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PD-1/PD-L1 protein complex is attracting a great deal of interest as a drug target for the design of immune therapies able to block its assembly. Although some biologic drugs have entered clinical use, their poor response rate in patients are demanding further efforts to design small molecule inhibitors of PD-1/PD-L1 complex with higher efficacy and optimal physicochemical properties. Dysregulation of pH in the tumor microenvironment is indeed one of the key mechanisms promoting drug resistance and lack of response in cancer therapy. Integrating computational and biophysical approaches, herein we report a screening campaign that has led to identifying VIS310 as a novel ligand of PD-L1, with physicochemical properties enabling a pH-dependent binding potency. Additional optimization efforts by analogue-based screening have been instrumental to disclosing VIS1201, which exhibits improved binding potency against PD-L1 and is able to inhibit PD-1/PD-L1 complex formation in a ligand binding displacement assay. While providing preliminary structure–activity relationships (SARs) of a novel class of PD-L1 ligands, our results lay the foundation for the discovery of immunoregulatory small molecules resilient to tumor microenvironmental conditions for escaping drug-resistance mechanisms. [ABSTRACT FROM AUTHOR]

Over the last two decades, indoleamine 2,3-dioxygenase 1 (IDO1) has attracted wide interest as a key player in immune regulation, fostering the design and development of small molecule inhibitors to restore immune response in tumor immunity. In this framework, biochemical, structural, and pharmacological studies have unveiled peculiar structural plasticity of IDO1, with different conformations and functional states that are coupled to fine regulation of its catalytic activity and non-enzymic functions. The large plasticity of IDO1 may affect its ligand recognition process, generating bias in structure-based drug design campaigns. In this work, we report a screening campaign of a fragment library of compounds, grounding on the use of three distinct conformations of IDO1 that recapitulate its structural plasticity to some extent. Results are instrumental to discuss tips and pitfalls that, due to the large plasticity of the enzyme, may influence the identification of novel and differentiated chemical scaffolds of IDO1 ligands in structure-based screening campaigns. [ABSTRACT FROM AUTHOR]

Nowadays, bioactive compounds from vegetable food and waste are of great interest for their inhibitory potential against digestive enzymes. In the present study, the inhibitory activity of methanolic extract from Lycium barbarum leaves on porcine pancreas α-amylase has been studied. The α-amylase inhibitory activity of the constituent phenolic acids was also investigated. The leaves were extracted by ultrasound-assisted method, one of the most efficient techniques for bioactive extraction from plant materials, and then the phenolic acids were identified by Accurate-Mass Quadrupole Time-of-Flight (Q-TOF) Liquid Chromatography/Mass Spectrometry (LC/MS). Chlorogenic and salicylic acids were the most abundant phenolic acids in L. barbarum leaf extract. The inhibitory effect against α-amylase, determined for individual compounds by in vitro assay, was higher for chlorogenic, salicylic, and caffeic acids. L. barbarum leaf extract showed an appreciable α-amylase inhibitory effect in a concentration-dependent manner. Docking studies of the considered phenolic acids into the active site of α-amylase suggested a conserved binding mode that is mainly stabilized through H-bonds and π-π stacking interactions. [ABSTRACT FROM AUTHOR]

Athletes are among a unique group such that they may possess a serious underlying pathologic condition that may often go unnoticed given their high caliber of physical fitness. However, several considerations should be investigated, especially in the perioperative period, in order to minimize morbidity and mortality. Namely, cardiac pathologic condition can result in sudden death, and pulmonary pathologic condition may affect airway and respiratory management. Moreover, patients undergoing orthopedic surgery are at the highest risk for venous thromboembolism. Regardless of the condition, it is crucial to be vigilant and explore the unique medical considerations for the athlete undergoing anesthesia., Competing Interests: Disclosure The authors of the current study certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abdominal aortic aneurysm (AAA) is a prevalent vascular disease with high mortality rates upon rupture. Despite its prevalence in elderly populations, there remain limited treatment options; invasive surgical repair, while risky, is the only therapeutic intervention with proven clinical benefits. Dietary factors have long been suggested to be closely associated with AAA risks, and dietary therapies recently emerged as promising avenues to achieve non-invasive management of a wide spectrum of diseases. However, the role of dietary therapies in AAA remains elusive. In this article, we will summarize the recent clinical and pre-clinical efforts in understanding the therapeutic and mechanistic implications of various dietary patterns and therapeutic approaches in AAA., Competing Interests: Author BW is the corresponding author, the coordinator for this research topic, and has recused from the peer-review and editorial processes. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Gregg, Riccio, Hoyt, Islam, Ahn, Le, Patel, Zhang, He, McKinney, Kent and Wang.)