Search Results (107,896)

Background: Photothermal therapy (PTT), a highly efficient and controllable method with minimal drug resistance, transforms near-infrared (NIR) radiation into heat. This process exerts antibacterial effects, aids in tissue repair, and promotes healing. Methods: Our study presented a novel kind of composite wound dressing that incorporated adhesive conductive hydrogel combined with piezoelectric film for NIR-responsive applications. The inherent adhesiveness of the hydrogel ensured robust anchoring of the piezoelectric film to both hydrogel matrix and wound site. Its conductivity enabled synergistic endogenous electrical stimulation with the piezoelectric film, while also serving as therapeutic layer to augment hemostasis, analgesia, and antibacterial activity. Results: The hydrogel’s capacity for moisture retention and exudate absorption sustained optimal wound environment, thereby supporting debridement and recovery. Furthermore, the piezoelectric film possessed excellent photothermal properties and transferred heat to the hydrogel through heat conduction to enhance antibacterial activity and promote wound healing. The in vitro and ins vivo experiments confirmed that the composite dressing exhibited strong promotion effect on wound healing under NIR irradiation. Conclusions: In summary, our research provided a new strategy for developing advanced piezoelectric biomaterials with great clinical potential for wound healing. Full article

Background: Bayesian model-informed precision dosing (MIPD) is increasingly used to individualize drug therapy; therefore, this review aimed to identify and characterize its implementation in routine clinical practice. Methods: A focused systematic review was conducted. Web of Science Core Collection and PubMed were searched from inception to February 2026. Eligible studies were original research articles evaluating Bayesian MIPD in routine clinical practice using software platforms that supported dosing decisions. Data were synthesized descriptively. No formal risk-of-bias assessment was performed due to heterogeneity in study design. Results: Fifteen studies met the inclusion criteria. Anti-infective therapy predominated, particularly vancomycin (n = 11), with additional studies involving busulfan, mycophenolate mofetil, amikacin, and tobramycin. Commonly reported software platforms included InsightRx (n = 6) and DoseMeRx (n = 4), along with Abbottbase, NextDose, and ISBA. MIPD was mainly applied with therapeutic drug monitoring, reflecting predominant a posteriori use in routine care. Across studies, implementation was associated with improved pharmacokinetic target attainment, while a subset reported clinical benefits, including reduced nephrotoxicity and favorable effectiveness-related outcomes. Pharmacist involvement was commonly described. Conclusions: Published evidence indicates that Bayesian MIPD is being implemented in routine clinical settings, but current published experience is dominated by vancomycin-focused studies. Although the evidence base remains limited, it has grown since 2020 and suggests that software-supported Bayesian dosing can improve pharmacokinetic target attainment and may support better clinical outcomes. Full article

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although external factors drive rich metabolite diversity, continual variation can also lead to translational constraints including heavy-metal accumulation, inconsistency in extract composition, and regulatory complexity. This review examines the environmental drivers of metabolite diversity and the functional potential of bioactives derived from marine algae. We focus on their translational application within four areas of growing interest: nutraceuticals, cosmetics, regenerative medicine, and oncology, where emerging evidence suggests their promise as next-generation bioactive ingredients and therapeutic leads. In addition, insights from Irish and Welsh Small and Medium Enterprises (SMEs) are collated to identify key bottlenecks in commercialisation and the requirements for effective marine biodiscovery pipelines. We consider the importance of controlled cultivation, standardised analytics, preclinical testing platforms, and collaborative innovation ecosystems and highlight the need for coordinated scientific, technical, and regulatory advances to unlock the full translational potential of marine-derived compounds. Full article

Viral carcinogenesis as a causative mechanism of breast cancer has been intensively researched during the last decades. The role of Epstein–Barr virus (EBV) and Bovine Leukemia virus (BLV) in breast oncogenesis has been investigated in a plethora of studies, but with conflicting results. The aim of this systematic review and meta-analysis was to compare the frequency of molecular detection of the EBV genome and BLV genome between women with breast cancer and women without malignant breast tumors. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to 20 May 2024. Included studies were those comparing the frequency of molecular detection of the EBV and/or BLV genome in breast tissue specimens with polymerase chain reaction (PCR) methods between patients with breast cancer and women without breast malignancies. The primary outcomes of the study were the frequency of molecular detection of the EBV genome and BLV genome. Methodological quality of included studies was assessed using the Newcastle–Ottawa Scale. A total of 29 studies met the selection criteria and were included in this meta-analysis; 19 studies reported results for molecular detection of the EBV genome, 9 studies for detection of the BLV genome and 1 study for detection of genomic material of both viruses. The frequency of molecular detection of viral genomes was significantly higher in patients with breast cancer, compared to women with healthy breasts or benign breast diseases, regarding both EBV (OR: 3.041, 95% CI: 1.791 to 5.164, p < 0.0001) and BLV (OR: 3.459, 95% CI: 2.118 to 5.650, p < 0.0001). The frequency of molecular detection of EBV and BLV genomes is higher, in a statistically significant manner, in patients with breast cancer compared to women without breast malignancies. The presence of these viral factors in breast tissue could imply their potential contribution in breast carcinogenesis, but is not sufficient to establish it, and the molecular detection of their genomes could be potentially exploited in the future for preventive, diagnostic and therapeutic purposes. Further studies are required to thoroughly investigate and establish a causal relationship between EBV and BLV infection and breast carcinogenesis, as well as to support the use of viral genome molecular detection in clinical settings for the management of breast cancer patients. Full article

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

Pediatric sepsis is a life-threatening systemic infectious response syndrome. Its core pathophysiological process involves a systemic imbalance between oxygen delivery and demand, coupled with cellular energy metabolism dysfunction, which collectively contribute to high mortality rates. Parameters of oxygen metabolism serve as critical indicators reflecting tissue perfusion and cellular oxygen utilization. Consequently, these parameters hold significant value for the early identification, severity stratification, therapeutic guidance, and prognostic evaluation of pediatric sepsis. This review systematically elucidates the pathophysiological mechanisms underlying oxygen metabolism disorders in pediatric sepsis. Furthermore, it highlights the current clinical applications and significance of key monitoring indices, including blood lactate, central venous oxygen saturation, oxygen delivery, and oxygen consumption. By integrating recent research advancements, this paper also explores therapeutic strategies aimed at optimizing oxygen metabolism, such as blood purification, microcirculation-targeted therapies, and extracorporeal membrane oxygenation. Finally, we provide future perspectives on emerging biomarkers and metabolomic approaches, aiming to establish a theoretical foundation for the optimized clinical management of pediatric sepsis. Full article

Surgical intervention is a primary treatment for osteosarcoma, often resulting in a tumorous bone defect with an irregular shape. Postoperative management is essential to minimize tumor recurrence risks and promote bone regeneration. To address these issues, we developed a multifunctional injectable, rapidly photo-curable hydrogel composed of gelatin methacryloyl/carboxymethyl chitosan/hyaluronic acid (GelMA/CMCS/HA), modified with vanadium-doped mesoporous bioactive glass (VMBG). The exceptional injectability enables seamless adaptation to irregular bone defects, offering a significant advantage over preformed implants, while the rapid photocurability of the hydrogel ensures stable fixation within minutes, thereby reducing potential risks during surgery. Furthermore, this platform exhibits dual therapeutic efficacy, characterized by antitumor activity and osteogenic induction. In vitro assessments demonstrated that V(V)/V(IV) valence cycling-driven ROS generation mediated its potent antitumor efficacy. Additionally, concurrent enhancement of alkaline phosphatase activity and osteogenic marker expression validated its osteogenic potential. The CMCS incorporation promoted healing at the defect site, while the HA addition created binding sites for cell adhesion and growth, thereby improving scaffold bioactivity. Collectively, this study presents the development and validation of a multifunctional GelMA/CMCS/HA hydrogel, highlighting its dual capability for bone regeneration and tumor suppression within tumor-associated bone microenvironments. Full article

Rationale and objectives: Parkinson’s disease (PD) significantly affects visual function, especially convergence and eye movements, impacting tasks such as reading. The objective was to investigate preliminarily the impact of the use of digital visual training in PD patients with associated convergence insufficiency (CI). Materials and methods: Pre–post pseudo-experimental pilot study to evaluate the impact of a novel digital therapy system (video game for use on a mobile phone or tablet) in 13 patients with PD and CI, with a mean age of 67 years. A comprehensive visual assessment was performed before and after a 6-week home-based visual rehabilitation, including measurement of near point of convergence (NPC), near positive fusional vergence (PFV), oculomotor tests (NSUCO and King-Devick tests), and symptom assessments with two validated questionnaires (CISS and SQVD). Results: Treatment adherence was variable, ranging from 0.8% to 124.7%. Despite this, significant improvements were found after therapy in break (p = 0.022) and recovery points of the NPC (p = 0.007), as well as break (p = 0.003) and recovery points in near PFV (p < 0.001). In the NSUCO test, the total score improved significantly from 23.9 ± 4.2 to 26.2 ± 3.7 after therapy (p = 0.003). Furthermore, a significant reduction in the total King-Devick test time was observed, decreasing from 79.4 ± 28.8 s to 69.0 ± 21.5 s with therapy (p = 0.034). Finally, symptom questionnaire scores also decreased significantly with therapy (CISS p = 0.037, SQVD p < 0.001). Conclusions: The digital vision therapy system evaluated seems to improve oculomotor control and reduce visual symptoms associated with CI in PD patients. Studies with larger sample sizes and a control group are needed to fully validate the therapeutic effectiveness of this tool. Full article

Peripherally restricted (‘second-generation’) cannabinoid CB₁ receptor (CB₁R) antagonists have been suggested to have therapeutic potential in numerous diseases. However, their effects on the cardiovascular system require further research. The peripheral CB₁R antagonist AM6545 failed to modify the decrease in blood pressure (BP) elicited by inhibition of anandamide degradation in spontaneously hypertensive rats. The aims of the present study were to examine the effect of AM6545 on BP and its interaction with endocannabinoid-evoked effects in deoxycorticosterone acetate (DOCA)-salt rats. For this purpose, we applied methanandamide (MethAEA), a stable analogue of anandamide, and URB597, an inhibitor of its degradation, in urethane-anesthetized animals. AM6545 did not affect BP by itself. MethAEA elicited a biphasic effect (a rise in BP, followed by its fall); both phases were antagonized by AM6545. URB597 induced a monophasic hypotensive effect, which was abolished by AM6545 in DOCA-salt rats but further enhanced in control animals. AM6545 also unmasked an additional increase in BP after URB597 in both groups of rats. In conclusion, AM6545 modifies the cardiovascular effects of endocannabinoids in hypertension in a model-dependent manner. The cardiovascular effects of CB₁R antagonists should be carefully evaluated when assessing their potential therapeutic significance, as they may unmask an increase in BP. Full article

Cancer continues to present a profound challenge due to high mortality and the inherent limitations of conventional treatments, including suboptimal targeting, systemic toxicity, and difficulty in overcoming physiological barriers. Micro/nanorobots (MNRs) offer a promising enhanced precision and efficacy in cancer therapy. This review systematically analyzes recent advancements in MNR applications, establishing a consistent framework that interlinks their diverse material compositions, propulsion strategies, and therapeutic functions. We critically compare various materials (inorganic, organic/polymeric, and biological/hybrid materials), elucidating their respective trade-offs in biocompatibility, biodegradability, and stimulus responsiveness. This paper further examines both internal (chemical and biological) and external (magnetic, light, and ultrasound) propulsion mechanisms, highlighting their strengths in overcoming biological barriers and enabling complex in vivo navigation, while also discussing their inherent limitations in control, fuel dependency, and tissue penetration. We then synthesize the therapeutic capabilities of MNRs across targeted drug delivery, phototherapy, radiotherapy, and immunotherapy, emphasizing common advantages like enhanced tumor specificity and reduced systemic side effects. A forward-looking perspective was also provided on the remaining challenges, particularly focusing on in vivo controllability, long-term biosafety, manufacturing scalability, and the significant hurdles in clinical translation. By offering a more critical and integrated analysis, this review underscores the immense potential of MNRs to revolutionize personalized precision cancer treatment, while candidly addressing the complex obstacles that must be surmounted for their successful clinical adoption. Full article

Natural killer (NK) cells are increasingly recognized as a complementary platform to T-cell-based cancer immunotherapies. Their innate, MHC-unrestricted recognition, capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) and comparatively favorable toxicity profile have given rise to a broad therapeutic pipeline that includes cytokine-supported regimens, adoptive NK products, bispecific and trispecific NK engagers, and chimeric antigen receptor (CAR)-engineered NK cells. Clinical data, particularly in hematologic malignancies, show that NK-cell-based strategies can be safe and biologically active, although limited persistence, suboptimal trafficking and immune escape remain key challenges. Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-driven epithelial cancer, illustrates how a tumor microenvironment (TME) can simultaneously impair NK function and create specific vulnerabilities that NK-focused therapies can exploit. This review summarizes NK biology and current therapeutic platforms, analyzes major limitations, highlights the specific context of NK-cell-based strategies in NPC and compares NK- and T-cell-based therapies with an emphasis on clinical translation. Full article

The multidirectional bioactivity of betulin (BN), its widespread occurrence in plants, relatively low toxicity, and acceptable safety profile make it an attractive scaffold for scientific research and potential therapeutic applications. Due to the presence of reactive functional groups (C-3-OH and C-28-OH), BN is an interesting source of new semisynthetic bioactive compounds obtained via structural modifications of the parent backbone. In our study, we designed new BN–amino acid (BNAA) molecular hybrids, aiming to exploit synergistically the properties of both components. We prepared and evaluated a total of 18 new compounds for antitumor activity against the two human cancer cell lines (HCT 116 and MCF-7) and one non-cancerous cell line (NHDF) using a standard Cell Counting Kit-8 (CCK-8) assay. The potential signaling pathways of the obtained BN derivatives were identified based on the measurement of p21 and Bax mRNA expression levels using the RT-qPCR method. We successfully synthesized a series of new BN hybrids by conjugation of the C-3 and C-28 hydroxyl groups via a succinyl (-CO-CH₂-CH₂-CO-, Suc) linker with selected amino acid methyl esters. The structures of all obtained BNAA molecular hybrids were confirmed by spectroscopic analysis (¹H and ¹³C NMR) and high-resolution mass spectrometry (HR-MS). Analysis of the biological activity of the obtained BN derivatives indicated that both the attached amino acids and the substituents at C3 carbon alter BN activity. The obtained BN–amino acid hybrids represent a useful platform for further optimization, especially derivatives (3a, 3e, 3f, and 7d), which showed the most relevant biological profiles in this study. Full article

Intravesical Bacillus Calmette–Guérin (BCG) is a recommended therapy approach for non-muscle invasive bladder cancer (NMIBC) to prevent disease progression and eliminate tumor cells. Nevertheless, some patients have shown resistance to BCG therapy, exhibiting disease recurrence and progression to MIBC, thereby necessitating radical cystectomy as the best-recommended treatment option. However, radical cystectomy greatly affects postoperative morbidity and quality of life, rendering many patients hesitant or surgically unsuitable for this invasive therapy. The concept of bladder preservation has emerged as an alternative, employing a diverse array of therapeutic agents and interventions to improve therapeutic efficacy to retain the bladder for as long as possible. In this review, we explore various established therapeutic agents and ongoing clinical trials involving new potential agents and interventions. This study was undertaken to determine the advantage of each agent and their combined therapeutic regimens in improving prognostic efficacy, offering an alternative to radical cystectomy for BCG-unresponsive NMIBC. Full article

Restless legs syndrome (RLS) is a common sensorimotor disorder with limited treatment options and incompletely understood pathophysiology. Genome-wide association studies have identified numerous risk loci, but translating these findings into causal genes and therapeutic targets remains challenging. We performed a proteome-wide association study (PWAS) integrating RLS genome-wide association study (GWAS) data from FinnGen with two brain pQTL datasets (ROSMAP and Banner). We validated the identified proteins using TWAS, SMR, and colocalization analyses using brain pQTL and eQTL datasets. To further investigate peripheral protein associations, we performed SMR using plasma pQTL data from the UK Biobank Pharma Proteomics Project (UKB-PPP). We also conducted a phenome-wide association study (PheWAS) to screen for potential off-target effects of the prioritized genes, followed by drug prediction using DSigDB and molecular docking. PWAS identified GLO1, along with GRWD1 and MAP2K5, as significantly associated with RLS. GLO1 was identified by brain-based SMR (p = 0.0001), colocalization (PP.H4 = 0.96), TWAS (p = 0.048), and was confirmed by plasma-based SMR (p = 3.16 × 10⁻⁹) as the only protein associated with RLS. PheWAS analysis, without associations for 783 non-RLS phenotypes, confirmed the specificity of GLO1. Among 27 predicted GLO1-targeting compounds, Gambierol had the strongest binding affinity (−8.3 kcal/mol). This proteogenomic study identifies GLO1 as a prioritized causal gene and promising drug target for RLS, combining brain and plasma data to provide new insights into pathogenesis and candidate drug development. Full article