A library of FRET-based peptides were prepared and studied as Thrombin substrates. This identified probes that showed selective activation by Thrombin, low fluorescent background signals, stability to Factor Xa, matrix metalloproteases, and primary human inflammatory cell lysates and supernatant. These were selected for further optimization, creating a second generation of fluorogenic probes with improved solubility and Plasmin resistance. The optimised probe allowed the detection of Thrombin activity in ex vivo fibrotic human tissue.
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http://dx.doi.org/10.1039/c7ob00663b | DOI Listing |
Arq Bras Oftalmol
January 2025
Ophthalmology and Visual Sciences Department, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Purpose: This study aimed to modify scleral contact lenses to achieve a desired compression standard and to evaluate the effectiveness and reliability of the adjustments.
Methods: In this nonrandomized, noncomparative, and partially masked study Scleral contact lens fittings were analyzed in 20 eyes of 12 patients (50% women, 50% men) diagnosed with keratoconus. Participants were selected based on their need for scleral contact lenses (SCLs), which was determined in complete ophthalmological examinations.
Acc Chem Res
January 2025
Department of Chemistry, Shanghai Key Laboratory of Catalysis and Innovative Materials, Center of Chemistry for Energy Materials Shanghai, Fudan University, Shanghai 200433, PR China.
ConspectusZinc metal batteries (ZMBs) appear to be promising candidates to replace lithium-ion batteries owing to their higher safety and lower cost. Moreover, natural reserves of Zn are abundant, being approximately 300 times greater than those of Li. However, there are some typical issues impeding the wide application of ZMBs.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Institut für Physiologie II, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Jena 07740, Germany.
In mammals, the four subunit isoforms HCN1-4 assemble to form functional homotetrameric and heterotetrameric hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels. Despite the outstanding relevance of HCN channels for organisms, including generating electrical rhythmicity in cardiac pacemaker cells and diverse types of brain neurons, key channel properties are still elusive. In particular, the unitary conductance, of HCN channels is highly controversial.
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