Drug-induced retinal vein occlusion: a disproportionality analysis from the FDA adverse event reporting system (2004-2023).

Introduction: Retinal vein occlusion (RVO) often causes irreversible visual impairment, making early prevention crucial. This study aims to identify associations between different medications and RVO and provide information for clinical practice.

Method: This study included reports of RVO from the FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2023.

Effect of light-emitting diodes with different color rendering indexes on the ocular tissues of rat.

Aim: To compare the damage of light-emitting diodes (LEDs) with different color rendering indexes (CRIs) to the ocular surface and retina of rats.

Methods: Totally 20 Sprague-Dawley (SD) rats were randomly divided into four groups: the first group was normal control group without any intervention, other three groups were exposed by LEDs with low (LED-L), medium (LED-M), and high (LED-H) CRI respectively for 12h a day, continuously for 4wk. The changes in tear secretion (Schirmer I test, SIt), tear film break-up time (BUT), and corneal fluorescein sodium staining (CFS) scores were compared at different times (1d before experiment, 2 and 4wk after the experiment).

Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2.

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail.

DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl H-NMR probe.

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group.

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3).

Discovery of novel FFA4 (GPR120) receptor agonists with β-arrestin2-biased characteristics.

Background: Free fatty acid 4 (FFA4) (GPR120) receptor functions as a receptor for unsaturated long-chain free fatty acids by regulating the secretion of glucagon-like peptide-1 and suppressing the inflammatory process, in which these two distinct biological functions are modulated by two signaling pathways, Gq and β-arrestin2, respectively.

Results: By using pharmacophore modeling and virtual screening methods, several compounds are found with excellent activities for agonizing FFA4 receptor. It needs to be noted that among them, some molecules demonstrate appealing β-arrestin2-biased properties for the FFA4 receptor.

Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and (19)F-NMR.

Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance ((19)F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 'reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by (19)F-NMR.

The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes.

Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase.

Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known.

Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site.

The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases.