Low–molecular weight heparin (LMWH) is used clinically to treat clotting disorders. As an animal-sourced product, LMWH is a highly heterogeneous mixture, and its anticoagulant activity is not fully reversible by protamine. Furthermore, the reliability of the LMWH supply chain is a concern for regulatory agencies. We demonstrate the synthesis of heparin dodecasaccharides (12-mers) at the gram scale. In vitro experiments demonstrate that the anticoagulant activity of the 12-mers could be reversed using protamine. One of these, labeled as 12-mer-1, reduced the size of blood clots in the mouse model of deep vein thrombosis and attenuated circulating procoagulant markers in the mouse model of sickle cell disease. An ex vivo experiment demonstrates that the anticoagulant activity of 12-mer-1 could be reversed by protamine. 12-mer-1 was also examined in a nonhuman primate model to determine its pharmacodynamic parameters. A 7-day toxicity study in a rat model showed no toxic effects. The data suggest that a synthetic homogeneous oligosaccharide can replace animal-sourced LMWHs.

The interaction between carbon quantum dots (CQDs) and a single living cell was explored in real time. Here, we provide the quantitative data on the permeability of the HeLa cell membrane in the presence of CQDs with different surface functional groups (CQDs terminated with -OH/-COOH (CQD-OH), -PEG (CQD-PEG), and -NH2 (CQD-NH2)). Although these CQDs have very low toxicity towards HeLa cells, they still increase the cell membrane permeability by 8%, 13%, and 19% for CQD-PEG, CQD-OH, and CQD-NH2, respectively, and this kind of permeability was irreversible. These observations are valuable for promoting the bio-applications of carbon nanostructures in living systems.

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Chronic kidney disease (CKD) has become a global healthcare issue. CKD can progress to irreversible end-stage renal diseases (ESRD) or renal failure. e major risk factors for CKD include obesity, diabetes, and cardiovascular diseases. Understanding the key process involved in the disease development may lead to novel interventive strategies, which is currently lagging behind. Peroxisome proliferator-activated receptor c (PPARc) is one of the ligand-activated transcription factor superfamily members and is globally expressed in human tissues. Its agonists such as thiazolidinediones (TZDs) have been applied as effective antidiabetic drugs as they control insulin sensitivity in multiple metabolic tissues. Besides, TZDs exert protective effects in multiple other CKD risk disease contexts. As PPARc is abundantly expressed in major kidney cells, its physiological roles in those cells have been studied in both cell and animal models. e function of PPARc in the kidney ranges from energy metabolism, cell proliferation to inflammatory suppression, although major renal side effects of existing agonists (including TZDs) have been reported, which limited their application in treating CKD. In the current review, we systemically assess the function of PPARc in CKDs and the benefits and current limitations of its agonists in the clinical applications.