Review
Cell Biology
Manami Toriyama, Ken J. Ishii
Summary: The skin, as the largest organ of the human body, acts as a physical and immunological barrier against pathogen infection. There is still little known about which cells in human skin have primary cilia and how they change in response to immune reactions or disease. Several studies have described mechanisms of cilia regulation by immune reactions and the physiological relevance of cilia regulating proliferation and differentiation of stroma cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Dermatology
Mao-Qiang Man, Joan S. Wakefield, Theodora M. Mauro, Peter M. Elias
Summary: Nitric oxide (NO) plays a regulatory role in epidermal permeability barrier functions, affecting processes such as barrier homeostasis and wound healing. While insufficient NO can lead to disorders like diabetes and hypertension, excessive levels can induce cellular oxidative stress. iNOS remains essential for epidermal permeability barrier homeostasis.
EXPERIMENTAL DERMATOLOGY
(2022)
Review
Immunology
Yutaka Hatano, Peter M. Elias
Summary: Permeability barrier disruption can lead to immunological alterations, while inflammatory and immunological mechanisms can interrupt permeability barrier homeostasis. Changes in keratinocytes can cause both barrier dysfunction and immunological alterations, which are referred to as the intrinsic pathogenic mechanism. Molecules and pathways involved in this mechanism are important for disease pathogenesis and potential therapeutic targets for inflammatory cutaneous diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Li Yang, Karen A. Oppelt, Mary Jane Thomassen, Mona A. Marie, Shayan Nik Akhtar, Justin D. McCallen
Summary: COVID-19, caused by SARS-CoV-2, has a wide range of clinical manifestations from asymptomatic infection to severe pneumonia. GPR4, a pro-inflammatory GPCR highly expressed in vascular endothelial cells, could potentially be targeted to mitigate the inflammatory response and tissue injury associated with COVID-19.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Orsolya Somogyi, Zsolt Dajnoki, Lilla Szabo, Krisztian Gaspar, Zoltan Hendrik, Christos C. Zouboulis, Klaudia Docs, Peter Szucs, Katalin Dull, Daniel Torocsik, Aniko Kapitany, Andrea Szegedi
Summary: By comparing non-lesional HS skin, lesional HS skin, and healthy skin, the study found that none of the investigated molecules were significantly altered in non-lesional HS skin, while 11 molecules changed significantly in lesional HS skin. The study also showed that the permeability barrier function was not significantly damaged in HS skin, and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.
Article
Cell Biology
Romy Winkler, Marianne Quaas, Stefan Glasmacher, Uwe Wolfrum, Torsten Thalheim, Joerg Galle, Knut Krohn, Thomas M. Magin, Gabriela Aust
Summary: The expression and function of GPR115 in skin, specifically in epidermal differentiation, has been largely unknown. This study reveals that GPR115 is present in a small subset of keratinocytes in the stratified epidermis, and its expression is delayed in psoriatic skin. Deletion of GPR115 leads to reduced keratinocyte stratification, suggesting its role in epidermal differentiation. Intriguingly, endogenous GPR115 localizes along keratin filaments in a regular pattern, indicating a previously unknown function in regulating epidermal differentiation and keratin expression.
Review
Biochemistry & Molecular Biology
Wei-Cheng Fang, Cheng-Che E. Lan
Summary: Diabetes mellitus is a significant factor in chronic wounds and non-traumatic amputation, with increasing prevalence and cases worldwide. Keratinocytes, as the outermost layer of the epidermis, play a crucial role in wound healing. However, a high glucose environment disrupts the physiological functions of keratinocytes, leading to prolonged inflammation, impaired proliferation and migration of keratinocytes, and impaired angiogenesis. Understanding the molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments can aid in the development of effective and safe therapeutic approaches for promoting diabetic wound healing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biophysics
Harkanwalpreet S. Sodhi, Alyssa Panitch
Summary: A nanoparticle technology that utilizes electrostatic complexation with Dermatan sulfate (DS) has been developed to enhance and prolong the bioactivity of a MAP kinase 2 inhibitor peptide (MK2i). These DS-MK2i nanoparticles, prepared without stabilizing polymers or crosslinking, exhibit smaller particle size, lower polydispersity index, and specific zeta potential, as well as shelf stability and responsiveness to pH. They are also more effective than peptide alone in suppressing cytokine secretion in inflamed keratinocytes in the presence of serum, providing a convenient approach for peptide delivery in conditions like atopic dermatitis without serum-starvation in vitro testing.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Review
Biochemistry & Molecular Biology
Junghyun Park, Tae Joon Choi, Ki Sung Kang, Seo-Hyung Choi
Summary: This review explores the interrelationships between increased GI permeability and phlegm syndromes, discussing their similarities in symptoms, diseases, and herbal treatments. Both syndromes are related to inflammation and gut microbiota compositions, suggesting the need for further well-designed research in evidence-based integrative medicine.
Article
Immunology
ChunYan Yuan
Summary: IL-33 is a cytokine that modulates inflammation and immune responses, primarily associated with the development of Th2 immunological responses. It has been shown to be elevated in various autoimmune disorders, suggesting a role in inducing autoimmunity and inflammatory damage. The IL-33/ST2 axis holds promising potential as a therapeutic target for autoimmune disease treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Apor Veres-Szekely, Csenge Szasz, Domonkos Pap, Beata Szebeni, Peter Bokrossy, Adam Vannay
Summary: In the last 10 years, the relationship between dysbiosis and central nervous diseases has been proven. Microbial alterations lead to increased intestinal permeability, resulting in the penetration of bacterial fragments and toxins that induce local and systemic inflammatory processes, affecting distant organs including the brain. The integrity of the intestinal epithelial barrier plays a central role in the microbiota-gut-brain axis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Ye Liu, Pengfei Li, Tianci Jiang, Yue Li, Yu Wang, Zhe Cheng
Summary: Activation of EGFR pathway is involved in the pathogenesis of asthma, yet the specific mechanisms and pathways of EGFR signaling remain unclear. Inhibition of EGFR has shown potential in improving asthma pathology in experimental models, but translating these findings to clinical applications is challenging. Measures can be adopted to promote the clinical application of EGFR inhibitors. This review focuses on the role of EGFR in asthma pathogenesis and the development of a potentially novel therapeutic target for asthma.
RESPIRATORY MEDICINE
(2023)
Review
Medicine, Research & Experimental
Zeynab Kohandel, Tahereh Farkhondeh, Michael Aschner, Saeed Samarghandian
Summary: Astaxanthin (ATX) is a red pigment carotenoid found in shrimp, salmon, crab, and asteroidean, with proven antioxidant efficacy. Nrf2 plays a crucial role in mediating the various protective effects of ATX.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Xia Guo, Ayobami Olajuyin, Torry A. Tucker, Steven Idell, Guoqing Qian
Summary: BET proteins are epigenetic modulators that interact with acetylated lysine residues of histone proteins to regulate gene transcription. They play multiple roles in key cellular functions and are actively involved in various human lung diseases. The development of specific inhibitors targeting BET proteins has shown promising effects in preclinical models of lung diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Pureun-Haneul Lee, Seon Muk Choi, Min Hyeok An, Da Yeon Hwang, Shinhee Park, Ae Rin Baek, An-Soo Jang
Summary: This study discovered that Nectin4 levels in the blood of asthmatic patients were significantly increased and correlated with clinical variables. The experimental results indicated that Nectin4 is involved in airway inflammation and may serve as a therapeutic target in patients with asthma.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Dermatology
S. Leducq, S. Duchatelet, J. Zaragoza, S. Ventejou, A. de Muret, S. Eymieux, E. Blanchard, L. Machet, A. Hovnanian, T. Kervarrec
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2020)
Article
Dermatology
Emeline Riverain-Gillet, Helene Guet-Revillet, Jean-Philippe Jais, Marie-Nolle Ungeheuer, Sabine Duchatelet, Maia Delage, Thi Lam, Alain Hovnanian, Aude Nassif, Olivier Join-Lambert
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Review
Chemistry, Multidisciplinary
Simon J. de Veer, Andrew M. White, David J. Craik
Summary: Nature-derived cyclic peptides, exemplified by SFTI-1, serve as a rich source of inspiration for pharmaceutical design and synthetic chemistry. SFTI-1, with its unique biosynthetic pathway and potent inhibitory activity, is increasingly recognized for its applications in engineering inhibitors, studying inhibition mechanisms, grafting bioactive peptides, and evaluating peptidomimetic motifs and platform technologies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Dermatology
Olivier Gouin, Claire Barbieux, Florent Leturcq, Mathilde Bonnet des Claustres, Evgeniya Petrova, Alain Hovnanian
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Article
Medicine, Research & Experimental
Laure Guenin-Mace, Jean-David Morel, Jean-Marc Doisne, Angele Schiavo, Lysiane Boulet, Veronique Mayau, Pedro Goncalves, Sabine Duchatelet, Alain Hovnanian, Vincent Bondet, Darragh Duffy, Marie-Noelle Ungeheuer, Maia Delage, Aude Nassif, James P. Di Santo, Caroline Demangel
Article
Biochemical Research Methods
Kuok Yap, Junqiao Du, Fabian B. H. Rehm, Shyn Ric Tang, Yan Zhou, Jing Xie, Conan K. Wang, Simon J. de Veer, Linda H. L. Lua, Thomas Durek, David J. Craik
Summary: The protocol outlines a method for producing cyclic peptide precursors in Pichia pastoris that can be enzymatically matured into cyclic peptides, suitable for drug development and biotechnology applications. The process is versatile, allowing for the generation of cyclic peptides of varying classes and sizes, with production and purification taking approximately 24 days.
Article
Chemistry, Medicinal
Thomas Durek, Quentin Kaas, Andrew M. White, Joachim Weidmann, Abdullah Ahmad Fuaad, Olivier Cheneval, Christina Schroeder, Simon J. de Veer, Anita Dellsen, Torben Osterlund, Niklas Larsson, Laurent Knerr, Udo Bauer, Alleyn T. Plowright, David J. Craik
Summary: A new class of highly potent bivalent melanocortin receptor ligands has been designed based on nature-derived SFTI-1, showing substantial gains in agonist activity at human melanocortin receptors 1 and 3.
The most potent molecule, compound 6, exhibited low picomolar agonist activity at hMC1R and is at least 30-fold more selective for this receptor compared to hMC3R, hMC4R, or hMC5R.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Fabian B. H. Rehm, Tristan J. Tyler, Simon J. de Veer, David J. Craik, Thomas Durek
Summary: This study reports an engineered enzyme that accepts various nucleophile substrate mimetics, especially when a method to selectively inhibit the reactivity of byproducts is employed. In addition, C-terminal Leu-ethylenediamine motifs are identified as bona fide mimetics of native N-terminal sequences, enabling transpeptidase-catalyzed C-to-C ligations. This work significantly expands the synthetic scope of enzyme-catalyzed protein transpeptidation reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Dermatology
Helene Ragot, Alain Hovnanian
Summary: Drug repurposing has the potential to discover new treatments for diseases with high unmet medical needs. In this study, Lee et al. utilized transcriptomics and computational analysis to identify the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway as central in treating epidermolysis bullosa simplex. A pilot study using a topical mTOR inhibitor showed marked improvement.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Fabian B. H. Rehm, Tristan J. Tyler, Kuok Yap, Simon J. de Veer, David J. Craik, Thomas Durek
Summary: The study introduces a peptide/protein labeling strategy using an engineered transpeptidase to irreversibly incorporate diverse amines at a C-terminal asparagine, demonstrating its utility in preparing a protein-drug conjugate, generating a genetically inaccessible protein fusion, and site-specifically labeling both termini of a single protein in sequential steps.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Wenyu Liu, Simon J. de Veer, Yen-Hua Huang, Toru Sengoku, Chikako Okada, Kazuhiro Ogata, Christina N. Zdenek, Bryan G. Fry, Joakim E. Swedberg, Toby Passioura, David J. Craik, Hiroaki Suga
Summary: Cyclotides are plant-derived peptides with complex structures that have unique bioactivities and pharmaceutical potential due to their cyclic backbone and cystine knot core. A study using mRNA display identified potent cyclotide-based FXIIa inhibitors, with one inhibitor, cMCoFx1, showing high specificity and potency in inhibiting FXIIa. The interaction between cMCoFx1 and FXIIa at the contact interface suggests that cyclotides are promising cystine knot scaffolds for therapeutic development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Yue Wu, Zhenling Cui, Yen-Hua Huang, Simon J. de Veer, Andrey V. Aralov, Zhong Guo, Shayli V. Moradi, Alexandra O. Hinton, Jennifer R. Deuis, Shaodong Guo, Kai-En Chen, Brett M. Collins, Irina Vetter, Volker Herzig, Alun Jones, Matthew A. Cooper, Glenn F. King, David J. Craik, Kirill Alexandrov, Sergey Mureev
Summary: Advances in peptide and protein therapeutics have increased the demand for rapid and cost-effective polypeptide prototyping. A modified in vitro translation system allows efficient folding of disulfide-rich peptides and proteins in an aggregation-free and thermodynamically controlled environment.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Choi Yi Li, Fabian B. H. Rehm, Kuok Yap, Christina N. Zdenek, Maxim D. Harding, Bryan G. Fry, Thomas Durek, David J. Craik, Simon J. de Veer
Summary: This study demonstrates the use of light or streptavidin to tune the activity of knottin protease inhibitors. It shows that through activating a second mode of action, the inhibitory activity and selectivity of engineered knottins can be controlled against new targets. Additionally, the study identifies a position in the inhibitor's binding loop where a biotin tag can be inserted without impairing activity. Using streptavidin, biotinylated knottins with nanomolar affinity can be switched off in activity assays, and the anticoagulant activity of a factor XIIa inhibitor can be rapidly switched off in human plasma.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Dermatology
Justine Basset, Lucile Marchal, Alain Hovnanian
Summary: Pachyonychia congenita is a rare disorder characterized by painful palmoplantar keratoderma, and there is no standard treatment currently available. This study found that overexpression of EGFR ligands and EGFR signaling proteins is associated with PC lesions. Treatment with a drug targeting EGFR resulted in a significant reduction in pain and improvement in quality of life for patients with PC.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Chemistry, Medicinal
Sixin Tian, Thomas Durek, Conan K. Wang, Christina N. Zdenek, Bryan G. Fry, David J. Craik, Simon J. de Veer
Summary: Factor XIIa is a potential target for developing antithrombotic drugs, and MCoTI-II is a promising candidate for FXIIa-targeted anticoagulants. By engineering the cyclization loop of MCoTI-II, more potent FXIIa inhibitors have been generated. One variant with five residues in loop 6 exhibited high selectivity, stability in human serum, and the ability to block the intrinsic coagulation pathway in human plasma.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
