Additional file 1 of NF-κB RelA is a cell-intrinsic metabolic checkpoint restricting glycolysis

Additional file 1: Methods

image_5_Association between Sleep-Disordered Breathing during Pregnancy and Maternal and Fetal Outcomes: An Updated Systematic Review and Meta-Analysis.jpeg

Background<p>Due to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern.</p>Methods<p>Pubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot.</p>Results<p>35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC.</p>Conclusion<p>The finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.</p

image_1_Association between Sleep-Disordered Breathing during Pregnancy and Maternal and Fetal Outcomes: An Updated Systematic Review and Meta-Analysis.jpeg

Background<p>Due to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern.</p>Methods<p>Pubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot.</p>Results<p>35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC.</p>Conclusion<p>The finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.</p

image_4_Association between Sleep-Disordered Breathing during Pregnancy and Maternal and Fetal Outcomes: An Updated Systematic Review and Meta-Analysis.jpeg

Background<p>Due to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern.</p>Methods<p>Pubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot.</p>Results<p>35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC.</p>Conclusion<p>The finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.</p

image_2_Association between Sleep-Disordered Breathing during Pregnancy and Maternal and Fetal Outcomes: An Updated Systematic Review and Meta-Analysis.jpeg

Background<p>Due to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern.</p>Methods<p>Pubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot.</p>Results<p>35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC.</p>Conclusion<p>The finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.</p

Reducing Both Pgp Overexpression and Drug Efflux with Anti-Cancer Gold-Paclitaxel Nanoconjugates

<div><p>Repeated administrations of anti-cancer drugs to patients often induce drug resistance. P-glycoprotein (Pgp) facilitates an efficient drug efflux, preventing cellular accumulation of drugs and causing multi-drug resistance (MDR). In this study, we developed a gold-paclitaxel nanoconjugate system to overcome MDR. Gold nanoparticles (GNPs) were conjugated with β-cyclodextrin enclosing paclitaxel (PTX) molecules and PEG molecules. GNP conjugates were effectively endocytosed by both drug-sensitive human lung cancer H460 cells and Pgp-overexpressed drug-resistant H460_PTX cells. Compared with PTX, PGNPs did not induce the Pgp overexpression in drug-sensitive H460 cells after long-term treatment and also avoided being pumped out of cells by overexpressed Pgp molecules in H460_PTX with a 17-fold lower EC₅₀ compared to PTX. Fluorescent microscopy and flow cytometry further confirmed that fluorescent labeled PGNPs (f-PGNPs) maintained a high cellular PTX level in both H460 and H460_PTX cells. These results demonstrated that nano-drug conjugates were able to avoid the development of drug resistance in sensitive cells and evade Pgp-mediated drug resistance and to maintain a high cytotoxicity in drug-resistant cancer cells. These findings exemplify a powerful nanotechnological approach to the long-lasting issue of chemotherapy-induced drug resistance.</p></div

Preparation and characterization of PGNPs.

<p>(A) Preparation of PGNPs. (B, C) TEM images of GNPs and PGNPs. The scale bars are 50 nm. (D) Photographs showing that the PGNPs were well dispersed in water and in cell culture medium with 10% of FBS. The nanoparticles’ hydrodynamic size and zeta potential (ZP) are also shown.</p

Mononostril versus Binostril Endoscopic Transsphenoidal Approach for Pituitary Adenomas: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective.</p><p>Methods</p><p>We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992–2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0.</p><p>Results</p><p>Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p<0.05) than the mononostril group. However, the mononostril group had less rate of epistaxis (0.4% vs. 1.5%, p = 0.008) than the binostril group. For invasive macroadenomas, the binostril group seem to demonstrate a tendency towards better outcomes though there was no subgroup analysis between the two groups.</p><p>Conclusion</p><p>The binostril approach had less temporary diabetes insipidus, anterior pituitary insufficiency, and a shorter length of hospital stay, although they demonstrated a higher rate of epistaxis than the mononstril group. Additionally, the binostril group seemed to suggest a tendency towards better outcomes for invasive macroadenomas.</p></div

Comparison of Cancer Cell Survival Triggered by Microtubule Damage after Turning Dyrk1B Kinase On and Off

Using a tubulin polymerization inhibitor and a tubulin polymerization/Dyrk1B dual inhibitor, we intentionally allowed or blocked the Dyrk1B-coordinated cell survival process in response to microtubule damage. By examining the resulting differential effects on cell function and phenotype, we have elucidated key molecular interactions involved in the Dyrk1B-coordinated cell survival process as well as the associated overall cellular impact. Dyrk1B activation that is induced by microtubule damage triggers microtubule stabilization and promotes the mitochondrial translocation of p21^Cip1/waf1 (referred to as p21 hereafter) to suppress apoptosis. These coordinated survival events rapidly repair microtubules, relieve cell G2/M arrest for 42% of the cells, suppress apoptosis for 27% of the cells, and increase cell viability by 10-fold. That is, the dual inhibitor is 10 times more potent in the inhibition of cancer cell viability. This approach affords a novel drug discovery strategy by targeting both the therapeutic targets and the associated cell survival pathway using a single therapeutic agent

Pgp function determined by intracellular Rhodamine123 (Rh123) accumulation in different cell lines.

<p>Cells were treated with 2.5 μM Rh123 with or without adding Pgp inhibitor. The intracellular accumulation of Rh123 was determined by flow cytometry. Numbers in plots are average fluorescence intensities of intracellular Rh123. The figure is the representative of results from three independent experiments.</p