Title: Metabolism and cytotoxicity studies of the two hallucinogens 1cP-LSD and 4-AcO-DET in human liver and zebrafish larvae models using LC-HRMS/MS and a high-content screening assay.

Authors: Gampfer TM and Schütz V and Schippers P and Rasheed S and Baumann J and Wagmann L and Pulver B and Westphal F and Flockerzi V and Müller R and Meyer MR

Journal: Journal of pharmaceutical and biomedical analysis

Date: 2024 Aug 01

DOI: 10.1016/j.jpba.2024.116187

Abstract: The continuous emergence of new psychoactive substances (NPS) attracted a great deal of attention within recent years. Lately, the two hallucinogenic NPS 1cP-LSD and 4-AcO-DET have appeared on the global market. Knowledge about their metabolism to identify potential metabolic targets for analysis and their cytotoxic properties is lacking. The aim of this work was thus to study their in vitro and in vivo metabolism in pooled human liver S9 fraction (pHLS9) and in zebrafish larvae (ZL) by means of liquid chromatography-high-resolution tandem mass spectrometry. Monooxygenases involved in the initial metabolic steps were elucidated using recombinant human isozymes. Investigations on their cytotoxicity were performed on the human hepatoma cell line HepG2 using a multiparametric, fluorescence-based high-content screening assay. This included measurement of CYP-enzyme mediated effects by means of the unspecific CYP inhibitor 1-aminbenzotriazole (ABT). Several phase I metabolites of both compounds and two phase II metabolites of 4-AcO-DET were produced in vitro and in vivo. After microinjection of 1cP-LSD into the caudal vein of ZL, three out of seven metabolites formed in pHLS9 were also detected in ZL. Twelve 4-AcO-DET metabolites were identified in ZL after exposure via immersion bath and five of them were found in pHLS9 incubations. Notably, unique metabolites of 4-AcO-DET were only produced by ZL, whereas 1cP-LSD specific metabolites were found both in ZL and in pHLS9. No toxic effects were observed for 1cP-LSD and 4-AcO-DET in HepG2 cells, however, two parameters were altered in incubations containing 4-AcO-DET together with ABT compared with incubations without ABT but in concentrations far above expected in vivo concentration. Further investigations should be done with other hepatic cell lines expressing higher levels of CYP enzymes.

Title: SingmiR: a single-cell miRNA alignment and analysis tool.

Authors: Engel A and Rishik S and Hirsch P and Keller V and Fehlmann T and Kern F and Keller A

Journal: Nucleic acids research

Date: 2024 Jul 05

DOI: 10.1093/nar/gkae225

Abstract: Single-cell RNA sequencing (RNA-seq) has revolutionized our understanding of cell biology, developmental and pathophysiological molecular processes, paving the way toward novel diagnostic and therapeutic approaches. However, most of the gene regulatory processes on the single-cell level are still unknown, including post-transcriptional control conferred by microRNAs (miRNAs). Like the established single-cell gene expression analysis, advanced computational expertise is required to comprehensively process newly emerging single-cell miRNA-seq datasets. A web server providing a workflow tailored for single-cell miRNA-seq data with a self-explanatory interface is currently not available. Here, we present SingmiR, enabling the rapid (pre-)processing and quantification of human miRNAs from noncoding single-cell samples. It performs read trimming for different library preparation protocols, generates automated quality control reports and provides feature-normalized count files. Numerous standard and advanced analyses such as dimension reduction, clustered feature heatmaps, sample correlation heatmaps and differential expression statistics are implemented. We aim to speed up the prototyping pipeline for biologists developing single-cell miRNA-seq protocols on small to medium-sized datasets. SingmiR is freely available to all users without the need for a login at https://www.ccb.uni-saarland.de/singmir.

Title: A Novel 3D Printed Model of Infected Human Hair Follicles to Demonstrate Targeted Delivery of Nanoantibiotics.

Authors: Aliyazdi S and Frisch S and Neu T and Veldung B and Karande P and Schaefer UF and Loretz B and Vogt T and Lehr CM

Journal: ACS biomaterials science & engineering

Date: 2024 Jul 03

DOI: 10.1021/acsbiomaterials.4c00570

Abstract: Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle\'s microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment\'s critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.

Title: Synthesis and biological evaluation of moiramide B derivatives.

Authors: Andler O and Kazmaier U

Journal: Organic & biomolecular chemistry

Date: 2024 Jul 03

DOI: 10.1039/d4ob00856a

Abstract: Moiramide B is a peptide-polyketide hybrid with a bacterial origin and interesting antibiotic activity. Besides its structurally conserved peptide part, it contains a highly variable fatty acid side chain. We modified this part of the molecule by introducing a terminal alkyne, and we then subjected it to click reactions and Sonogashira couplings. This provided a library of moiramide B derivatives with high and selective in vivo activities against S. aureus.

Title: Pd(8)(PDip)(6): Cubic, Unsaturated, Zerovalent.

Authors: Breitwieser K and Bevilacqua M and Mullassery S and Dankert F and Morgenstern B and Grandthyll S and Müller F and Biffis A and Hering-Junghans C and Munz D

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Date: 2024 Jul

DOI: 10.1002/advs.202400699

Abstract: Atomically precise nanoclusters hold promise for supramolecular assembly and (opto)electronic- as well as magnetic materials. Herein, this work reports that treating palladium(0) precursors with a triphosphirane affords strongly colored Pd₈(PDip)₆ that is fully characterized by mass spectrometry, heteronuclear and Cross-Polarization Magic-Angle Spinning (CP-MAS) NMR-, infrared (IR), UV-vis, and X-ray photoelectron (XP) spectroscopies, single-crystal X-Ray diffraction (sc-XRD), mass spectrometry, and cyclovoltammetry (CV). This coordinatively unsaturated 104-electron Pd(0) cluster features a cubic Pd₈-core, µ₄-capping phosphinidene ligands, and is air-stable. Quantum chemical calculations provide insight to the cluster\'s electronic structure and suggest 5s/4d orbital mixing as well as minor Pd─P covalency. Trapping experiments reveal that cluster growth proceeds via insertion of Pd(0) into the triphosphirane. The unsaturated cluster senses ethylene and binds isocyanides, which triggers the rearrangement to a tetrahedral structure with a reduced frontier orbital energy gap. These experiments demonstrate facile cluster manipulation and highlight non-destructive cluster rearrangement as is required for supramolecular assembly.

Title: Thermotropic liquid crystals in drug delivery: A versatile carrier for controlled release.

Authors: Nesterkina M and Kravchenko I and Hirsch AKH and Lehr CM

Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Date: 2024 Jul

DOI: 10.1016/j.ejpb.2024.114343

Abstract: Responsive and adaptive soft-matter systems represent an advanced category of materials with potential applications in drug delivery. Among these, liquid crystals (LCs) emerge as multifunctional anisotropic scaffolds capable of reacting to temperature, light, electric or magnetic fields. Specifically, the ordering and physical characteristics of thermotropic LCs are primarily contingent on temperature as an external stimulus. This comprehensive review aims to bridge a notable gap in the biomedical application of thermotropic mesogens by exclusively focusing on drug delivery. Anticipated to inspire diverse ideas, the review intends to facilitate the elegant exploitation of controllable and temperature-induced characteristics of LCs to enhance drug permeation. Here, we delineate recent advancements in thermally-driven LCs with a substantial emphasis on LC monomer mixtures, elastomers, polymers, microcapsules and membranes. Moreover, special emphasis is placed on the biocompatibility and toxicity of LCs as the foremost prerequisite for their application in healthcare. Given the promising prospect of thermotropic LC formulations in a clinical context, a special section is devoted to skin drug delivery. The review covers content from multiple disciplines, primarily targeting researchers interested in innovative strategies in drug delivery. It also appeals to those enthusiastic about firsthand exploration of the feasible biomedical applications of thermotropic LCs. To the best of our knowledge, this marks the first review addressing thermotropic LCs as tunable soft-matter systems for drug delivery.

Title: Self-Lubricating, Living Contact Lenses.

Authors: Puertas-Bartolomé M and Gutiérrez-Urrutia I and Teruel-Enrico LL and Duong CN and Desai K and Trujillo S and Wittmann C and Del Campo A

Journal: Advanced materials (Deerfield Beach, Fla.)

Date: 2024 Jul

DOI: 10.1002/adma.202313848

Abstract: The increasing prevalence of dry eye syndrome in aging and digital societies compromises long-term contact lens (CL) wear and forces users to regular eye drop instillation to alleviate discomfort. Here a novel approach with the potential to improve and extend the lubrication properties of CLs is presented. This is achieved by embedding lubricant-secreting biofactories within the CL material. The self-replenishable reservoirs autonomously produce and release hyaluronic acid (HA), a natural lubrication and wetting agent, long term. The hydrogel matrix regulates the growth of the biofactories and the HA production, and allows the diffusion of nutrients and HA for at least 3 weeks. The continuous release of HA sustainably reduces the friction coefficient of the CL surface. A self-lubricating CL prototype is presented, where the functional biofactories are contained in a functional ring at the lens periphery, outside of the vision area. The device is cytocompatible and fulfils physicochemical requirements of commercial CLs. The fabrication process is compatible with current manufacturing processes of CLs for vision correction. It is envisioned that the durable-by-design approach in living CL could enable long-term wear comfort for CL users and minimize the need for lubricating eye drops.

Title: Addressing female underrepresentation in sport & exercise-related research: JSAMS policy for submitted studies (& subsequent considerations).

Authors: Meyer T and Cobley S

Journal: Journal of science and medicine in sport

Date: 2024 Jul

DOI: 10.1016/j.jsams.2024.05.018

Abstract: on="1.0" ?>\n \n \n 38879218 2024 06 15 2024 06 15

Title: Thermotropic liquid crystals in drug delivery: A versatile carrier for controlled release.

Authors: Nesterkina M and Kravchenko I and Hirsch AKH and Lehr CM

Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Date: 2024 Jul

DOI: 10.1016/j.ejpb.2024.114343

Abstract: Responsive and adaptive soft-matter systems represent an advanced category of materials with potential applications in drug delivery. Among these, liquid crystals (LCs) emerge as multifunctional anisotropic scaffolds capable of reacting to temperature, light, electric or magnetic fields. Specifically, the ordering and physical characteristics of thermotropic LCs are primarily contingent on temperature as an external stimulus. This comprehensive review aims to bridge a notable gap in the biomedical application of thermotropic mesogens by exclusively focusing on drug delivery. Anticipated to inspire diverse ideas, the review intends to facilitate the elegant exploitation of controllable and temperature-induced characteristics of LCs to enhance drug permeation. Here, we delineate recent advancements in thermally-driven LCs with a substantial emphasis on LC monomer mixtures, elastomers, polymers, microcapsules and membranes. Moreover, special emphasis is placed on the biocompatibility and toxicity of LCs as the foremost prerequisite for their application in healthcare. Given the promising prospect of thermotropic LC formulations in a clinical context, a special section is devoted to skin drug delivery. The review covers content from multiple disciplines, primarily targeting researchers interested in innovative strategies in drug delivery. It also appeals to those enthusiastic about firsthand exploration of the feasible biomedical applications of thermotropic LCs. To the best of our knowledge, this marks the first review addressing thermotropic LCs as tunable soft-matter systems for drug delivery.

Title: Arg-biodynamers as antibiotic potentiators through interacting with Gram-negative outer membrane lipopolysaccharides.

Authors: Kamal MAM and Bassil J and Loretz B and Hirsch AKH and Lee S and Lehr CM

Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Date: 2024 Jul

DOI: 10.1016/j.ejpb.2024.114336

Abstract: Antimicrobial resistance is becoming more prominent day after day due to a number of mechanisms by microbes, especially the sophisticated biological barriers of bacteria, especially in Gram-negatives. There, the lipopolysaccharides (LPS) layer is a unique component of the outer leaflet of the outer membrane which is highly impermeable and prevents antibiotics from passing passively into the intracellular compartments. Biodynamers, a novel class of dynamically bio-responsive polymers, may open new perspectives to overcome this particular barrier by accommodating various secondary structures and form supramolecular structures in such bacterial microenvironments. Generally, bio-responsive polymers are not only candidates as bio-active molecules against bacteria but also carriers via their interactions with the cargo. Based on their dynamicity, design flexibility, biodegradability, biocompatibility, and pH-responsiveness, we investigated the potential of two peptide-based biodynamers for improving antimicrobial drug delivery. By a range of experimental methods, we discovered a greater affinity of Arg-biodynamers for bacterial membranes than for mammalian membranes as well as an enhanced LPS targeting on the bacterial membrane, opening perspectives for enhancing the delivery of antimicrobials across the Gram-negative bacterial cell envelope. This could be explained by the change of the secondary structure of Arg-biodynamers into a predominant β-sheet character in the LPS microenvironment, by contrast to the α-helical structure typically observed for most lipid membrane-permeabilizing peptides. In comparison to poly-L-arginine, the intrinsic antibacterial activity of Arg-biodynamers was nearly unchanged, but its toxicity against mammalian cells was >128-fold reduced. When used in bacterio as an antibiotic potentiator, however, Arg-biodynamers improved the minimum inhibitory concentration (MIC) against Escherichia coli by 32 times compared to colistin alone. Similar effect has also been observed in two stains of Pseudomonas aeruginosa. Arg-biodynamers may therefore represent an interesting option as an adjuvant for antibiotics against Gram-negative bacteria and to overcome antimicrobial resistance.

Title: Design and evaluation of nanostructured lipid carrier of Bergenin isolated from Pentaclethra macrophylla for anti-inflammatory effect on lipopolysaccharide-induced inflammatory responses in macrophages.

Authors: Nnamani PO and Nwagwu C and Diovu EO and Abonyi OE and Nesterkina M and Neu T and Richter C and Loretz B and Lehr CM

Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Date: 2024 Jul

DOI: 10.1016/j.ejpb.2024.114307

Abstract: Herein, we report the properties of nanostructured lipid carriers (NLCs) prepared with a gradient concentration of Bergenin (BGN) isolated from Pentaclethra macrophylla stem bark powder. A gradient concentration of BGN (BGN 0, 50, 100, 150, and 200 mg) was prepared in a 5 % lipid matrix consisting of Transcutol HP (75 %), Phospholipon 90H (15 %), and Gelucire 43/01 (10 %) to which a surfactant aqueous phase consisting of Tween 80, sorbitol, and sorbic acid was dissolved. The NLCs were evaluated by size, polydispersity index (PDI), zeta potential, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), encapsulation efficiency, and in vitro drug release. The result shows polydispersed nanoparticles with high drug encapsulation (94.26-99.50 %). The nanoparticles were mostly spherical, but those from the 50 mg BGN batch were more cuboidal than spherical. The drug release was highest from the latter to the tune of 40 % compared to the pure BGN solution, which released about 15 % BGN. The anti-inflammatory activity of the BGN-NLC and total plant extract was studied on lipopolysaccharide (LPS)-inflamed macrophages. The cell study showed that BGN and plant extract had low cytotoxicity on macrophages and exhibited a dose-dependent anti-inflammatory effect on the LPS-induced inflammatory process in macrophages.

Title: Steatotische Lebererkrankung mit metabolischer Funktionsstörung – die neue Nomenklatur zur Fettleber im deutschen Kontext.

Authors: Schattenberg JM and Tacke F

Journal: Zeitschrift fur Gastroenterologie

Date: 2024 Jul

DOI: 10.1055/a-2287-6138

Abstract: on="1.0" ?>\n \n \n 38976983 2024 07 08 2024 07 08

Title: Letter: Breaking new ground-Understanding the role of ATI-free diet in managing MASLD-Authors' reply.

Authors: Armandi A and Schuppan D and Schattenberg JM

Journal: Alimentary pharmacology & therapeutics

Date: 2024 Jul

DOI: 10.1111/apt.18119

Abstract: on="1.0" ?>\n \n \n 38860612 2024 06 27 2024 06 27

Title: Clinical guideline highlights for the hospitalist: Management of COVID-19.

Authors: Thomas S and Clark D

Journal: Journal of hospital medicine

Date: 2024 Jun 30

DOI: 10.1002/jhm.13437

Abstract: 2023 IDSA Guidelines on the Treatment and Management of Patients with COVID-19 RELEASE DATE: 06/26/2023 PRIOR VERSION (S): 2021 DEVELOPER: Infectious Diseases Society of America FUNDING SOURCE: Infectious Diseases Society of America TARGET POPULATION: Patients with COVID-19 Infection.

Title: Preconditioning Strategies for Improving the Outcome of Fat Grafting.

Authors: Bonomi F and Limido E and Weinzierl A and Harder Y and Menger MD and Laschke MW

Journal: Tissue engineering. Part B, Reviews

Date: 2024 Jun 27

DOI: 10.1089/ten.TEB.2024.0090

Abstract: Autologous fat grafting is a common procedure in plastic, reconstructive, and aesthetic surgery. However, it is frequently associated with an unpredictable resorption rate of the graft depending on the engraftment kinetics. This, in turn, is determined by the interaction of the grafted adipose tissue with the tissue at the recipient site. Accordingly, preconditioning strategies have been developed following the principle of exposing these tissues in the pretransplantation phase to stimuli inducing endogenous protective and regenerative cellular adaptations, such as the upregulation of stress-response genes or the release of cytokines and growth factors. As summarized in the present review, these stimuli include hypoxia, dietary restriction, local mechanical stress, heat, and exposure to fractional carbon dioxide laser. Preclinical studies show that they promote cell viability, adipogenesis, and angiogenesis, while reducing inflammation, fibrosis, and cyst formation, resulting in a higher survival rate and quality of fat grafts in different experimental settings. Hence, preconditioning represents a promising approach to improve the outcome of fat grafting in future clinical practice. For this purpose, it is necessary to establish standardized preconditioning protocols for specific clinical applications that are efficient, safe, and easy to implement into routine procedures.