The function of the fibrinolytic system was first identified to dissolve fibrin to maintain vascular patency. Connections between the fibrinolytic system and many other physiological and pathological processes have been well established. Dysregulation of the fibrinolytic system is closely associated with multiple pathological conditions, including thrombosis, inflammation, cancer progression, and neuropathies. Thus, molecules in the fibrinolytic system are potent therapeutic and diagnostic targets. This review summarizes the currently used agents targeting this system and the development of novel therapeutic strategies in experimental studies. Future directions for the development of modulators of the fibrinolytic system are also discussed.

Glucose reacts with proteins nonenzymatically under physiological conditions. Such glycation is exacerbated in diabetic patients with high levels of blood sugar and induces various complications. Human albumin serum (HSA) is the most abundant protein in plasma and is glycated by glucose. The glycation sites on HSA remain controversial among different studies. Here, we report two protein crystal structures of HSA in complex with either glucose or fructose. These crystal structures reveal the presence of linear forms of sugar for both monosaccharides. The linear form of glucose forms a covalent bond to Lys-195 of HSA, but this is not the case for fructose. Based on these structures, we propose a mechanism for glucose ring opening involving both residues Lys-195 and Lys-199. These results provide mechanistic insights to understand the glucose ring-opening reaction and the glycation of proteins by monosaccharides.

A nanocomposite coupled with a photosensitizer (CPZ) and polyvinylpyrrolidone (PVP) based on LiYF ₄ :Yb/Er upconversion nanoparticles (UCNPs) was developed for efficient antimicrobial photodynamic therapy.

Malignant tumor (cancer) remains as one of the deadliest diseases throughout the world, despite its overall mortality drops. Nanomaterials (NMs) have been widely studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs, compared to small molecules, is that NMs can be concentrated passively in tumors through enhanced permeability and retention (EPR) effect. In the meantime, NMs can be engineered to target toward tumor specific markers in an active manner, e.g., receptor-mediated targeting. The relative contribution of the EPR effect and the receptor-mediated targeting to NM accumulation in tumor tissues has not been clearly defined yet. Here, we tackle this fundamental issue by reviewing previous studies. First, we summarize the current knowledge on these two tumor targeting strategies of NMs, and on how NMs arrive to tumors from blood circulation. We then demonstrate that contribution of the active and passive effects to total accumulation of NMs in tumors varies with time. Over time, the receptor-mediated targeting contributes more than the EPR effect with a ratio of 3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this review highlights the dynamics of active and passive targeting of NMs on their accumulation at tumor sites, and is valuable for future design of NMs in cancer diagnosis and treatment.

Plasminogen activator inhibitor-1 (PAI-1), together with its physiological target urokinase-type plasminogen activator (uPA), plays a pivotal role in fibrinolysis, cell migration, and tissue remodeling and is currently recognized as being among the most extensively validated biological prognostic factors in several cancer types. PAI-1 specifically and rapidly inhibits uPA and tissue-type PA (tPA). Despite extensive structural/functional studies on these two reactions, the underlying structural mechanism has remained unknown due to the technical difficulties of obtaining the relevant structures. Here, we report a strategy to generate a PAI-1·uPA(S195A) Michaelis complex and present its crystal structure at 2.3-Å resolution. In this structure, the PAI-1 reactive center loop serves as a bait to attract uPA onto the top of the PAI-1 molecule. The P4–P3′ residues of the reactive center loop interact extensively with the uPA catalytic site, accounting for about two-thirds of the total contact area. Besides the active site, almost all uPA exosite loops, including the 37-, 60-, 97-, 147-, and 217-loops, are involved in the interaction with PAI-1. The uPA 37-loop makes an extensive interaction with PAI-1 β-sheet B, and the 147-loop directly contacts PAI-1 β-sheet C. Both loops are important for initial Michaelis complex formation. This study lays down a foundation for understanding the specificity of PAI-1 for uPA and tPA and provides a structural basis for further functional studies.