Extracellular Circulation Research Articles

Circulating Mitochondrial DNA as a Diagnostic Biomarker for Predicting Disease Severity in Patients With Acute Pancreatitis

Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions with up to 40% mortality in moderate to severe AP. 1 Boxhoorn L. et al. Lancet. 2020; 396: 726-734 Abstract Full Text Full Text PDF PubMed Scopus (221) Google Scholar Cell death and inflammation are key processes in the pathophysiology of AP, and mitochondria-mediated cell death plays a central role in the initiation of inflammatory pathways of AP. 2 Krysko D.V. et al. Trends Immunol. 2011; 32: 157-164 Abstract Full Text Full Text PDF PubMed Scopus (483) Google Scholar Evidence suggests that several damage-associated molecular patterns (DAMPs) are released from dead pancreatic acinar mitochondria into the extracellular circulation. Given the need for early diagnosis of AP severity for proper treatment, we investigated whether circulating levels of mitochondrial DNA (mtDNA) fragments are a potential biomarker of early distinction for AP severity.

Redox poly(ethylene glycol)-b-poly(L-lactide) micelles containing diselenide bonds for effective drug delivery.

Bioreducible polymers have appeared as the ideal drug carriers for tumor therapy due to their properties of high stability in extracellular circulation and rapid drug release in intracellular reducing environment. Recently, the diselenide bond has emerged as a new reduction-sensitive linkage. In this work, the amphiphilic poly(ethylene glycol)-b-poly(L-lactide) containing diselenide bond has been synthesized and used to load anti-tumor drug, docetaxel (DTX), to form the redox micelles. It was found that the redox micelles showed a rapid response to glutataione (GSH), which resulted in a fast release of DTX in the presence of GSH. In contrast, <40% of DTX was released from the micelles within 72h under the normal condition (absence of GSH). The DTX-loaded redox micelles showed the significant inhibition effect to MCF-7 cells, and the cytotoxicity was dependent on the intracellular GSH concentrations. Moreover, considering the potentially clinical applications of the micelles through intravenous injection, the blood compatibility was also studied by the hemolysis analysis, activated partial thromboplastin time, prothrombin time and thromboelastography assays. These results confirmed that the redox micelles showed good blood safety, suggesting a potential application in tumor therapy.

A Unique Intracellular, Extracellular and Transmembrane Circulation of Potassium Ions in the Auditory Inner Ear as an Anticarcinogenic Principle? Part 1

A total of 4668 patients from four university hospitals, all representing cases with inner ear tumours or other inner ear disorders were evaluated. No primary cancer or melanoma could be detected. These results are in compliance with publications of other institutions discussing their own results in detecting inner ear pathologies. This finding is unusual and leads to the assumption that the epithelial cells of the auditory inner ear may be protected from malignant transformations. The aim of this study is to investigate the reasons for this supposed anticarcinogenic privilege of the auditory inner ear. The auditory inner ear has some unique features in the organism by reversing the relationship between intra- and extracellular ion concentrations of potassium and sodium in the endolymph. Furthermore it has a physiologically extremely high membrane potential and an unusual transmembrane and extracellular circulation of potassium ions. How these aspects contrast with the corresponding features at the carcinoma site, will be investigated. This comparison will be further deepened by reviewing the published actions of antitumoral substances in connection with these issues. On the basis of this comparative study one might speculate that the auditory inner ear is privileged by an anticarcinogenic principle and that the specific features of membrane potential, certain potassium channels and the unique transmembrane as well as extracellular potassium movements may play a decisive role in it.