We developed a 2D multi-agent stochastic model of interaction between cellular debris, bacteria and neutrophils in the surface cutaneous wound with local hypoxia. Bacteria, which grow logistically with a maximum carrying capacity, and debris are phagocytosed by neutrophils with probability determined by the partial pressure of oxygen in the tissue, pO 2 = 4-400 mmHg, according to the Michaelis-Menten equation with K m = 40 mmHg. The influx of new neutrophils depends linearly (k = 0.05-0.2) on the amount of (a) platelets and (b) neutrophils, which are in contact with bacteria or debris. Each activated neutrophil can accomplish a certain amount of phagocytosis, n max = 5-20, during its lifespan, T = 1-5 days. The universe of outcomes consists of (a) bacteria clearance (high k and n max ), (b) infection is not cleared by neutrophils (low k and nmax), and (c) intermittent (quasiperiodic) bursts of inflammation. In the absence of infection, phagocytosis stops within 48 h. We found that pO 2 alone did not change the type of outcome, but affects the number of recruited neutrophils and inflammation duration (in the absence of infection by up to 10 and 5 %, respectively).

01 Jul 2015·Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

A eudesmane-type sesquiterpene isolated from Pluchea odorata (L.) Cass. combats three hallmarks of cancer cells: Unrestricted proliferation, escape from apoptosis and early metastatic outgrowth in vitro

Article

Author: Jäger, Walter ; Urban, Ernst ; Atanasov, Atanas Georgiev ; Krieger, Sigurd ; Schelch, Karin ; Frisch, Richard ; Krupitza, Georg ; Nguyen, Chi Huu ; Feistel, Björn ; Holzner, Silvio ; Zehl, Martin ; Zupko, Istvan ; Kopp, Brigitte ; Blaschke, Michael ; McKinnon, Ruxandra ; Diaz, Rene ; Grusch, Michael ; Ecker, Gerhard F ; Dirsch, Verena M

Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated disorders. The dichloromethane extract (DME) was tested in the carrageenan-induced rat paw oedema assay investigating its effect on inflammation that was inhibited by 37%. Also an in vitro anti-neoplastic potential was reported. However, rather limited information about the bio-activity of purified compounds and their cellular mechanisms are available. Therefore, two of the most abundant eudesmanes in P. odorata were isolated and their anti-neoplastic and anti-intravasative activities were studied. HL-60 cells were treated with P. odorata compounds and metabolic activity, cell number reduction, cell cycle progression and apoptosis induction were correlated with relevant protein expression. Tumour cell intravasation through lymph endothelial monolayers was measured and potential causal mechanisms were analyzed by Western blotting. Compound PO-1 decreased the metabolic activity of HL-60 cells (IC50 = 8.9 μM after 72 h) and 10 μM PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic activities at concentrations beyond 100 μM. PO-1 arrested the cell cycle in G1 and this correlated with induction of JunB expression. Independent of this mechanism 25 μM PO-1 decreased MCF-7 spheroid intravasation through the lymph endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs unrestricted proliferation and induces apoptosis at low micromolar concentrations. These results warrant further testing in vivo to challenge the potential of PO-1 as novel lead compound.

01 Jan 1995·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Effects of Steroidal Glycosides on Blood Glucose in Normal and Diabetic Mice.

Q4 · MEDICINE

Article

Author: Toshihiro Miura ; Atsushi Kato ; Tomoji Fukunaga

Two steroidal glycosides, PO-1 and PO-2, were tested as a new hypoglycemic drug. PO-2 showed remarkable hypoglycemic activity on i.p. injection into normal mice. PO-1 slightly lowered the blood glucose in normal mice. Furthermore, PO-1 and PO-2 exhibited significant hypoglycemic effects in streptozotocin-induced diabetic mice. However, a steroid, diosgenin, did not affect the blood glucose level in either normal or streptozocin-induced diabetic mice, indicating that the branching glucose units are essential for the biological activity.

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Indication	Highest Phase	Country/Location	Organization	Date
Acinetobacter Baumannii Infection	Preclinical	Spain	Telum Therapeutics SLStartup	27 Dec 2023

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