METHODS: Cellular assays tested six different concentrations (up to 5%) of the PE for cell viability levels and reactive oxygen species (ROS) levels of human immortalised epidermal cells (HaCaTs). The identified non-cytotoxic concentration (0.5% PE) was then tested by gene assays. A commercial foundation containing 0.5% PE (PEF0.5) was tested for safety, skin protective effectiveness, and user satisfaction.
RESULTS: Compared to the control groups, 0.5% PE had a significant inhibitory effect on the expression level of MMP-1 but promoted the expression of COL1A1, COL3A1, ELN, and AQP3. PEF0.5 significantly (p 0.05) differences were detected in the foundation's effectiveness and usability.
CONCLUSION: Applying PEF0.5 for 28 days may improve the skin barrier function, as indicated by skin TEWL, hydration, wrinkle, elasticity, and sebum content, without any adverse effects.
METHODS AND RESULTS: Cur-NPs (30 nm and 200 nm) were nebulized separately onto the multidrug-resistant lung cancer cells (H69AR). Smaller NPs induced significantly higher cell death owing to a higher rate of particle internalization via dynamin-dependent clathrin-mediated endocytosis. Owing to the higher lysosome trafficking of Cur-NP30 nm compared to Cur-NP200 nm, oxidation of lysosome was higher (0.47 ± 0.08 vs 0.38 ± 0.08), contributing to significantly higher mitochondrial membrane potential loss (1.57 ± 0.17 vs 1.30 ± 0.11). MRP1 level in H69AR cells was reduced from 352 ± 12.3 ng/µg of protein (untreated cells) to 287 ± 12 ng/µg of protein (Cur-NP30 nm) and 303 ± 13.4 ng/µg of protein (Cur-NP200 nm). NF-κB, and various cytokine expressions were reduced after treatment with nebulized Cur-NPs.
CONCLUSIONS: Nebulized Cur-NPs formulations could be internalized into the H69AR cells. The Cur-NPs toxicity toward the H69AR was size and time-dependent. Cur-NP30 nm was more effective than Cur-NP200 nm to retain within the cells to exert higher oxidative stresss-induced cell death.
Methods: Human neuroblastoma cells SH-SY5Y (as a neuronal model) and human glioblastoma cells T98G (as an astrocytic model), were treated with 100-500 µM PA, oleic acid (OA) or lauric acid (LA) for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ), a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS) level was determined using 2',7'-dichlorofluorescien diacetate (DCFH-DA) assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS) assay.
Results: MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA's neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity-suggesting a mechanism of PA-induced leptin resistance. Annexin V/PI flow cytometry analysis revealed PA-induced increase in percentages of cells in annexin V-positive/PI-negative quadrant (early apoptosis) and subG0-G1 fraction, accompanied by a decrease in G2-M phase cells. The PA-induced ROS production and lipid peroxidation was at greater extent in T98G as compared to that in SH-SY5Y.
Discussion: In conclusion, PA induces apoptosis by increasing oxidative stress in neurons and astrocytes. Taken together, the results suggest that HFD may cause neuronal and astrocytic damage, which indirectly proposes that CNS pathologies involving neuroinflammation and reactive gliosis could be prevented via the diet regimen.
OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.
MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis.
RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures.
CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.