The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that has gained increasing attention in the field of dermatology due to its multifaceted role in skin health and ...disease. This review provides a comprehensive overview of the current state of knowledge regarding the AHR and its implications in dermatological conditions. The AHR is well known for its involvement in xenobiotic metabolism, particularly in response to polycyclic aromatic hydrocarbons and dioxins. However, recent research has unveiled its pivotal role in the skin immune response, barrier function, and homeostasis. The AHR signalling pathway is intricately linked to various dermatological disorders, including psoriasis, atopic dermatitis, acne and hidradenitis suppurativa. In this review, we delve into the molecular mechanisms through which AHR activation influences skin physiology and highlight how dysregulation can lead to pathological conditions. Moreover, we discuss the emerging therapeutic potential of AHR modulators in the treatment of skin diseases. In conclusion, the AHR is a pivotal player in dermatology, with a multifaceted role in skin physiology and pathology. Understanding the intricacies of AHR signalling in the skin offers promising avenues for the development of novel therapies and preventive strategies for various dermatological conditions. Further research is warranted to elucidate the full scope of AHR's contributions to dermatology and its potential as a therapeutic target.
Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of ...amyloid fibrils formed by the association of ACC
aggregation-prone peptides derived from the N-terminal region of insulin's A-chain. First, a large number of protofilament models composed of five copies of interacting ACC
peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibril structures. Finally, the amyloid fibril models resulting from the AA MD simulations were compared with atomic force microscopy (AFM) imaging experimental data. The obtained results indicate that the proposed multi-scale modeling procedure is capable of predicting protofilaments with high accuracy and may be applied for structure prediction and analysis of other amyloid fibrils.
Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug ...administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.
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