Mammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 rRNA modifications. Previous works have shown that some rRNA modification types can be dynamically regulated; however, how and when the mammalian rRNA modification landscape is remodeled remains largely unexplored. Here, we employ direct RNA sequencing to chart the human and mouse rRNA epitranscriptome across tissues, developmental stages, cell types, and disease.
View Article and Find Full Text PDFCentral nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood-brain barrier. While protecting the brain's homeostasis, the barrier limits the passage of almost all large-molecule drugs and most small-molecule drugs.
View Article and Find Full Text PDFHair follicles (HFs) represent a route of interest to drug delivery for treating several skin conditions. Iontophoresis, on the other hand, is a physical method to enhance drug permeation by applying a low electrical current to the formulation. HFs can be targeted following topical iontophoretic application, as they represent a pathway of lower electrical resistance, as well as a drug reservoir, in particular useful for nanoparticles (NPs), which can preferably accumulate in these structures.
View Article and Find Full Text PDFThe use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents.
View Article and Find Full Text PDFIntroduction: Molecular profiling of lung cancer is essential to identify genetic alterations that predict response to targeted therapy. While deep learning shows promise for predicting oncogenic mutations from whole tissue images, existing studies often face challenges such as limited sample sizes, a focus on earlier stage patients, and insufficient analysis of robustness and generalizability.
Methods: This retrospective study evaluates factors influencing mutation prediction accuracy using the large Heidelberg Lung Adenocarcinoma Cohort (HLCC), a cohort of 2356 late-stage FFPE samples.
Eur Urol Oncol
August 2024
Background And Objective: Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status.
Methods: A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up.
This study aims to establish and optimize a process for the fabrication of 3D microstructures of the biocompatible polymer Parylene C using hot embossing techniques. The different process parameters such as embossing temperature, embossing force, demolding temperature and speed, and the usage of a release agent were optimized, utilizing adhesive micropillars as a use case. To enhance compatibility with conventional semiconductor fabrication techniques, hot embossing of Parylene C was adapted from conventional stainless steel substrates to silicon chip platforms.
View Article and Find Full Text PDFThe growing importance of submicrometer-structured surfaces across a variety of different fields has driven progress in light manipulation, color diversity, water-repellency, and functional enhancements. To enable mass production, processes like hot-embossing (HE), roll-to-roll replication (R2R), and injection molding (IM) are essential due to their precision and material flexibility. However, these processes are tool-based manufacturing (TBM) techniques requiring metal molds, which are time-consuming and expensive to manufacture, as they mostly rely on galvanoforming using templates made via precision microlithography or two-photon-polymerization (2PP).
View Article and Find Full Text PDFUnderstanding the interplay of the proteome and the metabolome helps to understand cellular regulation and response. To enable robust inferences from such multi-omics analyses, we introduced and evaluated a workflow for combined proteome and metabolome analysis starting from a single sample. Specifically, we integrated established and individually optimized protocols for metabolomic and proteomic profiling (EtOH/MTBE and autoSP3, respectively) into a unified workflow (termed MTBE-SP3), and took advantage of the fact that the protein residue of the metabolomic sample can be used as a direct input for proteome analysis.
View Article and Find Full Text PDFIntroduction: Cystic fibrosis (CF) is associated with pulmonary infections persistent to antibiotics.
Methods: To eradicate biofilms, solid lipid nanoparticles (SLNs) loaded with quorum-sensing-inhibitor (QSI, disrupting bacterial crosstalk), coated with chitosan (CS, improving internalization) and immobilized with alginate lyase (AL, destroying alginate biofilms) were developed.
Results: SLNs (140-205 nm) showed prolonged release of QSI with no sign of acute toxicity to A549 and Calu-3 cells.
Background: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival.
View Article and Find Full Text PDFAddressing the challenge of efficient drug delivery to the lungs, a nano-structured, microparticulate carrier system with defined and customizable dimensions has been developed. Utilizing a template-assisted approach and capillary forces, particles were rapidly loaded and stabilized. The system employs a biocompatible alginate gel as a stabilizing matrix, facilitating the breakdown of the carrier in body fluids with the subsequent release of its nano-load, while also mitigating long-term accumulation in the lung.
View Article and Find Full Text PDFWhile stimuli-responsive structural colors are commonly found in nature, mimicking these in artificial materials is challenging. Dynamically switchable and tunable coloration, however, is in high demand in widespread fields of applications, including advanced display and monitoring technologies, smart sensing, and anticounterfeiting. This work reports a scalable protocol for the synthesis of tailor-made core-shell particles and subsequent processing to opal films with iridescent, pH-responsive, and mechanochromic structural color.
View Article and Find Full Text PDFBackground: Uncomplicated bacterial urinary tract infections(uUTIs) are commonly seen in outpatient practice. They are usuallytreated empirically with antibiotics. The pertinent German ClinicalPractice Guideline contains recommendations on antibiotic selection,with the additional advice that the local resistance situationshould be considered as well.
View Article and Find Full Text PDFPurpose: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting.
View Article and Find Full Text PDFBeilstein J Nanotechnol
November 2023
Nanoparticles have shown an enormous potential as drug delivery systems in the lab. However, translation to the clinics or even market approval often fails. So far, the reason for this discrepancy is manifold.
View Article and Find Full Text PDFBackground: Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression.
Objective: To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease.
Methods: In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS).
Background: Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) database indicates that early diagnosis is significantly associated with favorable outcome.
View Article and Find Full Text PDFHuman respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles.
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