Dual-action platinum(II) Schiff base complexes : photocytotoxicity and cellular imaging

Nine photo-stable Pt(II) Schiff base complexes [Pt(O^N^N^O)] (Pt1–Pt9) containing tetradentate salicylaldimine chelating ligands have been synthesized and characterized as potential photosensitisers for photodynamic therapy (PDT). The effects of electron-withdrawing versus electron-donating substituents on their electronic spectral properties are investigated. Pt1–Pt9 show broad absorption bands between 400–600 nm, which makes them useful for green-light photodynamic therapy. The complexes showed intense phosphorescence with emission maxima at ca. 625 nm. This emission was used to track their cellular localization in cancer cells. Confocal cellular imaging showed that the complexes localized mostly in the cytoplasm. In the dark, the complexes were non-toxic to A549 human lung cancer cells, but exhibited high photo-toxicity upon low-dose green light (520 nm, 7.02 J/cm2) irradiation via photo-induced singlet oxygen generation. Thus, these photoactive Pt(II) complexes have the potential to overcome the problem of drug resistance and side effects of current clinical Pt(II) drugs, and to act as both theranostic as well as therapeutic agents

Learn to Propagate Reliably on Noisy Affinity Graphs

Recent works have shown that exploiting unlabeled data through label propagation can substantially reduce the labeling cost, which has been a critical issue in developing visual recognition models. Yet, how to propagate labels reliably, especially on a dataset with unknown outliers, remains an open question. Conventional methods such as linear diffusion lack the capability of handling complex graph structures and may perform poorly when the seeds are sparse. Latest methods based on graph neural networks would face difficulties on performance drop as they scale out to noisy graphs. To overcome these difficulties, we propose a new framework that allows labels to be propagated reliably on large-scale real-world data. This framework incorporates (1) a local graph neural network to predict accurately on varying local structures while maintaining high scalability, and (2) a confidence-based path scheduler that identifies outliers and moves forward the propagation frontier in a prudent way. Experiments on both ImageNet and Ms-Celeb-1M show that our confidence guided framework can significantly improve the overall accuracies of the propagated labels, especially when the graph is very noisy.Comment: 14 pages, 7 figures, ECCV 202

Biotinylated photoactive Pt(IV) anticancer complexes

Novel biotinylated diazido-Pt(IV) complexes exhibit high visible light photocytotoxicity while being stable in the dark. Photocytotoxicity and cellular accumulation of all-trans-[Pt(py)2(N3)2(biotin)(OH)] (2a) were enhanced significantly when bound to avidin; irradiation induced dramatic cellular morphological changes in human ovarian cancer cells treated with 2a

Extending the Excitation Wavelength of Potential Photosensitizers via Appendage of a Kinetically Stable Terbium(III) Macrocyclic Complex for Applications in Photodynamic Therapy

The development of viable photodynamic therapy protocols is often hindered by photosensitizers that require high-energy UV irradiation that has limited potential for clinical use due to its low tissue penetration. Herein, we report a strategy for extending the excitation wavelength of potential photosensitizers via the covalent attachment of a terbium(III)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate complex (DO3A-Tb). The method was systematically demonstrated with a series of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, anthracene, pyrene, and fluoranthene) to prepare six new complexes (Tb1-Tb6) with bathochromic shifts that extended into the visible region. Determination of their quantum yields for singlet oxygen (1O2) production at 350 and 420 nm showed significant enhancements from the parent molecule in all cases. Cell viability studies on cervical cancer cells (HeLa) and noncancerous MRC-5 cells showed no measurable cytotoxicity for all complexes prior to light irradiation. However, after irradiation at 420 nm (20 min, 9.27 J cm-2), Tb3-Tb6 were phototoxic to HeLa cells with IC50 values between 14.3-32.3 μM. Cell morphological studies and fluorescence microscopy with live/dead cell stains confirmed these findings. In addition, these complexes were highly stable in human blood plasma, with no significant degradation observed after 96 h at 37 °C. This excellent phototoxicity profile and high stability in blood plasma, coupled with the moderately lipophilic nature of the complexes, favorably indicate the potential of DO3A-Tb as a heavy atom-bearing moiety for modification of potential photosensitizers into ideal phototherapeutic drug candidates with longer excitation wavelengths for in vivo application.</p

Day 3 neutrophil-to-lymphocyte ratio and its derived indices predict 90-day poor outcomes following mechanical thrombectomy in acute ischemic stroke patients

ObjectiveTo investigate the dynamic changes in neutrophil–to–lymphocyte ratio (NLR) and its derived indices following mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and evaluate their predictive value for prognosis.MethodsThis single-center retrospective cohort study included AIS patients who underwent MT at Zhongshan Hospital of Xiamen University from January 2018 to February 2024. Peripheral blood samples were collected on admission, day 1, and day 3 after MT to determine the NLR, derived NLR (dNLR), and neutrophil–monocyte–to–lymphocyte ratio (NMLR). The primary endpoint was poor functional outcome at 90 days (modified Rankin scale score 3–6). The secondary endpoints included post-operative hemorrhagic transformation, malignant cerebral edema, in-hospital mortality, and 90-day all-cause mortality. Receiver operating characteristic (ROC) curve analysis was used to evaluate predictive performance, and multivariate logistic regression models were employed to explore the independent associations between inflammatory markers and prognosis.ResultsA total of 423 eligible patients were included. Both groups showed similar dynamic trends in inflammatory markers, peaking on day 1 post-MT and subsequently declining. However, the poor outcome group (n = 255, 60.28%) maintained higher levels on day 3, whereas the good outcome group showed a significant decreasing trend. ROC curve analysis revealed that the NLR (AUC = 0.85, 95% CI: 0.81–0.89), dNLR (AUC = 0.86, 95% CI: 0.82–0.89), and NMLR (AUC = 0.85, 95% CI: 0.81–0.89) on day 3 post-MT had the strongest predictive power for 90-day poor outcomes. After comprehensive adjustment for confounders, these inflammatory markers were independently associated with 90-day poor outcomes: for each unit increase in the NLR, the risk of poor outcome increased by 38% (OR = 1.38, 95% CI: 1.28–1.49, p &lt; 0.001); for dNLR, it increased by 104% (OR = 2.04, 95% CI: 1.73–2.40, p &lt; 0.001); and for NMLR, it increased by 35% (OR = 1.35, 95% CI: 1.26–1.45, p &lt; 0.001).ConclusionInflammatory markers (NLR, dNLR, and NMLR) on day 3 post-MT can serve as independent predictors of prognosis in AIS patients treated with MT. Dynamic monitoring of inflammatory markers may facilitate early risk stratification and guide individualized treatment strategies

Chirality in metal-based anticancer agents

Chiral metal-based drugs are currently an interesting and rapidly growing field in anticancer research. Here the different chiral metal-based anticancer agents and the extent to which the chiral resolution affects their biological properties are discussed. This review will aid the design of new potent and efficient chiral metal-based anticancer drugs that exploit the unique properties combined with their potential selectivity toward targeted chiral biomolecules.</p