Neurocytoprotective Effects of Aliphatic Hydroxamates from Lovastatin, a Secondary Metabolite from <i>Monascus</i>-Fermented Red Mold Rice, in 6‑Hydroxydopamine (6-OHDA)-Treated Nerve Growth Factor (NGF)-Differentiated PC12 Cells

Lovastatin, a secondary metabolite isolated from <i>Monascus</i>-fermented red rice mold, has neuroprotective activity and permeates the blood–brain barrier. The aim of this study was to enhance the activity of lovastatin for potential use as a treatment for neuronal degeneration in Parkinson’s disease. Six lovastatin-derived compounds were semisynthesized and screened for neurocytoprotective activity against 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma PC12 cells. Four compounds, designated as <b>3a</b>, <b>3d</b>, <b>3e</b>, and <b>3f</b>, significantly enhanced cell viability. In particular, compound <b>3f</b> showed excellent neurocytoprotective activity (97.0 ± 2.7%). Annexin V-FITC and propidium iodide double staining and 4′,6-diamidino-2-phenylindole staining indicated that compound <b>3f</b> reduced 6-OHDA-induced apoptosis in PC12 cells. Compound <b>3f</b> also reduced caspase-3, -8, and -9 activities, and intracellular calcium concentrations elevated by 6-OHDA in a concentration-dependent manner, without inhibiting reactive oxygen species generation. JC-1 staining indicated that compound <b>3f</b> also stabilized mitochondrial membrane potential. Thus, compound <b>3f</b> may be used as a neurocytoprotective agent. Future studies should investigate its potential application as a treatment for Parkinson’s disease

Liquid crystalline non-linear S-shaped oligomers consisting of azobenzene and biphenylene units: synthesis, characterisation and influence of central spacer

<p>A series of non-linear S-shaped liquid crystal oligomers wherein the molecule consists of biphenylene moiety as a central core unit and two symmetrical side arms azobenzene moieties joined to catechol as a linkage group have been successfully synthesised and characterised. The members in this series possess different inner spacer with carbon number n ranging from 4 to 9 while the outer spacer length located in azobenzene moieties are remains unaltered. The members with even parity exhibit monotropic phase, whereas homologues with odd parity display enantiotropic phase. The appearance of nematic, smectic A and smectic B phases was validated with texture observation under polarised light and X-ray diffraction (XRD). The XRD study on the S-shaped oligomer indicates that the arrangement of smectic phase exists as an intercalated structure. The S-shaped oligomer shows photoisomerisation properties in solution whereby the <i>trans</i> to <i>cis</i> isomerisation for this molecule is accomplished 1140 s, whereas reverse process under thermal back reaction occurred in 4620 min.</p

Exploration of Energy Modulations in Novel RhB-TPE-Based Bichromophoric Materials via Interactions of Cu²⁺ Ion under Various Semiaqueous and Micellar Conditions

Novel bichromophoric materials <b>TR-A</b> and <b>TR-B</b> consisting of an entirely new combination of TPE and RhB units were developed to explore the optimum conditions of energy modulations via pH variation and Cu²⁺ interaction at various water contents of CH₃CN. Interestingly, <b>TR-A</b> and <b>TR-B</b>, at 60 and 70% water contents, respectively, favored the optimum Cu²⁺-mediated energy modulations from TPE to RhB and thus achieve the brightest orange emissions of free RhB with complete disappearance of aggregation-induced emission (AIE) from TPE. Furthermore, various micellar conditions of triton-X-100, SDS, and CTAB were employed to adjust energy modulations of <b>TR-A</b> and <b>TR-B</b> at high water contents (at 80 and 90%, respectively). The incorporation of RhB into triton-X-100 micellar cavities disrupted AIE from TPE; thus, none of the energy modulations from TPE to RhB occurred even in the presence of Cu²⁺ ion. Interestingly, the micellar conditions of anionic surfactant (SDS) favored the increased local concentration of Cu²⁺ ions in the vicinity of scavangable RhB and facilitated the generation of noncyclic free RhB in situ via bright-orange emissions

Characteristics and clinical outcomes of head-injured cyclists with and without helmets in urban and rural areas of Taiwan: A 15-year study

<p><b>Objective</b>: Bicycle riding is increasingly popular in Taiwan, but the number of cyclists injured and cyclists' death rates are both increasing. The aim of this study was to investigate the different characteristics and clinical outcomes of traffic accident–related head injuries among cyclists in urban and rural areas.</p> <p><b>Methods</b>: Records of 812 patients (533 urban and 279 rural) admitted to 27 hospitals in Taipei City and Hualien County as the result of a traumatic head injury while bicycling between 1998 and 2013 were retrieved for study. Demographics, details about the accident, protective helmet use, and clinical outcomes were then subjected to analysis.</p> <p><b>Results</b>: Urban victims were more likely to be injured during morning and early evening rush hours and rural victims during the day; most urban victims were between 19 and 34 years of age and injured in the slow lane; rural victims tended to be younger or older and were injured in the fast lane (all <i>P</i> ≤.001). Riders who wore a helmet were less likely to suffer loss of consciousness (odds ratio [OR] = 0.31), amnesia (OR = 0.069), neurological disorders (OR = 0.205), or facial fractures (OR = 0.369). Older age, more severe head injuries, and bicycle–motor vehicle collisions influenced the severity of symptoms on admission and the residual effects at discharge.</p> <p><b>Conclusions</b>: Differences in the characteristics of injuries in urban and rural areas and the utilization of protective helmets may help government authorities adopt appropriate policies to promote safer and more enjoyable cycling.</p

JARID1B downregulation results in the decrease of cell invasion capability.

<p>(A) Western blots confirmed JARID1B expression was suppressed in the two shRNA clones 1 and 2 as compared to the control, and there was correlative down-regulation of Nestin and BCL-xL, while BAX was up-regulated. (B) Wound healing migration assay of SK-N-BE(2) cells show that JARID1B-shRNA infected cells were less motile than control wild type cells (C) Matrigel invasion assay and histogram representation show that JARID1B knockdown induced very significant downregulation of the invasive potential of the SK-N-BE(2) cells (**, p<0.01).</p

Evaluation of JARID1B expression and stemness functions in <i>MYCN</i> and <i>non-MYCN</i> neuroblastoma (NB) cell lines.

<p>(A) Western blot analysis was performed to investigate the expression of JARID1B and α-MYCN in <i>MYCN</i> amplification (MNA⁺) and <i>non-MYCN</i> amplification (MNA^-) NB cells. (B) The SP percentage was analyzed in MNA⁺ and MNA^- NB cells by Hoechst staining and flow cytometry. SK-N-BE(2) and SK-N-AS cells had 9.05% and 1.45% SP cells (C) Representative Aldeflour assay result of MNA⁺ SK-N-BE(2) and MNA^- SK-N-AS NB cells showed 17.2% and 3.43% ALDH+ subpopulation, respectively. Data was collected from three independent experiments.</p

JARID1B-silencing suppresses tumorsphere formation and increases cisplatin sensitivity.

<p>(A) Tumorspheres generated from wild type and JARID1B-shRNA 1- and 2- infected SK-N-BE(2) cells. (B and C) JARID1B knockdown caused significant reduction in number and sizes of tumorspheres formed. (D) Cell viability assay show that the cytotoxicity effect of cisplatin was significantly enhanced by JARID1B silencing. All assays were repeated at least three times. * and ** indicate p<0.05 and p<0.001.</p

Silencing JARID1B downregulates Jagged/Notch signaling transduction pathway.

<p>The expression of Notch and its ligand in wild type and JARID1B-silenced SK-N-BE(2) cells were analyzed by Western blot assay. (A) JARID1B-silencing disrupted Jagged1, Notch1 and Notch 2 signaling. (B) Comparative bar diagrams demonstrate the downregulation of Notch signaling in the wild type SK-N-BE(2) cells, compared to the JARID1B-silenced SK-N-BE(2) cells. The intensity was measured relative to loading control (β-actin) from three independent experiments. *, p<0.05 (C) Immunofluorescent staining showing that JARID1B-silencing downregulated the expression of Notch1. Notch1 (green) colocalizes with JARID1B (red) in the nucleus (DAPI for nuclear staining, blue).</p

Neuroblastoma SP cells with higher JARID1B expression are more resistant to chemotherapeutics.

<p>(A) The morphology of SK-N-BE(2), SK-N-DZ, SK-N-AS and SK-N-SH spheroid. (B) Comparative analysis of JARID1B expression in SK-N-BE(2) and SK-N-AS cells, as well as the tumorsphere derived from either cells, SK-N-BE(2)-S and SK-N-AS-S show that the tumorspheres were more enriched in JARID1B and Nestin protein. (C) Immunofluorescence analysis shows SK-N-BE(2) and SK-N-AS tumorspheres expressing JARID1B (red) and Nestin (green) and nucleus marker, DAPI, blue. (D) SRB assay showing that the tumorspheres SK-N-BE (2)-S were more resistant to chemotherapeutics than the parental SK-N-BE (2) cells. Error bars represent the SD from three independent experiments. ** p < 0.01.</p

Silencing JARID1B decreases epithelial to mesenchymal transition (EMT).

<p>(A) Western blot analysis of epithelial and mesenchymal markers’ expression in wild type and JARID1B-silenced SK-N-BE(2) cells show downregulation of N-cadherin and vimentin in response to JARID1B knockdown, while E-cadherin was upregulated. β-actin served as loading control. (B) Bar chart quantification of (A). Expression of EMT markers are normalized against β-actin. Assay was performed three times. *, represent p<0.05.</p