Mammalian target of rapamycin (mTOR) is a member of the PI3K/Akt/mTOR signaling pathway that participates in cell growth, proliferation, protein synthesis, transcription, angiogenesis, apoptosis and autophagy. We investigated the role of mTOR and other signaling molecules in the rat uterus during implantation. Female pregnant rats were divided into three groups: embryonic days (ED) 4.5, 5.5 and 6.5 according to vaginal smears. Immunohistochemical staining of mTORC1, mTORC2, IGF1, PI3K, pAkt1/2/3, ERK1 and pERK1/2 was performed on formalin fixed, paraffin embedded uterine tissue samples. pAkt1/2/3 and ERK1 also were analyzed using western blotting. We found that PI3K/Akt/mTOR and ERK/pERK were increased during the implantation period. Different amounts of mTORC1, mTORC2, IGF1, PI3K, pAKT1/2/3, ERK1 and pERK1/2 were expressed in luminal epithelium, decidual cells, embryoblast and trophoblast cells during implantation. We suggest that mTOR and associated signaling molecules may participate in implantation.

Nesfatin-1 and neuronostatin in the central nervous system participate in regulating stress responses. Glucocorticoid hormones affect the brain through glucocorticoid receptors (GR). We investigated in the rat the possibility of co-localizing nesfatin-1 and neuronostatin neurons in hypothalamic areas with GR. using immunohistochemistry. We counted nesfatin-1 and neuronostatin stained neurons. We counted GR positive nesfatin-1 neurons in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) and GR positive neuronostatin neurons in the periventricular nucleus (PeN). The percentage of nesfatin-1 neurons that expressed GR was 38.4% in female rats and 21.9% in male rats in the ARC, and 33.3% in female rats and 29.2% in male rats in the PVN. The percentage of neuronostatin neurons that expressed GR was 39.1% in female rats and 39.9% in male rats in the PeN. We found that a substantial portion of nesfatin-1 and neuronostatin neurons were stained for GR. We speculate that the pattern of GR might permit secretion of neuropeptides to be stimulated by peripheral glucocorticoid signals. Stress can suppress food intake, in part, through the GR in neurons that express nesfatin-1, which is a satiety molecule, and in neurons that express neuronostatin, which is an anorexigenic peptide.

Investigation of the effects of rapamycin on the mTOR pathway and apoptosis in metastatic and non-metastatic human breast cancer cell lines

Objective: The aim of the study to show the relation of T cells in placental villous fragments with FOXP3,JAK1 and STAT5 receptors in different conditions such as GDM, PE and IUGR placental tissues. Methods: Specimens of ten(10) diabetic placentas, ten(10) preeclamptic, ten(10) intrauterine growth restricted placentas and ten(10) control placentas were collected by systematic uniform random sampling. Immunohistochemical detections of FOXP3, JAK1 and STAT5 were performed in histological sections for each group’s placental tissue. The H-score value was derived for each specimen by calculating the sum of the percentage of syncytiotrophoblast and syncytial nodes in placenta and intervillus area. They were categorized by intensity of staining, multiplied by its respective score. Results: FOXP3, JAK1 and STAT5 immunoreactivity comparisons are shown in four groups of placentas. FOXP3 immunoreactions significantly increase in GDM group. JAK1 and STAT5 immunoreactions significantly decrease in PE group. STAT5 immunoreactivity was detected crucially increase in GDM group. Discussion: The results showed that in different conditions such as PE,GDM and IUGR, T cells in placental villous fragments have relation with FOXP3,JAK1 and STAT5 receptors and that FOXP3 can inactivate the PE and IUGR in the placental tissue. We have also confirmed as other studies that JAK-STAT pathway plays important role in PE,IUGR and GDM placental tissue.

Objective: Lung cancer is characterized by uncontrolled proliferation, loss of apoptosis, angiogenesis, and metastatic potential. Caffeic acid phenethyl ester (CAPE), the major bioactive molecule of propolis, and epigallocatechin gallate (EGCG), a essential polyphenol of green tea, have documented antioxidant, anti-proliferative, and anti-angiogenic effects. This study aimed to investigate the effects of EGCG and CAPE on VEGF and the PI3K/Akt/mTOR signaling pathway, key regulators of lung cancer progression, using in silico and in vitro models. Methods: This study Lung cancer cells (DSMZ/ACC-234) was conducted to demonstrate the inhibition of cell proliferation by the MTT method, molecular binding via autodock vina and protein expression by immunohistochemistry analysis, targeting the VEGF and PI3K/Akt/mTOR pathways with CAPE and EGCG treatment. Results: EGCG and CAPE treatments significantly reduced cell proliferation in lung cancer cells. Untreated cells exhibited strong to very strong immunoreactivity for VEGF and PI3K/Akt/mTOR pathway markers, whereas EGCG reduced these signals to mild–moderate levels and to CAPE moderate–strong levels. Since both treatments resulted in a statistically significant increase in mTORC1 immunoreactivity, molecular docking targeting was performed via it. Conclusion: EGCG and CAPE exhibit significant anti-proliferative and anti-angiogenic effects by adjusting the VEGF and PI3K/Akt/mTOR signaling pathways in lung cancer cells. mTORC1 activation molecular binding affinity is higher in the CAPE-treated group compared to the EGCG group. These findings highlight the therapeutic importance of targeting these pathways in developing novel treatment strategies for lung cancer.