About
Welcome to PharmaScienceHub
The PharmaScienceHub (PSH) is a collaboration platform of the University of Saarland and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), which has emerged from a close collaboration of the partners over the last 15 years. Its goal is the rapid and efficient identification and development of pharmaceuticals against societally relevant diseases such as infections, cancer and age-related diseases. In the PSH, more than 70 research groups and over 300 researchers from various disciplines work closely together. They benefit from collaboration with 20 regional and interregional companies as well as a close partnership with actors from the pharmaceutical and biotech industry at a national and international level. The PSH also actively promotes start-ups: to date, more than 10 successful spin-offs have emerged from the long-term partnership.
Objectives
- Accelerate Drug Development: Transform promising research results into market-ready medicines swiftly and efficiently.
- Enhance Interdisciplinary Collaboration: Integrate efforts in biomedical-pharmaceutical drug discovery, clinical medicine, and (bio)informatics.
- Foster Industry Partnerships: Collaborate closely with national and international partners from the pharmaceutical and biotech industries.
- Translational Drug Research & Start-Ups: Enable efficient transition of innovative developments from basic research to clinical application. Encourage the creation of start-ups.
- Infrastructure: joint use of extensive laboratory space and state-of-the-art research equipment. Our laboratories will be significantly expanded in the coming years to make the location even more attractive for the development. of drugs
Members and External Local Collaborators
Alexander Titz
Alexander aims at the development of antibacterial drugs using a combination of medicinal chemistry, biochemistry and microbiological methods.
Alexandra K. Kiemer
Alexandra investigates molecular signalling pathways with a focus on inflammatory processes and their link to metabolic pathologies.
Alexey Gurevich
Alexey's research group focuses on bioinformatics to analyze and interpret human-microbe interactions for health and disease insights.
Andrea Volkamer
Andrea develops methods at the interface between structural bioinformatics and cheminformatics, mostly applied in the context of computer-aided drug design with a focus on machine learning methods.
Andreas Keller
Andreas’ research focuses on computational methods for the analysis of nucleic acids, primarily RNAs.
Andriy Luzhetskyy
Andriy aims to develop a synthetic biology platform for discovering, bioengineering, and sustainably producing hidden genomic compounds for pharmacological testing.
Anna KH Hirsch
Anna's research primarily revolves around antibiotic drug discovery and natural product biosynthesis.
Aránzazu del Campo
Maria is associated with the Leibniz Institute for New Materials (INM), specializing in bioinspired, adaptive materials.
Bruno Scheller
Bruno leads a globally renowned research group in preclinical and clinical studies on local drug delivery and new catheter-based interventional therapies.
Chantal Bader
Chantal studies rare soil bacteria to discover new antiparasitic and antiinfective metabolites using microbiology and multi-omics methods like mass spectrometry.
Chengzhang Fu
Chengzhang conducts research at HIPS on chemical biology and bioactive natural products.
Christian Ducho
Christian's research centers around organic and bioorganic chemistry, with a particular focus on nucleic acids and peptides.
Christine Beemelmanns
Christine explores the potential of microbiota-derived substances to develop anti-infective therapies.
Christoph Wittmann
Christoph researches the systems biology of microorganisms to develop tailored cell factories for bioproduction and explore new therapeutic options.
Claus Jacob
Claus focuses on developing selective drug molecules, particularly redox-active agents, while also exploring the philosophy of pharmacy, including epistemology, ethics, and the communication of science.
Claus-Michael Lehr
Claus-Michael's research interests include drug delivery systems and understanding biological barriers for drug transport.
Daniela Yildiz
Daniela's research in pharmacology and toxicology focuses on receptor pharmacology and cellular signaling.
Dietrich Klakow
Dietrich studies complex biological systems, employing computational and experimental approaches to understand underlying mechanisms.
Dominik Munz
Dominik focuses on inorganic chemistry, energy conversion, and organic materials, studying reaction mechanisms, bond activation, and spectroscopy.
Dora Tang
Dora’s research combines synthetic biology, biophysics, and physical chemistry to build minimal synthetic cells, exploring questions of life’s origin and focusing on non-equilibrium behaviors.
Fabian Kern
Fabian develops bioinformatics methods to support infection research and anti-infective development using spatially and temporally resolved single-cell RNA sequencing.
Fabian Müller
Fabian studies statistical modeling of cell regulatory patterns to create interpretable models that reveal molecular relationships and can be experimentally tested.
Florian Hubrich
Florian investigates Natural Products from underexplored pathways and extreme environments.
Franziska Lautenschläger
Franziska studies the role of the cytoskeleton in cell migration, polarity, and mechanics to enhance understanding of cellular mechanisms and processes.
Gabriella Krasteva-Christ
Gabriella studies the molecular steps that turn pathogen detection into inflammation, focusing on the interaction between airway cells and the autonomic nervous system.
Isabel Valera
Isabel works on cutting-edge trustworthy machine learning methods with fair, interpretable and robust behaviour.
Jilles Vreeken
Jilles conducts research in data mining and knowledge discovery, focusing on developing algorithms that can extract meaningful patterns from data.
Jochen S. Hub
Jochen’s creates methods for molecular simulations to understand the structure, dynamics, and function of biological molecules.
Jörn M. Schattenberg
Jörn’s develops new diagnostic and therapeutic approaches for liver diseases, including innovative concepts for early detection, prevention, and treatment of metabolic liver diseases.
Julia Schulze-Hentrich
Julias research focuses on the analysis of gene expression and epigenetic modifications in health and disease.
Kenan Bozhüyük
Kenan is a researcher at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) focusing on microbial natural products and their potential for developing new antibiotics.
Krikamol Muandet
Krikamol’s research focuses on machine learning, including statistical learning theory, kernel methods, causal inference, and algorithmic game theory.
Kristina Scherbaum
Kristina is the Managing Director of the PharmaScienceHub overseeing its administration, outreach activities and financial affairs.
Laura Aradilla Zapata
Laura studies how individual cytoskeletal components work together in cell functions, using biophysics, biochemistry, and molecular biology to analyze these systems from molecular to cellular scales.
Lorenz Thurner
Lorenz’ research focuses on autoimmune diseases, studying how progranulin and B cell receptors contribute to inflammation and lymphoma, with a focus on diagnosis and treatment.
Marc Remke
Marc specializes in pediatric oncology, studying molecular mechanisms of brain tumors and developing targeted therapies.
Marc Schneider
Marc’s research focuses on micro- and nanoparticle drug carriers, nanotechnology in pharmacy, and pulmonary and transdermal drug delivery using advanced microscopy techniques.
Mariia Nesterkina
Maria’s research focuses on bioorganic/medicinal chemistry and drug delivery, particularly developing thermotropic liquid crystal systems for temperature-sensitive skin drug delivery.
Mario Fritz
Mario Fritz's research group works on Trustworthy Information Processing with a focus on the intersection of AI & Machine Learning with Security & Privacy.
Markus Hecht
Markus’ research focuses on radiation oncology, particularly in developing personalized cancer treatment strategies.
Markus Hoth
Markus focuses on biophysics, particularly in understanding the physical principles of biological systems.
Markus R. Meyer
Markus's research includes analytical toxicology and the pharmacokinetics of psychoactive substances.
Martin Empting
Martin is a researcher at HIPS focusing on the design and synthesis of anti-infective agents, targeting bacterial virulence factors.
Martina Sester
Martina's research primarily revolves around transplant immunology and infectious diseases.
Matthias Hannig
Matthias’ research delves into dental materials and their interactions with oral tissues, focusing on biomaterials for restorative dentistry and dental implantology.
Matthias W. Laschke
Matthias conducts research and provides experimental surgical training and services.
Michael Backes
Michael Backes is the founding director of CISPA and conducts research in computer security and privacy.
Olga Kalinina
Olga's research focuses on computational methods in drug discovery, particularly in the field of bioinformatics.
Oskar Staufer
Oskar develops synthetic cell technologies and novel biomaterials to tackle pressing problems in immunology and immunotherapy
Rebekka Burkholz
Rebekka is focusing on understanding deep learning through a complex network perspective to improve algorithms.
Robert Bals
Robert specializes in respiratory medicine, particularly in chronic obstructive pulmonary disease (COPD) and cystic fibrosis research.
Robert Ernst
Robert uses interdisciplinary methods like genetics, biochemistry, and biophysics to study membrane sensors and their role in cell fate, focusing on protein folding and lipid metabolism.
Roland Rolles
Roland is the Vice-President for Administration and Finance at Saarland University, overseeing Central Administration and managing the university’s financial affairs.
Rolf Müller
Rolf's research is centered on the discovery and development of microbial natural products with pharmaceutical potential.
Sandra Iden
Sandra's research focuses on cell biology and cancer, particularly in understanding cell migration and metastasis.
Sangeun Lee
Sangeun Lee’s research focuses on pharmaceutical technology and drug delivery systems.
Sara Trujillo-Munoz
Sara works on biomedical engineering and materials science, particularly in developing materials for tissue engineering.
Sigrun Smola
Sigrun's research focuses on virology, particularly on human papillomaviruses and their role in cancer.
Sören L. Becker
Sören's research focuses on medical microbiology and hygiene, offering diagnostic and research services in infectious diseases.
Stefan Rupf
Stefan works in Synoptic Dentistry at the Clinic for Restorative Dentistry, Periodontology, and Preventive Dentistry.
Stephanie Thomas
Stephanie is the Administrative Director of HIPS, overseeing non-scientific processes and coordinating administration between HIPS in Saarbrücken and HZI in Braunschweig.
Sven Rahmann
Sven's research spans bioinformatics and computational biology, particularly in genomics and transcriptomics.
Tanja Gulder
Tanja's research focuses on organic chemistry, particularly in the synthesis of complex natural products.
Thorsten Lehr
Thorsten's research spans the fields of pharmacology and toxicology, particularly in drug metabolism and drug transport.
Tim Meyer
Tim’s research focuses on sports medicine, exercise physiology, football-related health, exercise-induced fatigue, recovery, preventive training, and using sport as therapy for chronic diseases.
Tobias Gulder
Tobias specializes in the field of bioorganic chemistry, investigating enzyme mechanisms and biosynthetic pathways.
Tobias Hartmann
Tobias work focuses on experimental neurology including clinical treatments, integrating various neuroscience disciplines.
Uli Kazmaier
Ulli conducts research in organic chemistry with a focus on catalysis and synthetic methodology.
Ulrich Boehm
Ulrich's research encompasses pharmacology and toxicology, with a focus on receptor pharmacology.
Vahid Babei
Vahid's research interest lies at the intersection of design, manufacturing and artificial intelligence. His research goal is to develop data-driven algorithms for both engineering design and advanced manufacturing.
Verena Wolf
Verena develops computational methods for simulating and analyzing complex biological and technical systems, focusing on stochastic modeling, efficient simulation, parameter estimation, and reinforcement learning.
Volkhard Helms
Volkhard develops simulation methods and software to study the dynamics, energetics, and interactions of protein-ligand and multi-protein systems.
Walid Elgaher
Walid’s work focuses on the application of various drug design approaches and the use of biophysical and computational techniques for drug discovery and optimization, especially in the field of antimicrobial research.
Wilfried Weber
Wilfried engineer nature’s molecular sensing and response systems to precisely control the functions of cells and materials.
Research Areas
Members
- Hover a data point to display corresponding members.
Recent Publications
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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. - Gampfer TM et al.
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.
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SingmiR: a single-cell miRNA alignment and analysis tool. - Engel A et al.
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.
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A Novel 3D Printed Model of Infected Human Hair Follicles to Demonstrate Targeted Delivery of Nanoantibiotics. - Aliyazdi S et al.
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.
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Synthesis and biological evaluation of moiramide B derivatives. - Andler O et al.
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.
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Pd(8)(PDip)(6): Cubic, Unsaturated, Zerovalent. - Breitwieser K et al.
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
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.
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Thermotropic liquid crystals in drug delivery: A versatile carrier for controlled release. - Nesterkina M et al.
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.
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Self-Lubricating, Living Contact Lenses. - Puertas-Bartolomé M et al.
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
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.
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Addressing female underrepresentation in sport & exercise-related research: JSAMS policy for submitted studies (& subsequent considerations). - Meyer T et al.
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 1878-1861 27 7 2024 Jul Journal of science and medicine in sport J Sci Med Sport Addressing female underrepresentation in sport & exercise-related research: JSAMS policy for submitted studies (& subsequent considerations). 435 436 435-436 10.1016/j.jsams.2024.05.018 S1440-2440(24)00211-1 Meyer Tim T Cobley Stephen S eng Editorial Australia J Sci Med Sport 9812598 1878-1861 IM Humans Female Editorial Policies Exercise Sports Sports Medicine Sexism Periodicals as Topic 2024 6 16 11 59 2024 6 16 11 58 2024 6 15 20 57 ppublish 38879218 10.1016/j.jsams.2024.05.018 S1440-2440(24)00211-1 -
Thermotropic liquid crystals in drug delivery: A versatile carrier for controlled release. - Nesterkina M et al.
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.
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Arg-biodynamers as antibiotic potentiators through interacting with Gram-negative outer membrane lipopolysaccharides. - Kamal MAM et al.
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.
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Design and evaluation of nanostructured lipid carrier of Bergenin isolated from Pentaclethra macrophylla for anti-inflammatory effect on lipopolysaccharide-induced inflammatory responses in macrophages. - Nnamani PO et al.
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.
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Steatotische Lebererkrankung mit metabolischer Funktionsstörung – die neue Nomenklatur zur Fettleber im deutschen Kontext. - Schattenberg JM et al.
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 1439-7803 62 7 2024 Jul Zeitschrift fur Gastroenterologie Z Gastroenterol [Not Available]. 1074 1076 1074-1076 10.1055/a-2287-6138 Schattenberg Jörn M JM 0000-0002-4224-4703 Klinik für Innere Medizin II des Universitätsklinikums des Saarlandes, Homburg, Deutschland. Tacke Frank F 0000-0001-6206-0226 Charité Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Deutschland. ger Journal Article Steatotische Lebererkrankung mit metabolischer Funktionsstörung – die neue Nomenklatur zur Fettleber im deutschen Kontext. 2024 07 08 Germany Z Gastroenterol 0033370 0044-2771 IM Humans Germany Terminology as Topic Fatty Liver classification JMS Consultant: Alentis Therapeutics, Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, Gilead Sciences, GSK, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers. Research Funding: Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH. Stock Options: AGED diagnostics, Hepta Bio. Speaker Honorarium: Advanz, Echosens, MedPublico GmbH. 2024 7 9 0 43 2024 7 9 0 42 2024 7 8 18 43 ppublish 38976983 10.1055/a-2287-6138 -
Letter: Breaking new ground-Understanding the role of ATI-free diet in managing MASLD-Authors' reply. - Armandi A et al.
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 1365-2036 60 2 2024 Jul Alimentary pharmacology & therapeutics Aliment Pharmacol Ther Letter: Breaking new ground-Understanding the role of ATI-free diet in managing MASLD-Authors\' reply. 304 305 304-305 10.1111/apt.18119 Armandi Angelo A 0000-0002-7245-4445 Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy. Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Schuppan Detlef D 0000-0002-4972-1293 University Medical Center, Institute of Translational Immunology and Research Center for Immunotherapy, Johannes Gutenberg-University, Mainz, Germany. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Schattenberg Jörn M JM Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany. eng Letter 2024 06 11 England Aliment Pharmacol Ther 8707234 0269-2813 IM 2024 6 27 6 42 2024 6 11 12 43 2024 6 11 7 33 ppublish 38860612 10.1111/apt.18119 REFERENCES Spertino M, Rossi RE, Pugliese N. Letter: Breaking new ground—understanding the role of ATI‐free diet in managing MASLD. Aliment Pharmacol Ther. 2024;60:302–303. Armandi A, Bespaljko H, Mang A, Huber Y, Michel M, Labenz C, et al. Short‐term reduction of dietary gluten improves metabolic‐dysfunction associated steatotic liver disease: a randomised, controlled proof‐of‐concept study. Aliment Pharmacol Ther. 2024;59:1212–1222. https://doi.org/10.1111/apt.17941 Michel M, Doll M, Albert N, Morgenstern M, Behr A, Maxeiner S, et al. Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes. United European Gastroenterol J. 2024;12(1):11–21. https://doi.org/10.1002/ueg2.12511 Tilg H, Adolph TE, Trauner M. Gut‐liver axis: pathophysiological concepts and clinical implications. Cell Metab. 2022;34(11):1700–1718. https://doi.org/10.1016/j.cmet.2022.09.017 Ashfaq‐Khan M, Aslam M, Qureshi MA, Senkowski MS, Yen‐Weng S, Strand S, et al. Dietary wheat amylase trypsin inhibitors promote features of murine non‐alcoholic fatty liver disease. Sci Rep. 2019;9:17463. https://doi.org/10.1038/s41598‐019‐53323‐x Tortora R, Capone P, De Stefano G, Imperatore N, Gerbino N, Donetto S, et al. Metabolic syndrome in patients with coeliac disease on a gluten‐free diet. Aliment Pharmacol Ther. 2015;41(4):352–359. https://doi.org/10.1111/apt.13062 Romero‐Gómez M, Zelber‐Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829–846. https://doi.org/10.1016/j.jhep.2017.05.016 Liwinski T, Hübener S, Henze L, Hübener P, Heinemann M, Tetzlaff M, et al. A prospective pilot study of a gluten‐free diet for primary sclerosing cholangitis and associated colitis. Aliment Pharmacol Ther. 2023;57:224–236. https://doi.org/10.1111/apt.17256 Engel S, Klotz L, Wirth T, Fleck AK, Pickert G, Eschborn M, et al. Attenuation of immune activation in patients with multiple sclerosis on a wheat‐reduced diet: a pilot crossover trial. Ther Adv Neurol Disord. 2023;25(16):1–12. https://doi.org/10.1177/17562864231170928 -
Clinical guideline highlights for the hospitalist: Management of COVID-19. - Thomas S et al.
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.
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Preconditioning Strategies for Improving the Outcome of Fat Grafting. - Bonomi F et al.
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.