1. A Clot-Homing Near-Infrared Probe for In Vivo Imaging of Murine Thromboembolic Models
Dan Chen, Peiwen Liu, Yurong Liu, Zhiyou Wang, Yang Zhou, Longguang Jiang, Cai Yuan, Yongkun Li, Wei Lin, Mingdong Huang Adv Healthc Mater. 2022 Apr;11(8):e2102213. doi: 10.1002/adhm.202102213. Epub 2022 Jan 18.
Direct thrombus imaging contributes to early detection of thrombosis, and animal models with clinical relevance are vital in the development of new thrombolytics. Here, a facile clot-homing strategy is developed based on the finding that blood clot is negatively charged. Positively charged pentalysine moiety is coupled with phthalocyanine-based fluorophore , and its applications in murine thromboembolic models are described. The probe efficiently stains the cryosection of intracranial thrombi retrieved from patients with cardioembolic stroke. In vitro, the fibrin-rich clot is labeled by the probe at sub-nanomolar concentration. The probe-labeled clot is formed into microparticles (1-5 µm) and intravenously injected into mice for pulmonary embolism modeling. In vivo imaging demonstrates fast accumulation and retention of fluorescent clot microparticles in pulmonary vessels. Recombinant tissue-type plasminogen activator (rtPA) administration greatly reduces near-infrared signal in the lungs in a time-dependent manner. This probe is also tested in a stroke model. Middle cerebral artery is occluded by autologous thrombi formed under electric stimulation. In vivo imaging shows that the probe efficiently homes to thrombus at early stage. Hence, this probe has great potential in real-time imaging of thromboembolism in clinically relevant models, promoting bench-to-bedside translation. This clot-homing principle can be used in other applications.
2. Targeting motifs in frustule-associated proteins from the centric diatom Thalassiosira pseudonana
Neri Fattorini, Uwe G Maier Front Plant Sci. 2022 Oct 28;13:1006072. doi: 10.3389/fpls.2022.1006072. eCollection 2022.
The frustule of diatoms has an exceptional structure composed of inorganic and organic molecules. In the organic fraction, protein families were identified whose members are expected to have a complex cellular targeting to their final location within the frustule. Here we investigated for frustule-targeting signals two representatives of the cingulin family, the proteins CinY2 and CinW2; beside an already known, classical signal peptide, we have identified further regions involved in cellular targeting. By using these regions as a search criteria we were able to identify two new frustule proteins. In addition, we showed that the temporal regulation of the gene expression determines the final location of one cingulin. Our results therefore point to a sophisticated cellular and extracellular targeting of frustule components to build the fascinating frustule structure of a diatom.
