Prolonged survival by combination treatment with a standardized herbal extract from Japanese Kampo-medicine (Juzentaihoto) and gemcitabine in an orthotopic transplantation pancreatic cancer model.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. Traditional Japanese herbal medicine (Kampo), such as Juzentaihoto (a standardized combination of 10 herbal extracts), has shown immune modulatory effects, modulation of microcirculation, and amelioration of fatigue. It is administered to patients to prevent deterioration of cachexia and counteract side effects of chemotherapy.

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease.

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls.

β-Galactosidase- and Photo-Activatable Fluorescent Probes for Protein Labeling and Super-Resolution STED Microscopy in Living Cells.

We report on the synthesis of two fluorescent probes which can be activated by β-Galactosidase (β-Gal) enzymes and/or light. The probes contained 2-nitro-4-oxybenzyl and 3-nitro-4-oxybenzyl fragments, with β-Gal residues linked to C-4. We performed the enzymatic and photoactivation of the probes in a cuvette and compared them, prior to the labeling of fusion protein in live cells with overexpressed β-galactosidase.

Supramolecular Complex of Cucurbit[7]uril with Diketopyrrolopyrole Dye: Fluorescence Boost, Biolabeling and Optical Microscopy.

New photostable and bright supramolecular complexes based on cucurbit[7]uril (CB7) host and diketopyrrolopyrole (DPP) guest dyes having two positively charged 4-(trimethylammonio)phenyl groups were prepared and characterized. The dye core displays large Stokes shift (in HO, abs./emission max.

Cocktail of lipophilic and hydrophilic chemotherapeutics in high-load core@shell nanocarriers to treat pancreatic tumours.

ITC/Toc@Gd(FLP) core@shell nanocarriers with a chemotherapeutic cocktail of lipophilic irinotecan (ITC) as the particle core and hydrophilic fludarabine phosphate (FLP) in the particle shell are realized. They are prepared a microemulsion approach with ITC dissolved in tocopherol (Toc) as droplet phase and stabilized by water-insoluble Gd(FLP). The synthesis can be followed by zeta-potential analysis.

Identification, Organic Synthesis, and Sensitive Analysis of a -Homosalate-Specific Exposure Biomarker.

Homosalate (HMS) is an organic UV filter used in sunscreens and personal care products. Despite its widespread use and detection in environmental matrices, little is known regarding its exposure in humans. HMS is used as a mixture of - and -isomers, and we recently revealed major differences in human toxicokinetics, indicating the need to consider these isomers separately in exposure and risk assessments.

High-Load Gemcitabine Inorganic-Organic Hybrid Nanoparticles as an Image-Guided Tumor-Selective Drug-Delivery System to Treat Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis without effective treatment options. Thus, there is an urgent need for more effective and safe therapies. Here, inorganic-organic hybrid nanoparticles (GMP-IOH-NPs) are presented as a novel drug-delivery system for the selective delivery of extraordinarily high concentrations of gemcitabine monophosphate (GMP), not only to the primary tumor but also to metastatic sites.

Photoactivatable Carbo- and Silicon-Rhodamines and Their Application in MINFLUX Nanoscopy.

New photoactivatable fluorescent dyes (rhodamine, carbo- and silicon-rhodamines [SiR]) with emission ranging from green to far red have been prepared, and their photophysical properties studied. The photocleavable 2-nitrobenzyloxycarbonyl unit with an alpha-carboxyl group as a branching point and additional functionality was attached to a polycyclic and lipophilic fluorescent dye. The photoactivatable probes having the HaloTagTM amine (O2) ligand bound with a dye core were obtained and applied for live-cell staining in stable cell lines incorporating Vimentin (VIM) or Nuclear Pore Complex Protein NUP96 fused with the HaloTag.

Voltage-Gated Potassium Channels Beyond the Action Potential.

Bioelectricity goes far beyond electrical signaling in the nervous system, but this was initially not obvious for me. This article describes the journey from studying the biophysics of ion channels in classical electrically excitable tissues to focusing on the pathogenic roles of the Kv10.1 potassium channel in cancers.

inSPIRE: An Open-Source Tool for Increased Mass Spectrometry Identification Rates Using Prosit Spectral Prediction.

Rescoring of mass spectrometry (MS) search results using spectral predictors can strongly increase peptide spectrum match (PSM) identification rates. This approach is particularly effective when aiming to search MS data against large databases, for example, when dealing with nonspecific cleavage in immunopeptidomics or inflation of the reference database for noncanonical peptide identification. Here, we present inSPIRE (in silico Spectral Predictor Informed REscoring), a flexible and performant open-source rescoring pipeline built on Prosit MS spectral prediction, which is compatible with common database search engines.

iBench: A ground truth approach for advanced validation of mass spectrometry identification method.

The discovery of many noncanonical peptides detectable with sensitive mass spectrometry inside, outside, and on cells shepherded the development of novel methods for their identification, often not supported by a systematic benchmarking with other methods. We here propose iBench, a bioinformatic tool that can construct ground truth proteomics datasets and cognate databases, thereby generating a training court wherein methods, search engines, and proteomics strategies can be tested, and their performances estimated by the same tool. iBench can be coupled to the main database search engines, allows the selection of customized features of mass spectrometry spectra and peptides, provides standard benchmarking outputs, and is open source.

Supramolecular Complex of Photochromic Diarylethene and Cucurbit[7]uril: Fluorescent Photoswitching System for Biolabeling and Imaging.

Photoswitchable fluorophores─proteins and synthetic dyes─whose emission is reversibly switched on and off upon illumination, are powerful probes for bioimaging, protein tracking, and super-resolution microscopy. Compared to proteins, synthetic dyes are smaller and brighter, but their photostability and the number of achievable switching cycles in aqueous solutions are lower. Inspired by the robust photoswitching system of natural proteins, we designed a supramolecular system based on a fluorescent diarylethene () and cucurbit[7]uril (CB7) (denoted as @CB7).

Cleavable Linker Incorporation into a Synthetic Dye-Nanobody-Fluorescent Protein Assembly: FRET, FLIM and STED Microscopy.

A bright and photostable fluorescent dye with a disulfide (S-S) linker and maleimide group (Rho594-S2-mal), as cleavable and reactive sites, was synthesized and conjugated with anti-GFP nanobodies (NB). The binding of EGFP (FRET donor) with anti-GFP NB labeled with one or two Rho594-S2-mal residues was studied in vitro and in cellulo. The linker was cleaved with dithiothreitol recovering the donor (FP) signal.