Differentiation of Human Adipose-derived Stem Cells to Exosome-affected Neural-like Cells Extracted from Human Cerebrospinal Fluid Using Bioprinting Process.

BACKGROUND: Advancement in tissue engineering has provided novel solutions for creating scaffolds as well as applying induction factors in the differentiation of stem cells. The present research aimed to investigate the differentiation of human adipose-derived mesenchymal stem cells to neural-like cells using the novel bioprinting method, as well as the effect of cerebrospinal fluid exosomes. METHODS: In the present study, the extent of neuronal proliferation and differentiation of adipose- derived stem cells were explored using the MTT method, immunocytochemistry, and real-- time PCR in the scaffolds created by the bioprinting process. Furthermore, in order to investigate the veracity of the identity of the CSF (Cerebrospinal fluid) derived exosomes, after the isolation of exosomes, dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques were used. RESULTS: MTT findings indicated survivability and proliferation of cells in the scaffolds created by the bioprinting process during a 14-day period. The results obtained from real-time PCR showed that the level of MAP2 gene (Microtubule Associated Protein 2) expression increased on days 7 and 14, while the expression of the Nestin gene (intermediate filament protein) significantly decreased compared to the control. The investigation to confirm the identity of exosomes indicated that the CSF-derived exosomes had a spherical shape with a 40-100 nm size. CONCLUSION: CSF-derived exosomes can contribute to the neuronal differentiation of adipose- derived stem cells in alginate hydrogel scaffolds created by the bioprinting process.

Investigating the effect of Sulforaphane on AMPK/AKT/NRF2 pathway in human granulosa-lutein cells under H2O2-induced oxidative stress.

Excessive production of reactive oxygen species (ROS) in granulosa cells (GCs) plays a role in pathogenesis of polycystic ovarian syndrome (PCOS) by developing oxidative stress (OS). It was shown that Sulforaphane (SFN), with known antioxidant properties, can have protective effects in different diseases through affecting the nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway. Thus, the purpose of the current work was to examine the protective impact of SFN through the activation of the AMPK/AKT/NRF2 pathway against OS produced by H2O2 in granulosa-lutein cells (GLCs). Individuals' GLCs were obtained during ovum retrieval in intracytoplasmic sperm injection (ICSI) cycles. First, the induced OS model was created in GLCs using H2O2 exposure. To examine the protective effect of SFN against OS, the cells were cultured for 24 h in presence or absence of SFN. Eventually, the levels of intracellular ROS and apoptosis were measured by flow cytometry, and genes and proteins expression levels of AMPK, AKT, and NRF2 were evaluated using qRT-PCR and western blotting. Compared to the control group, the levels of intracellular ROS and apoptosis rose dramatically in GLCs with enhanced OS. SFN therapy decreased ROS and apoptosis levels and increased the overexpression of AMPK, AKT, and NRF2 genes and proteins. This study's results revealed that SFN exposure results in the alleviation of ROS and apoptosis levels possibly through activating the overexpression of genes and proteins of AMPK, AKT, and NRF2, and exerts its protective effects against OS in GLCs.

HES1 as an independent prognostic marker in esophageal squamous cell carcinoma.

BACKGROUND: Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21. AIMS: In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). METHODS: Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR). RESULTS: Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035). CONCLUSION: Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.

Lithium carbonate inducing disorders in three parameters of rat sperm.

BACKGROUND: Lithium has a significant impact in reducing the symptoms of bipolar mania but in long periods of use with therapeutic doses can cause several disorders in various organs including the reproductive system. In this study, the effect of lithium on the sperm concentration and motility and forms of abnormal cells has been examined. MATERIALS AND METHODS: Male Wistar rats under the 48-day treatment with lithium carbonate at doses of 10, 20, and 30 mg/kg bw/day were kept in standard conditions. At the end of this period, sperm cells isolated from the cauda epididymis were counted, motility was estimated, and stained with smear papanicolaou stain. RESULTS: In lithium-treated groups, the rate of spermatogenesis and sperm quality were reduced and was seen in a dose-dependent manner. DISCUSSION: Lithium alters intracellular signaling pathways such as inositol phosphate metabolic cycle and cyclic adenosine mono phosphate (cAMP) system and adenosine triphosphate (ATP) synthesis. It also interferes in the division of sex cells to produce mature sperm and showed changes in the sperm cell membrane, function, and structure.

The effect of aqueous cinnamon extract on the apoptotic process in acute myeloid leukemia HL-60 cells.

BACKGROUND: Acute promyelocytic leukemia (APL) is an acute leukemia diagnosed by translocation of chromosomes 15 and 17 [T (15,17)] and aggregation of neoplastic promyelocytes which are incapable of being converted into mature cells. Today, many tend to use medicinal herbs in studies and clinical applications for treatment of cancers. Cinnamon with scientific name "cinnamomumzelanicum" is a shrub of Laurales order, lauraceae family with cinnamomum genus. It is a medicinal shrub with anti-proliferation effect on tumor cells. This study was conducted to determine the effects of aqueous cinnamon extract on HL-60 cells as a model for APL. MATERIALS AND METHODS: In this in vitro experimental study, HL-60 cell line was cultured under the influence of cinnamon extract's concentrations of 0.01, 0.1, 1, and 2 mg/ml in with intervals of 24, 48, and 72 h. Growth inhibition and toxic effects of cinnamon extract were evaluated through tetrazolium salt reduction. The effect of this herb on the cell cycle was studied by flow cytometry. The Hoechst stain was used to detect apoptotic cell nuclei. RESULTS: Cinnamon extract inhibited the growth of HL-60 cells as correlated with concentration and time. After 72 h of treating HL-60 cells with 0.01 mg/l cinnamon extract, the growth of cells was inhibited by 90.1%. Cinnamon extract stopped the cell cycle in G1 phase and the Hoechst staining verified the apoptotic process in those cells. CONCLUSION: Considering the inhibitory property of cinnamon extract, we recommend it as a single drug or besides other medications for treating promyelocytic leukemia.