Oleanolic acid attenuated diabetic mesangial cell injury by activation of autophagy via miRNA-142-5p/PTEN signaling.

Oleanolic acid (OA), a potential drug for diabetic nephropathy (DN) treatment was found to downregulate the expression of microRNA (miR). The research aimed to investigate the effect of OA on autophagy mediated through miR-142-5p targeted PTEN signal. NRK-52E cells were cultured under normal or high glucose condition. DN model were induced by intravenous injection with streptozotocin (55 mg/kg). Renal fibrosis mice were detected by hematoxylin and eosin (HE) staining, Masson staining and immunohistochemistry assay. TargetScan and dual-luciferase reporter assay system was used to detect the target of miR-142-5p. Expression levels of microRNA and proteins were analyzed by real-time PCR and western blotting. Autophagy was decreased in the progression of renal fibrosis in diabetic nephropathy mice (in vivo) and in high glucose-induced NRK-52E cells (rat kidney epithelial cells) (in vitro) as the expression ofLC-3I and LC-3II (indicators of autophagy) were decreased mice MiR-142-5p was unregulated and PTEN was down-regulated in kidney mice and high glucose-induced NRK-52E cells. Targetscan prediction revealed that PTEN was a target of miR-142-5p. OA restricted HG-induced NRK-52E cell fibrosis through inhibition of miR-142-5p to promote PTEN expression and autophagy levels. To sum up, the research indicated that OA promoted autophagy through inhibition of PI3K/AKT/mTOR pathway. OA alleviated diabetic renal fibrosis by increasing autophagy through regulation of miR-142-5p/PTEN via PI3K/AKT/mTOR pathway in NRK-52E cells.

[Finite element analysis of maxillary anterior teeth retraction of posterior teeth with different alveolar bone absorption heights under orthodontic force].

OBJECTIVE: This study applied the direct orthodontic force system to explore the applicability of the finite element method in the simulation of alveolar bone absorption and analyze periodontal stress distribution and the overall displacement trend. METHODS: The horizontal balanced alveolar bones of model 2, 3 and 4 were reduced by 2, 4, and 6 mm by deleting elements in reference to the established height of the normal alveolar bone model 1. Then, stress distribution on the posterior set of teeth and initial total tooth displacement under the simulated load of 1.47 N of orthodontic force were investigated. RESULTS: The total displacement of posterior teeth increased and parodontium Von Mises stress gradually increased as the alveolar bone height decreased. The total displacement trend and parodontium stress drastically increased when alveolar bone absorp-tion reached the height of 4 mm. CONCLUSIONS: When treating patients with alveolar bone loss, stress should be avoided or drasti-cally reduced to prevent irreversible damage to periodontal tissue and to improve the quality of medical treatment.

A resumable two-photon fluorescent probe for Cu2+ and S2- based on magnetic silica core-shell Fe3O4@SiO2 nanoparticles and its application in bioimaging.

A two-photon fluorescent probe for Cu2+ and S2- has been strategically prepared with naphthalimide derivative platform (NPE) covalently grafted onto the surface of magnetic core-shell Fe3O4@SiO2 nanoparticles. The probe (NPE-Fe3O4@SiO2) exhibits selective response to Cu2+ with enhanced fluorescence and efficient separation of Cu2+ with external magnetic field. The consequent product NPE-Fe3O4@SiO2-Cu of NPE-Fe3O4@SiO2 and Cu2+ can work as an excellent sensor for S2- by removing Cu2+ from the complex with fluorescence decreased, recovering the fluorescence of the probe. Therefore, the constituted Off-On-Off type fluorescence monitoring system means the probe is resumable. Moreover, the probe has been used to quantitatively detect Cu2+ and S2- with low detection limits, which are 0.28 µM and 0.12 µM, respectively. Furthermore, the probe shows low cytotoxicity and excellent membrane permeability, which has been successfully applied for monitoring Cu2+ and S2- in living cells and imaging Cu2+ in deep-tissue with two-photon excited fluorescence.

Curcumin Promotes the Clearance of Listeria monocytogenes both In Vitro and In Vivo by Reducing Listeriolysin O Oligomers.

The pore-forming toxin listeriolysin O (LLO), an essential virulence factor that is secreted by Listeria monocytogenes (L. monocytogenes), is responsible for bacterial breaching at the phagosomal membranes and subsequent release into the cytoplasm; it cannot be recognized by the host immune system. The vital role that LLO plays in bacterial pathogenicity and evading host immune clearance makes this virulence a promising target for addressing L. monocytogenes infection. In this study, we hypothesized that curcumin, a polyphenol derived from turmeric that could effectively inhibit LLO pore-forming activity, might be useful in the prevention or treatment of L. monocytogenes infection. Thus, the in vitro protective effects of curcumin against L. monocytogenes infection by targeting LLO were assessed via hemolytic activity assays, cytotoxicity tests, intracellular growth assays, and confocal microscopy. Our results revealed that treating infected macrophages with curcumin can lead to a decrease in LLO-mediated bacteria phagosomal escape and limit the intracellular growth of L. monocytogenes. Moreover, results from animal experiments show that this natural compound effectively increases protection against bacterial infection and helps the host to clear the invading pathogen completely from an animal model, establishing it as a potent antagonist of L. monocytogenes. The results from our molecular modeling and mutational analysis demonstrated that curcumin directly engages with domains 2 and 4 of LLO, thereby decreasing the hemolytic activity of LLO by influencing its oligomerization. Taken together, these results suggest that, as an antitoxin agent, curcumin can be further developed into a novel therapy against L. monocytogenes infections by targeting LLO.

A coumarin-based two-photon probe for hydrogen peroxide.

A new fluorescence probe was developed for hydrogen peroxide (H2O2) detection based on donor-excited photo induced electron transfer (D-PET) mechanism, together with the benzil as a quenching and recognizing moiety. The benzil could convert to benzoic anhydride via a Baeyer-Villiger type reaction in the presence of H2O2, followed by hydrolysis of benzoicanhydride to give benzoic acid, and the fluorophore released. The probe was synthesized by a 6-step procedure starting from 4-(diethylamino)salicylaldehyde. A density functional theory (DFT) calculation was performed to demonstrate that the benzil was a fluorescence quencher. The probe was evaluated in both one-photon and two-photon mode, and it exhibited high selectivity toward H2O2 over other reactive oxygen species and high sensitivity with a detection limit of 0.09 µM. Furthermore, the probe was successfully applied to cell imaging of intracellular H2O2 levels with one-photon microscopy and two-photon microscopy. The superior properties of the probe made it of great potential use in more chemical and biological researches.

Allicin-induced global gene expression profile of Saccharomyces cerevisiae.

To understand the response mechanisms of fungus cells upon exposure to the natural fungicide allicin, we performed commercial oligonucleotide microarrays to determine the overall transcriptional response of allicin-treated Saccharomyces cerevisiae strain L1190. Compared with the transcriptional profiles of untreated cultures, 147 genes were significantly upregulated, and 145 genes were significantly downregulated in the allicin-treated cells. We interpreted the microarray data with the hierarchical clustering tool, T-profiler. Major transcriptional responses were induced by allicin and included the following: first, Rpn4p-mediated responses involved in proteasome gene expression; second, the Rsc1p-mediated response involved in iron ion transporter activity; third, the Gcn4p-mediated response, also known as general amino acid control; finally, the Yap1p-, Msn2/4p-, Crz1p-, and Cin5p-mediated multiple stress response. Interestingly, allicin treatment, similar to mycotoxin patulin and artificial fungicide thiuram treatment, was found to induce genes involved in sulfur amino acid metabolism and the defense system for oxidative stress, especially DNA repair, which suggests a potential mutagenicity for allicin. Quantitative real-time reverse transcription-polymerase chain reaction was performed for selected genes to verify the microarray results. To our knowledge, this is the first report of the global transcriptional profiling of allicin-treated S. cerevisiae by microarray.

[Expression of vascular endothelial growth factor A and C in human breast cancer and their significance].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) family is related to angiogenesis. VEGF-A and VEGF-C are closely related to tumorigenesis and lymphatic metastasis. This study was to detect the expression of VEGF-A and VEGF-C in breast cancer, and explore their correlation to cell proliferation, microvessel density (MVD), and lymphatic metastasis of breast cancer. METHODS: The expression of VEGF-A, VEGF-C, proliferating cell nuclear antigen (PCNA), and CD34 in 98 samples of breast cancer were detected by SP immunohistochemistry. RESULTS: The positive rate of VEGF-A was 85.7%; that of VEGF-C was 90.8%. The positive rates of VEGF-A and VEGF-C were significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis (P<0.05). The positive rate of PCNA was 98.0%; its expression level was increased with the expression levels of VEGF-A and VEGF-C (r=0.432, P=0.000; r=0.294, P=0.001). MVD was significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis(64.26+/-26.40 vs. 50.29+/-29.35, P<0.05). MVD was positively correlated to the expression of VEGF-A (r=0.327, P<0.001), but had no correlation to VEGF-C (r=0.123, P>0.05). CONCLUSIONS: VEGF-A mainly mediates angiogenesis, cell proliferation, and metastasis of human breast cancer. VEGF-C promotes cell proliferation of human breast cancer; it is correlated to lymph node metastasis, but has no correlation to MVD.