Effects of shift work on sleep quality and cardiovascular function in Taiwanese police officers.

This study aimed to investigate the effects of shift work on sleep quality, cardiovascular function, and physical activity (PA) levels in Taiwanese police officers. Twenty-one male police officers aged 26.9 ± 4.1 years old located in Taipei voluntarily participated in this study. The participants completed the resting heart rate (HR) and hemodynamic variables (e.g. blood pressure, BP) before and after day-time (DTW) and night-time (NTW) shift work phases (5 working days and 2 resting days for each phase). Additionally, an actigraphy was administered to measure PA and sleep patterns in the last 3 working days. The average total sleep time and sleep efficiency were 278.5 ± 79. 6 min and 72.9 ± 10%, respectively, in the NTW phases, which were significantly lower than that in the DTW phases. A comparison of the PA characteristics between the two phases revealed that a lower proportion of moderate-vigorous PA (1.2 ± 0.8%) and a greater proportion of sedentary behaviour PA (74.8 ± 6.4%) was found in the NTW phases. The results of hemodynamic measures demonstrated that the police officers have significantly elevated systolic BP by 3.3% and diastolic BP by 3.9% after the NTW phases. Furthermore, the NTW phases exhibited a significantly higher percentage change ratio of systolic BP and diastolic BP compared to the DTW phases. Compared with the DTW phases, the NTW phase was significantly more likely to report higher decreasing parasympathetic-related HR variability with a range of -5.9% to -7.8%. In conclusion, night-time shift work resulted in negative physiological changes leading to adverse effects on the health and well-being of Taiwanese police officers.

Isolation and Structure Elucidation of Cembranoids from a Dongsha Atoll Soft Coral Sarcophyton stellatum.

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A⁻C (1⁻3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7⁻16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells.

Bioactive Steroids from the Formosan Soft Coral Umbellulifera petasites.

Three new steroids, petasitosterones A and B (1 and 2) and a spirosteroid petasitosterone C (3), along with eight known steroids (4-11), were isolated from a Formosan marine soft coral Umbellulifera petasites. The structures of these compounds were elucidated by extensive spectroscopic analysis and comparison of spectroscopic data with those reported. Compound 3 is a marine steroid with a rarely found A/B spiro[4,5]decane ring system. Compounds 1-3 and 5 displayed inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas 2 and 5 exhibited significant anti-inflammatory activity to inhibit nitric oxide (NO) production. The inhibitory activities for superoxide anion generation and elastase release of compounds 1-11 were also examined to evaluate the anti-inflammatory potential, and 2-4 were shown to exhibit significant activities.

Involvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines.

BACKGROUND: The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile. METHODS: Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 µm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array. RESULTS: DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5' region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion. CONCLUSIONS: DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation.

Bioactive Isoprenoid-Derived Natural Products from a Dongsha Atoll Soft Coral Sinularia erecta.

Four new isoprenoids, including two norcembranoids sinulerectols A and B (1 and 2), a cembranoid sinulerectol C (3), and a degraded cembranoid sinulerectadione (4), along with three known isoprenoids, an unnamed norcembrene (5), sinularectin (6), and ineleganolide (7), and a known nitrogen-containing compound (Z)-N-[2-(4-hydroxyphenyl)ethyl]-3-methyldodec-2-enamide (8), were isolated from an extract of the marine soft coral Sinularia erecta. The structure of sinularectin (6) was revised, too. Compounds 3, 4, and 8 exhibited inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas 1, 2, and 8 displayed potent anti-inflammatory activity in fMLP/CB-stimulated human neutrophils.

Oxygenated eremophilane- and neolemnane-derived sesquiterpenoids from the soft coral Lemnalia philippinensis.

Five sesquiterpene-related metabolites (1-5), including two new eremophilane-type compounds, philippinlins C and D (1 and 2) and a 4,5-seconeolemnane philippinlin E (3), were isolated from the organic extract of a Taiwanese soft coral Lemnalia philippinensis. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis and by comparison of NMR data with those of related metabolites. Compound 3 was suggested to be derived from the neolemnane skeleton.

Numerosol A-D, new cembranoid diterpenes from the soft coral Sinularia numerosa.

Four new cembrane-type diterpenes; numerosol A-D (1-4); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED50 of 6.9 µM.

Tortuosenes A and B, new diterpenoid metabolites from the Formosan soft coral Sarcophyton tortuosum.

Tortuosenes A and B (1 and 2), possessing new diterpenoid molecular structures, were isolated from the Formosan soft coral Sarcophyton tortuosum along with a known cembrane, emblide (3). The structures of 1 and 2 were established by extensive spectroscopic analysis, and the absolute configuration of 1 was determined by TDDFT ECD calculations. Tortuosene A was found to display significant inhibitory effects on the generation of the superoxide anion in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced neutrophils.

Oxygenated ylangene-derived sesquiterpenoids from the soft coral Lemnalia philippinensis.

Chemical examination of a Taiwanese soft coral Lemnalia philippinensis led to the isolation of three oxygenated ylangene-derived sesquiterpenoids 1-3, including two new metabolites, philippinlins A and B (1 and 2). The structures of these compounds were elucidated on the basis of detailed spectroscopic data. Compound 1 was shown to exhibit cytotoxicity against HepG2, MDA-MB231 and A549 cancer cell lines.

Secosteroids and norcembranoids from the soft coral Sinularia nanolobata.

Two new 9,11-secosteroids, 22α-acetoxy-24-methylene-3ß,6α,11-trihydroxy-9, 11-seco-cholest-7-en-9-one (1) and 11-acetoxy-24-methylene-1ß,3ß,6α-trihydroxy-9, 11-seco-cholest-7-en-9-one (2), as well as two known norcembranoids, 5-epi-sinuleptolide (3) and sinuleptolide (4), were isolated from the soft coral Sinularia nanolobata. The structures of these metabolites were elucidated on the basis of extensive spectroscopic analysis. The anti-HCMV (human cytomegalovirus) activity of 1-4 and its cytotoxicity against selected cell lines were evaluated.

Parathyrsoidins A-D, four new sesquiterpenoids from the soft coral Paralemnalia thyrsoides.

Four new nardosinane-type sesquiterpenoids, parathyrsoidins A-D (1-4) were isolated from the soft coral Paralemnalia thyrsoides. The structures of parathyrsoidins A-D (1-4) were determined by extensive spectral analysis and their cytotoxicity against selected cancer cell lines as well as antiviral activity against human cytomegalovirus (HCMV) were evaluated in vitro.

Targeting the EGFR/PCNA signaling suppresses tumor growth of triple-negative breast cancer cells with cell-penetrating PCNA peptides.

Tyrosine 211 (Y211) phosphorylation of proliferation cell nuclear antigen (PCNA) coincides with pronounced cancer cell proliferation and correlates with poor survival of breast cancer patients. In epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant cells, both nuclear EGFR (nEGFR) expression and PCNA Y211 phosphorylation are increased. Moreover, the resistance to EGFR TKI is a major clinical problem in treating EGFR-overexpressing triple-negative breast cancer (TNBC). Thus, effective treatment to combat resistance is urgently needed. Here, we show that treatment of cell-penetrating PCNA peptide (CPPP) inhibits growth and induces apoptosis of human TNBC cells. The Y211F CPPP specifically targets EGFR and competes directly for PCNA tyrosine Y211 phosphorylation and prevents nEGFR from binding PCNA in vivo; it also suppresses tumor growth by sensitizing EGFR TKI resistant cells, which have enhanced nEGFR function and abrogated classical EGFR membrane signaling. Furthermore, we identify an active motif of CPPP, RFLNFF (RF6 CPPP), which is necessary and sufficient to inhibit TKI-resistant TNBC cell growth of orthotopic implanted tumor in mice. Finally, the activity of its synthetic retro-inverted derivative, D-RF6 CPPP, on an equimolar basis, is more potent than RF6 CPPP. Our study reveals a drug candidate with translational potential for the future development of safe and effective therapeutic for EGFR TKI resistance in TNBC.

Smurf2-mediated degradation of EZH2 enhances neuron differentiation and improves functional recovery after ischaemic stroke.

EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. Previously, we showed that EZH2 downregulation enhances neuron differentiation of human mesenchymal stem cells (hMSCs); however, the underlying mechanisms of EZH2-regulated neuron differentiation are still unclear. Here, we identify Smurf2 as the E3 ubiquitin ligase responsible for the polyubiquitination and proteasome-mediated degradation of EZH2, which is required for neuron differentiation. A ChIP-on-chip screen combined with gene microarray analysis revealed that PPARγ was the only gene involved in neuron differentiation with significant changes in both its modification and expression status during differentiation. Moreover, knocking down PPARγ prevented cells from undergoing efficient neuron differentiation. In animal model, rats implanted with intracerebral EZH2-knocked-down hMSCs or hMSCs plus treatment with PPARγ agonist (rosiglitazone) showed better improvement than those without EZH2 knockdown or rosiglitazone treatment after a stroke. Together, our results support Smurf2 as a regulator of EZH2 turnover to facilitate PPARγ expression, which is specifically required for neuron differentiation, providing a molecular mechanism for clinical applications in the neurodegenerative diseases.

Lochmolins A-G, new sesquiterpenoids from the soft coral Sinularia lochmodes.

Seven new sesquiterpenoids, lochmolins A-G (1-7), were isolated from a Taiwanese soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic study. Compounds 1-4 were found to inhibit the accumulation of the LPS-induced pro-inflammatory COX-2 protein in RAW264.7 macrophage cells.

Nuclear EGFR suppresses ribonuclease activity of polynucleotide phosphorylase through DNAPK-mediated phosphorylation at serine 776.

Nuclear existence of epidermal growth factor receptor (EGFR) has been documented for more than two decades. Resistance of cancer to radiotherapy is frequently correlated with elevated EGFR expression, activity, and nuclear translocation. However, the role of nuclear EGFR (nEGFR) in radioresistance of cancers remains elusive. In the current study, we identified a novel nEGFR-associated protein, polynucleotide phosphorylase (PNPase), which possesses 3' to 5' exoribonuclease activity toward c-MYC mRNA. Knockdown of PNPase increased radioresistance. Inactivation or knock-down of EGFR enhanced PNPase-mediated c-MYC mRNA degradation in breast cancer cells, and also increased its radiosensitivity. Interestingly, the association of nEGFR with PNPase and DNA-dependent protein kinase (DNAPK) increased significantly in breast cancer cells after exposure to ionizing radiation (IR). We also demonstrated that DNAPK phosphorylates PNPase at Ser-776, which is critical for its ribonuclease activity. The phospho-mimetic S776D mutant of PNPase impaired its ribonuclease activity whereas the nonphosphorylatable S776A mutant effectively degraded c-MYC mRNA. Here, we uncovered a novel role of nEGFR in radioresistance, and that is, upon ionizing radiation, nEGFR inactivates the ribonuclease activity of PNPase toward c-MYC mRNA through DNAPK-mediated Ser-776 phosphorylation, leading to increase of c-MYC mRNA, which contributes to radioresistance of cancer cells.

Nanolobatolide, a new C18 metabolite from the Formosan soft coral Sinularia nanolobata.

Nanolobatolide (1), possessing a novel C(18) molecular structure, was isolated from the Formosan soft coral Sinularia nanolobata. The structure of 1 was established by extensive spectroscopic study and confirmed by X-ray diffraction analysis. A plausible biosynthetic pathway of 1 was proposed. Nanolobatolide (1) has been found to possess significant anti-neuroinflammatory and neuroprotective activities.

9,11-Secosterols from the soft corals Sinularia lochmodes and Sinularia leptoclados.

Chemical investigations on the EtOAc-soluble fractions from the EtOH extract of two Formosan soft corals afforded two new 9,11-secosteroids, 3beta,11-dihydroxy-5beta,6beta-epoxy-24-methylene-9,11-secocholestan-9-one (1) and 3beta,11-dihydroxy-24-methylene-9,11-secocholestan-9-one (2), from Sinularia lochmodes and Sinularia leptoclados, respectively, along with two known analogues (3 and 4) from S. leptoclados. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those of the known compound 3. The cytotoxicity of 2-4 toward a limited panel of cancer cell lines is also reported.

Sinulochmodins A-C, three novel terpenoids from the soft coral Sinularia lochmodes.

An unprecedented C,C-linked dimeric norcembranoid (sinulochmodin A, 1), a novel isocembranoid (sinulochmodin B, 2), and a novel yonarane norditerpenoid (sinulochmodin C, 3) were isolated from the soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic analysis and on the basis of the absolute structures of two related norditerpenoids (4 and 5), which were determined for the first time by a modified Mosher method. A plausible pathway for the biosynthesis of 1 and 3-5 from 2 was postulated. [structure: see text]