Conclusion PGC-1α protects neuronal cells against MPP+-induced toxicity partially through the acetylation of PGC-1α mediated by GCN5, and mostly through the phosphorylation PGC-1α mediated by p38MAPK or AMPK. Therapeutic reagents activating PGC-1α may be valuable for preventing mitochondrial dysfunction in PD by against oxidative damage. Methods With established the 1-methyl-4-phenylpyridinium (MPP+)-induced cell model of PD, the effects of MPP+ and experimental reagents on the cell viability was investigated. The expression of PGC-1α, general control of nucleotide synthesis 5 (GCN5), p38 mitogen-activated protein kinase (p38MAPK) and adenosine monophosphate activated protein kinase (AMPK) were detected by Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry. All statistical analyses were carried out using one-way ANOVA.Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence, distant metastasis and drug-resistance, in the vast majority of cancer patients.  https://www.selleckchem.com/products/ldn193189.html  Therefore, there is an urgent need to identify new drugs that can target and eradicate CSCs. To identify new molecular targets that are unique to CSCs, we previously compared MCF7 2D-monolayers with 3D-mammospheres, which are enriched in CSCs. We observed that 25 mitochondrial-related proteins were >100-fold over-expressed in 3D-mammospheres. Here, we used these 25 proteins to derive short gene signatures to predict distant metastasis (in N=1,395 patients) and tumor recurrence (in N=3,082 patients), by employing a large collection of transcriptional profiling data from ER(+) breast cancer patients. This analysis resulted in a 4-gene signature for predicting distant metastasis, with a hazard ratio of 1.91-fold (P=2.2e-08). This provides clinical evidence to support a role for CSC mitochondria in metastatic dissemination. Next, we employed a panel oion diagnostics to assess which patients may benefit most from anti-mito-ribosome therapy. Overall, our studies provide the necessary proof-of-concept, and in vivo functional evidence, that mitochondrial inhibitors can successfully and selectively target the biological process of cancer cell metastasis. Ultimately, we envision that mitochondrial inhibitors could be employed to develop new treatment protocols, for clinically providing metastasis prophylaxis, to help prevent poor clinical outcomes in cancer patients.Cryptocarya species are mainly distributed in Africa, Asia, Australia and South America, widely used in traditional medicines for the treatment of skin infections and diarrhea. The present investigation reports on the extraction by hydrodistillation and the chemical composition of three Cryptocarya species (Cryptocarya impressa, Cryptocarya infectoria, and Cryptocarya rugulosa) essential oils from Malaysia. The chemical composition of these essential oils was fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). A total of 51 components were identified in C. impressa, C. infectoria, and C. rugulosa essential oils representing 91.6, 91.4, and 83.0% of the total oil, respectively. The high percentages of α-cadinol (40.7%) and 1,10-di-epi-cubenol (13.4%) were found in C. impressa oil. β-Caryophyllene (25.4%) and bicyclogermacrene (15.2%) were predominate in C. infectoria oil. While in C. rugulosa oil, bicyclogermacrene (15.6%), δ-cadinene (13.8%), and α-copaene (12.3%) were predominate. To the best of our knowledge, there is no report on the essential oil composition of these three species.Caveolae are defined as 50-100 nm wide pits in the plasma membrane containing oligomeric caveolin proteins. They have been implicated in endocytosis (including phagocytosis), transcytosis, calcium signalling, and numerous other signal transduction events. Caveolin-1, a major structural component of caveolae, enhances Rab5 activity. In this study, we examined the effect of a synthetic cell-permeable peptide of the caveolin-1 scaffolding domain (CSD) on phagocytosis. Treatment with the CSD peptide increased Rab5 activity, Rab5-early endosome antigen 1 (EEA1) interaction, and phagocytosis of Escherichia coli. The results suggest that the synthetic cell-permeable CSD peptide is an activator of phagocytosis.Objective The present study aimed to evaluate cytotoxic, apoptotic, and anti-inflammatory properties of bee venom (BV) as well as changes in cytokine secretion levels and nitric oxide (NO) production using three different cancer cell lines [liver (Hep-G2), breast (MCF-7), and cervical (HPV-18 infected HeLa cells)] and two normal cells (splenocytes and macrophages (MQ). Methods Cytotoxic activity of BV against tumor cell lines and normal splenocytes/MQ was tested by MTT assay. By ELISA (ELISA); Tumor necrosis factor (TNF-α), Interleukine (IL-10) and interferon (IFN-γ) were measured. Caspase three expressions was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). Nitric oxide (NO) was estimated using a colorimetric assay. Results BV has a significant cytotoxic effect on all cell lines in a dose- and time-dependent manner; none of them was toxic for normal cells. Treating Hep-G2 cells with BV showed a reduction in IL-10, elevation in TNF-α with no change in IFN-γ level. MCF-7 cells have low IL-10 and TNF-α and high IFN-γ production level. Elevation of IL-10 and IFN-γ coincides with a reduction in TNF-α level was demonstrated in HeLa cells. The expression of Caspase three was dramatically increased with elevation in BV concentration in all tested cancer cell lines. A gradual decrease in NO production by MQ with increasing BV dose was observed. Conclusion Taken together, our results stressed on the importance of BV as a potent anti-tumor agent against various types of cancers (Liver, Breast, and Cervix). Further steps towards the use of BV for pharmacological purposes must be done.To develop implants with improved bone ingrowth, titanium substrates were coated with homogeneous and dense struvite (MgNH4PO4·6H2O) layers by means of electrochemically assisted deposition. Strontium nitrate was added to the coating electrolyte in various concentrations, in order to fabricate Sr-doped struvite coatings with Sr loading ranging from 10.6 to 115 μg/cm2. It was expected and observed that osteoclast activity surrounding the implant was inhibited. The cytocompatibility of the coatings and the effect of Sr-ions in different concentrations on osteoclast formation were analyzed in vitro. Osteoclast differentiation was elucidated on morphological, biochemical as well as on gene expression level. It could be shown that moderate concentrations of Sr2+ had an inhibitory effect on osteoclast formation, while the growth of osteoblastic cells was not negatively influenced compared to pure struvite surfaces. In summary, the electrochemically deposited Sr-doped struvite coatings are a promising approach to improve bone implant ingrowth.