“Combination therapy”, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC₅₀ values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 µM, respectively, IC₅₀ of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 µM sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 µM of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 µM sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.

Intrauterine exposure to antiepileptic drugs (AEDs) is associated with neurodevelopmental alterations causing postnatal behavioral and cognitive alterations. These disorders are associated with the interference of these AEDs with the developing cerebral cortex and hippocampal neurons. Therefore, it is crucial to identify the drugs that should be avoided during pregnancy in order to prevent AED mediated developmental alterations. The present study was conducted to investigate the effects of prenatal exposure to the antiepileptic drug gabapentin (GBP) on the rat fetal brain during the organogenesis phase and to examine the potential ameliorative effect of ginger (Zingiber officinale). Consequently, the current study addressed the developmental neural changes on the histological, immuno-histochemical and ultrastructural levels. The brain of fetuses from the GBP group showed a highly significant decrease in their weight. Histologically, the cerebral cortex and hippocampus regions of fetuses maternally injected with GBP showed layer disorganization, vacuolated neuropil and massive cell degeneration. The expression of Caspase 3 was significantly increased in the brain of GBP fetuses, unlike the expression of Bcl-2 which was significantly decreased. On the ultrastructure level, the neurons showed pyknotic and chromatolytic nuclei. The cytoplasm was rarefied with swollen organelles. Co-administration of ginger evidently ameliorated most of these effects. In conclusion, GBP administration during pregnancy could possibly affect the developing fetal brain and ginger may have ameliorating effect against the induced GBP neurotoxicity and should be taken in parallel.

Previous studies have suggested that food dyes are responsible for causing number of health problems. The study under consideration aims to show the possible morphological and skeletal malformation induced due to in ovo administration of sunset yellow (SY) and tartrazine (Tz) with or without curcumin (Cur) during organogenesis of developing chick embryo at doses 1.575mg/egg, 0.375mg/egg and 3mg/kg eggs for SY, Tz and Cur comparing with control. The investigation revealed evident reduction in the weight and length of embryos as well as malformations in feather, head, and limbs. Most of the congenital malformations were seen in SY and Tz injected groups such as short beak, excencephaly, kniked tail and pygostyle, curved scapula and retardation in the degree of ossification were the most evident in endoskeleton malformation. In addition, the length of ossified long bones in SY and Tz groups was affected. Co-administration of Cur with SY and Tz ameliorate the reversed effect of SY and Tz on the shape, length, body weight and skeleton of embryos.

Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 ± 2.3 mmHg) compared with RUPP group (131.5 ± 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 ± 0.15 mg/dl (RUPP), 25.6 ± 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 ± 0.1 mg/dl (RUPP), 3.5 ± 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes.