Impact of metformin on neocortical development during pregnancy: Involvement of ERK and p35/CDK5 pathways.

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.

Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells.

Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.

Antrodia salmonea extract inhibits cell proliferation through regulating cell cycle arrest and apoptosis in prostate cancer cell lines.

Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.

Antibacterial effects of saliva substitutes containing lysozyme or lactoferrin against Streptococcus mutans.

OBJECTIVE: To determine the antibacterial effects of different saliva-substitutes-containing-lysozyme(LYZ) or-lactoferrin(LF) on Streptococcus mutans(S. mutans) in comparison with human saliva. DESIGN: In vitro wound-healing assay was performed with L929 mouse fibroblast cell line by using various concentrations of LYZ and LF to determine optimum concentrations and to confirm do not show any cytotoxicity of proteins according to cell culture studies. Antibacterial effect was assessed by determining Minimum Inhibitory Concentrations for all groups on S.mutans. Bacterial adhesion of S. mutans for 4 h on hydroxyapatite(HAP) discs after application of different saliva substitutes was evaluated. The formulations were:saliva-substitute(Group SS);saliva-substitute-containing-Lactoferrin(Group SSLF);saliva-substitute-containing-Lysozyme(Group SSLYZ). Human saliva was control group(Group HS). RESULTS: In vitro wound healing assay results showed that, when added into the cell culture media, LYZ and LF significantly increase 48 -h scratch wound closure compared to the cell culture media(p < 0.0001). At the end of second day, samples treated with both between 2.5-100 µg/mL LF and 5-200 µg/mL LYZ were found to have significant wound healing effect(p < 001). It was observed that saliva-substitutes-containing-LYZ or-LF had antibacterial effects on S.mutans. Bacterial adhesion on HAP discs was observed significantly higher in control group than in study groups. The amount of adhered S. mutans was significantly higher in Group SS than other study groups(p < 0.0001). However, no statistically significant difference was found between the number of bacteria adhered to HAP discs between SSLYZ and SSLF groups(p > 0.05). CONCLUSIONS: The study of cell viability and wound healing was great significance in the optimum concentrations of LYZ and LF. Among formulations, saliva-substitutes-containing-LYZ or-LF exhibited higher inhibitory effect on S.mutans.

Explaining different orientations to the 2013 Gezi Park demonstrations in Istanbul, Turkey.

Although a notable minority orient to real-world demonstrations by actively participating, other less involved, safer, orientations are more frequent. Thus, in the context of anti-government demonstrations in Gezi Park/Taksim Square in Istanbul, Turkey, in 2013, we distinguished between the orientations of participating, visiting, and watching. Study 1 (N = 359) and Study 2 (N = 327) confirmed that participating was characterized by greater experience of police violence and feelings of collective empowerment (Drury & Reicher, European Journal of Social Psychology, 35, 2005, 35) than visiting and watching the demonstrations. Expanding upon and replicating the findings from Study 1, Study 2 examined identification with protestors and left-wing ideology, along with constructs (social support, anger at the government, protestor's efficacy, endorsement of protestors) from the dynamic dual pathway model (van Zomeren et al., Personality and Social Psychology Review, 16, 2012, 180) as predictors of the three different orientations to the demonstrations. As expected, the dynamic dual pathway model predicted reported participation via endorsement of protestors, independent of identification with protestors and left-wing ideology.

Suppression of bromodomain-containing protein 4 by shRNA: A new approach for cancer treatment.

PURPOSE: MYC is a transcription factor coding gene that is believed to control 15% of the genes in the entire human genome. The central role of c-MYC in cancer pathogenesis makes it a major therapeutic target in field of anticancer agent development. METHODS: We targeted the acetyl-lysine binding modules or bromodomains, which are associated with c-MYC transcriptional activation. RESULTS: Sequence specific inhibition of BET bromodomains with small hairpin RNAs (shRNAs) resulted in cessation of cellular proliferation in different cancer cell lines. Unlike previous studies on inhibition of bromodomains with selective small-molecule inhibitors, our study revealed the significant role of BET bromodomains in solid tumours and also highlighted the ease of RNA interference (RNAi) methodology for inhibition of bromodomain translation. CONCLUSION: The degree of influence of BET bromodomain inhibition on proliferation in five cancer cell lines established it as the major target in malignancies characterized by activation of c-MYC.

Does Body Image Affect Quality of Life?: A Population Based Study.

Body image (BI) can be described as the assessment of both positive and negative emotion for one's own body parts and their characteristics by himself or herself. Current research has concentrated mostly on the status of negative BI as a risk factor for mental health problems rather than as a public health problem, thereby little is known about the effects of BI on quality of life. Thus, the purpose of this study was to assess the BI and Quality of Life (QoL) of individuals and to investigate the relationship between the two. Individuals over 15 living in Isparta city center constitute the universe of this cross-sectional analytical study, carried out in 2014. The BI of individuals was measured by the Body Image Scale and The QoL of individuals was measured using the World Health Organization (WHO) Quality of Life Scale Short Form. The mean age of the participants was 31.9 ± 13.0 and 56.0% were female, 36.8% were married and 81.7% had education above high school. 25.7% had at least one chronic disease and 17.7% received medication regularly. Having good-very good health perception, having higher income than expenses, making regular exercises were predictors in enhancing the quality of life in certain aspects, however having a good body image came out as a predictor enhancing the quality of life in all sub-domains. BI was found closely related with QoL in all sub-domains. Our findings suggest that greater attention should be to be given to BI as a strong predictor of QoL.