The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson’s trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages.

Premature Ovarian Failure; is characterized by the dysfunction or early depletion of ovarian reserves due to follicular loss in the ovary in women under age of 40. POF is the important cause of infertility and its etiology is still not clearly understood. Investigation of cell death mechanisms (CDM) that play a role in the follicular atresia (FA) triggered by excessive loss of granulosa cells (GCs) that provide metabolic support for oocyte and follicle development in the ovary will help to understand POF etiology. It was known that apoptosis and autophagy play a role in FA. Recent studies have shown that paraptosis, associated with endoplasmic reticulum stress (ERS), also exist in FA. POF model was established in C57BL/6 female mice by CTX and it was confirmed by increased follicle stimulating hormone (FSH), luteal hormone (LH) and decreased estradiol (E2) blood levels and follicle count. According to the results of the immunohistochemistry (IHC) cell death markers were significantly more expressed than control (C) and sham (S) groups in the POF model. In addition, more apoptotic cells were observed in the POF group compared to C and S in the TUNEL analysis. In consequence of this study apoptosis and autophagy as well as paraptosis play a role in the FA leading to POF, will help to develop new treatment protocols.

Cyclophosphamide (CTX), also known as cytophosphane among other, is a medication used as chemotherapy and to suppress the immune system. The PI3K/AKT/mTOR pathway is involved in the regulation of diverse cellular functions, including cell growth, protein synthesis, cell cycle regulation, glucose metabolism, and motility. In our study eight weeks old C57BL/6 female mice were divided into 3 groups as control (C), sham (S) and experimental group. The experimental group has been established with CTX treatment. No treatment was applied to the C group. The S group were given an equal amount of saline. CTX was administered intraperitoneally one every 2 days for 3 weeks; the first dose was 70 mg/kg, the ongoing doses were 30 mg/kg. At the end of 3 weeks mice were sacrificed and kidneys were taken for investigation. In order to show the effect of cyclophosphamide in kidney tissue, the tissues were stained via indirect immunohistochemistry with PI3K, AKT and mTOR primary antibodies. In our study, PI3K, AKT and mTOR expression levels were found to be significantly decreased in CTX-mediated mechanisms indicating that the mechanisms of CTX might involve in the inhibition of PI3K/AKT/mTOR signaling pathway.

The aim of this study was to determine the effects of Paclitaxel, Metformin and combined treatments on human breast cancer cell line MDA-MB-231 via TLR signaling pathway using immunocytochemical technique. MDA-MB-231 breast cancer cells were cultured in RPMI-1640 medium containing 10% FBS, 1% L-glutamine and 1% penicillin/streptomycin. Anti-TLR2, anti-TLR4, anti-MyD88, anti-NFkB, anti-IL-6 and anti-ERK primary antibodies were used for indirect immunohistochemistry after 24 h administrations of Paclitaxel, Metformin and combination of them. The mean values of the staining intensities (mild, moderate, strong and very strong) and percentage of positively stained cells were calculated using H-Score. The results showed that the immunoreactivities of TLR-2, TLR-4, MyD88, NFkB and ERK is increased after the drug treatments while the immunoreactivity of IL-6 has not changed between control and treated groups. To conclude that paclitaxel, metformin and combined therapies on breast cancer cells caused the activation of the TLR-MyD88-ERK signaling pathway which mediates tumor growth and progression, metastasis and drug resistance.