Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells.

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

Flow cytometric assessment of leukocyte function in sickle cell anemia.

Sickle cell anemia is associated with susceptibility to infection due to hyposplenism and the reduced ability of neutrophils to kill pathogenic organisms. In this study, blood samples from sickle cell anemia patients were divided into two groups: the painful crisis group and the steady state group. Flow cytometric assessment of phagocytosis and burst formation of neutrophils and monocytes as well as basophil function were performed, and these were compared to those of age- and sex-matched normal control subjects. Neutrophils and monocytes in sickle cell anemia patients were significantly different from those in the normal control subjects in the areas of weaker phagocytosis, fewer ingested bacteria and reduced burst formation. Basophil degranulation was normal. This pilot study using flow cytometry explains in part the susceptibility to infection of sickle cell anemia patients despite their high neutrophil and monocyte counts.

Pattern of HB F level rise during normal pregnancies.

Fetal hemoglobin (Hb F) is the normal hemoglobin (Hb) that is present in the fetus and usually almost absent in adults. The objective of this study was to assess the changes in Hb F levels during normal pregnancy. The level of Hb F was determined in serial blood samples from women at different stages of pregnancy using cation exchange high performance liquid chromatography (HPLC) and compared to age and sex-matched controls. A significant increase (p <0.001) was observed in the level of maternal Hb F; the mean Hb F level during pregnancy was 0.71 +/- 0.51%, while in the non pregnant control group it was 0.28 +/- 0.35%. There was no significant difference in Hb F levels in the three trimester groups using the ANOVA test (F = 0.25). Correlation studies between the gestational age and level of Hb F showed no significant increase of Hb F with advancing pregnancy (R = -0.053, p >0.05). The cause of the rise in Hb F is yet to be elucidated.

Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial.

A randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care. The maximal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p < 0.05 for each comparison of tinzaparin vs. placebo). The decline in pain intensity was sharper for tinzaparin-treated patients, and complications consisted of two minor bleeding events that were reported and treated by cessation of tinzaparin. This investigation demonstrated that tinzaparin, administered at its approved treatment regimen, reduced the severity and duration of acute crisis of SCA.