Additional file 4. of CircRNAs as biomarkers of cancer: a meta-analysis

Figure S3. Forest plots of PLR, NLR, DOR, AUC, and funnel plot for diagnosis of circRNA in tumors among 17 studies, which excluded 2 studies because of relatively small sample size (less than 50). (A) Sensitivity; (B) Specificity; (C) PLR; (D) NLR; (E) DOR; (F) AUC; and (G) Funnel plot. (TIFF 1858 kb

Additional file1. of CircRNAs as biomarkers of cancer: a meta-analysis

Table S1 All characteristics of all studies on the use of circRNAs as diagnostic biomarkers of cancer. (DOCX 100 kb

Additional file 2. of CircRNAs as biomarkers of cancer: a meta-analysis

Figure S1. QUADAS studies of diagnostic test accuracy. (TIFF 1823 kb

Additional file 3. of CircRNAs as biomarkers of cancer: a meta-analysis

Figure S2. Forest plots of sensitivity, specificity, PLR, NLR, DOR, AUC, and funnel plot for diagnosis of circRNA in tumors among 18 studies, which excluded different endogenous reference study. (A) Sensitivity; (B) Specificity; (C) PLR; (D) NLR; (E) DOR; (F) AUC; and (G) Funnel plot. (TIFF 1925 kb

Switching of the Triplet Excited State of Rhodamine/Naphthaleneimide Dyads: An Experimental and Theoretical Study

Rhodamine–bromonaphthaleneimide (<b>RB–NI</b>) and rhodamine–bromonaphthalenediimide (<b>RB–NDI</b>) dyads were prepared for switching of the <i>triplet</i> excited states. Bromo-NI or bromo-NDI parts in the dyads are the spin converters, i.e., the triplet state producing modules, whereas the RB unit is the acid-activatable electron donor/energy acceptor. NI and NDI absorb at 359 and 541 nm, and the T₁ state energy levels are 2.25 and 1.64 eV, respectively. RB undertakes the reversible spirolactam (RB-c) ↔ opened amide (RB-o) transformation. RB-c shows no visible light absorption, and the triplet-state energy level is <i>E</i>_T1 = 3.36 eV. Conversely RB-o shows strong absorption at 557 nm, and <i>E</i>_T1 is 1.73 eV. Thus, the acid-activated fluorescence-resonance-energy-transfer (FRET) competes with the ISC of NI or NDI. No triplet state was observed for the dyads with nanosecond time-resolved transient absorption spectroscopy. Upon addition of acid, strong fluorescence and long-living triplet excited states were observed. Thus, the producing of triplet state is acid-activatable. The triplet state of <b>RB–NI</b> is <i>localized</i> on RB-o part, whereas in <b>RB–NDI</b> the triplet state is <i>delocalized</i> on both the NDI and RB-o units. The ISC of spin converter was not outcompeted by RET. These studies are useful for switching of triplet excited state

Associations between TNFSF4 gene polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and susceptibility to autoimmune diseases in Asians: a meta-analysis

Background: Tumor necrosis factor superfamily member 4 (TNFSF4) has significant role in modulating autoimmune diseases (ADs) and single nucleotide polymorphism (SNP) is also related with the susceptibility to some diseases. So a meta-analysis aimed at systematically assessing the associations between TNFSF4 polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and ADs risk was performed in Asians. Methods: Total 14 eligible articles published before March 2019 involving 35 studies, of which 21 studies (16,109 cases and 26,378 controls) for rs2205960 G > A, 8 studies (2,424 cases and 3,692 controls) for rs704840 T > G, and 6 studies (3,839 cases and 5,867 controls) for rs844648 G > A were included. Effects of the three respective polymorphisms on the susceptibility to ADs were estimated by pooling the odds ratios (ORs) with their corresponding 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous and homozygous models. Results: The overall analysis revealed that all the rs2205960 G > A, rs704840 T > G and rs844648 G > A polymorphisms could increase the risk of ADs in allelic, dominant, recessive, heterozygous and homozygous models. Furthermore, subgroup analysis showed that both rs2205960 G > A and rs704840 T > G were significantly associated with the susceptibility to systemic lupus erythematosus (SLE). What’s more, statistically significant association between rs2205960 G > A polymorphism and primary Sjögren’s syndrome (pSS) susceptibility was also observed in allelic, dominant and heterozygous models. Conclusions: This current meta-analysis suggested that all of the three TNFSF4 polymorphisms may be associated with ADs susceptibility in Asians.</p

ERα bounds to <i>CLOCK</i> promoter regions in response to E2.

<p>A, Schematic representation of the ERE sites within the <i>CLOCK</i> promoter regions in the CLOCK-WT-Luc constructs. Constructs containing wild-type promoter and mutant promoters (truncation) are shown. Luciferase activity of MCF-7 cells transfected with the indicated constructs together with or without shERα#1 are shown on the right. B, CLOCK luciferase reporter constructs containing wild-type and mutant CLOCK promoters with point mutation in the EREs are shown, together with the luciferase activity of HeLa cells transfected with one of these constructs together with or without ERα. A and B, all experiments were performed in triplicate and repeated at least three times, and the data shown are the means ± SDs. <i>P</i> value was determined by ANOVA with Bonferroni test (*, <i>P</i><0.05. ns, not significant). C, ChIP assay showing the recruitment of ERα on <i>CLOCK</i> promoter regions. MCF-7 cells were grown in phenol red-free medium and charcoal striped FCS medium for 2 days and the cells were then treated with vehicle or 1 µM E2 concentrations for 1 h, followed by ChIP assay using antibody against ERα or IgG. Total input DNA at a 1∶10 dilution was used as a positive control for the PCR reaction. Immunoprecipitated DNA was analyzed by PCR with primers specific for <i>CLOCK</i>, the relative positions of which are shown in the right panel of Figure 5C. All experiments were repeated at least of three times.</p

Codelivery of High-Molecular-Weight Poly-porphyrins and HIF-1α Inhibitors for <i>In Vivo</i> Synergistic Anticancer Therapy

Photodynamic therapy (PDT) is showing great potential in the treatment of cancer diseases, and photosensitizers play crucial roles in absorbing the energy of light and generating reactive oxygen species (ROS) during PDT. Most of the photosensitizers bearing macrocyclic structures have strong hydrophobicity and suffer from the π–π interaction and undesired aggregation caused quenching (ACQ), which severely limit the PDT efficacy. Moreover, the continuous oxygen consumption during PDT also leads to the upregulated expression of hypoxia-inducible factor-1α (HIF-1α), which can aggravate the growth of tumors. To overcome the abovementioned problems, polymerized photosensitizers repelled by flexible thioketal linkers were designed and synthesized using a multicomponent polymerization (MCP) method to afford the poly-porphyrins with high molecular weight (Mw > 20 000 g/mol) under room temperature. The ACQ effect could be significantly inhibited by introducing flexible chains and increasing Mw, leading to the improvement in the singlet oxygen quantum yield and phototoxicity simultaneously. An HIF-1α inhibitor, Lificiguat (YC-1) was synthesized as a chemodrug and codelivered with poly-porphyrins to decrease the expression of HIF-1α and inhibit tumor growth under hypoxia. With the synergistic PDT and chemotherapy, poly-porphyrin/YC-1 micelles showed excellent therapeutic antitumor efficacy both in vitro and in vivo

CLOCK promotes MCF-7 cells proliferation.

<p>Cells were transfected with control shRNA (shCon), shCLOCK or shERα#1 in the presence or absence of E2 for six or seven days followed by MTT assay or crystal violet staining. MTT assay of MCF-7 (A) and T47D (B) cells. The cells were treated with E2 for six days. C, Crystal violet staining (MCF-7 cells). The cells were treated with E2 for seven days. Viable colonies were stained with 0.1% crystal violet and photographed. The dye taken up by the colonies were solubilized in 10% SDS and quantified by absorbance at 570 nm. Representative images are shown on the left panel of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095878#pone-0095878-g006" target="_blank">Figure 6C</a>, and the corresponding quantitative analyses are shown on the right panel. Only representative data from three independent experiments are shown. D, Representative colonies of each experimental group are shown. MCF-7 cells transfected with pcDNA3, pcDNA3-CLOCK or pcDNA3-ERα were selected in the presence of 1 µg/ml G418 for 2 weeks. The cells were then collected and subjected to a soft agar colony culture. Photographs of the colonies were taken one week after seeding. All experiments were repeated at least three times. A-C, Data are the means ± SDs. <i>P</i> value was determined by ANOVA with Bonferroni test (*, <i>P</i><0.05).</p

Proposed model showing the crosstalk between E2-ERα signaling and circadian rhythm.

<p>Proposed model showing the crosstalk between E2-ERα signaling and circadian rhythm.</p