dietitian resulted in long-term suppression of the proatherogenic chemokine CXCL4 and fewer MACE over six years, despite a decline in adherence and loss of most anthropometric and lipid benefits. It appears that sustained systemic reinforcement of behaviours is necessary to maintain the benefits of lifestyle intervention in CAD. Full article

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [¹⁸F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment. Full article

Despite advances in medicine, cancer remains one of the foremost global health concerns. Conventional treatments like surgery, radiotherapy, and chemotherapy have advanced with the emergence of targeted and immunotherapy approaches. However, therapeutic resistance and relapse remain major barriers to long-term success in cancer treatment, often driven by cancer stem cells (CSCs). These rare, resilient cells can survive therapy and drive tumour regrowth, urging deeper investigation into the mechanisms underlying their persistence. CSCs express ion channels typical of excitable tissues, which, beyond electrophysiology, critically regulate CSC fate. However, the underlying regulatory mechanisms of these channels in CSCs remain largely unexplored and poorly understood. Nevertheless, the therapeutic potential of targeting CSC ion channels is immense, as it offers a powerful strategy to disrupt vital signalling pathways involved in numerous pathological conditions. In this review, we explore the diverse repertoire of ion channels expressed in CSCs and highlight recent mechanistic insights into how these channels modulate CSC behaviours, dynamics, and functions. We present a concise overview of ion channel-mediated CSC regulation, emphasizing their potential as novel diagnostic markers and therapeutic targets, and identifying key areas for future research. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article