Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Metabolic reprogramming in childhood acute lymphoblastic leukemia

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades.  In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL. While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts.     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.     

The influence of different levels of dietary fat on the incidence and growth of MNU-induced mammary carcinoma in rats

This study describes the influence of isocalorically fed diets (containing different amounts of fat) on tumor incidence and parameters of fat metabolism in female Sprague-Dawley rats. Comparisons are made between rats induced with methylnitrosourea (25 mg/kg body wt) and untreated controls (Group I). The animals received either control diets (3.9% fat by weight, Groups I and II) or fat-enriched diets (10.7%, Group III; 15.6%, Group IV; 21.4%, Group V) over a period of 180 days. At the termination of the experiment, intake of the diet containing 10.7% fat by weight (24% fat per total calories) was associated with the highest tumor incidence. Comparing the different diets, liver lipid concentrations in the individual groups increased with increasing dietary fat, whereas the total lipid in plasma decreased. During the feeding period, total lipid of the liver and plasma, and plasma cholesterol, increased in all groups, but triglycerides of plasma decreased. However, when plasma cholesterol and triglycerides were calculated as a relative amount of total lipid in plasma, cholesterol was found to be significantly decreased in Groups III and IV, and triglycerides were increased in Group III but decreased significantly in Groups I, II, and V at the end of the experiment.     

Electron inelastic mean free path formula and CSDA-range calculation in biological compounds for low and intermediate energies.

In this study, for low atomic number targets and biological compounds, an inelastic mean free path (IMFP) formula and energy straggling parameter formula are presented, being valid for low and high electron energies. In addition, calculation of the continuous slowing down approximation-range (CSDA-range) from the stopping power is also made. The IMFP and the energy straggling parameter formulae are evaluated using the generalized oscillator strength (GOS) model and the exchange correction to the inelastic differential cross section (IDCS) given by Inokuti, M., [1978. Inelastic collisions of fast charged particles with atoms and molecules--the Bethe theory revisited. Rev. Mod. Phys. 50, 23-35]. The IMFP and CSDA-range for the biological compounds C5H5N5 (adenine), C5H5N5O (guanine), C4H5N3O (cytosine), C5H6N2O2 (thymine), C20H27N7O13P2 (cytosine-guanine) and C19H26N8O13P2 (thymine-adenine) have been introduced for incident electrons in the energy range 20 eV-1 MeV. The calculated results are compared with semi-empirical results and other theoretical results, good agreement being found with experimental data and Monte Carlo (PENELOPE code) predictions. All the IMFP versus energy curves exhibit minima around 80 eV.