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Background Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. In this study, we investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells. Methods The anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin. Results Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21 Cip1 (p21) and p27 kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c . Conclusion Taken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer.

Background Multidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mechanism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efflux transporters. Sulbactam, a β-lactamase inhibitor, is generally combined with β-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the first study to report the effects of sulbactam on mammalian cells. Methods We used the breast cancer cell lines as a model system to determine whether sulbactam affects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC–MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux assay. Results MTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced. The mRNA expression levels of ABC transporters were also decreased when treated with doxorubicin and sulbactam. The doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin efflux. Conclusions The combination of sulbactam and doxorubicin enhances the cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the expression of ABC transporter proteins and proteins associated with the process of transcription and initiation of translation, and blocking the efflux of doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast cancer treatment to decrease the prescribed dose of doxorubicin to avoid the adverse effects of doxorubicin.

Intracellular Ca ²⁺ transient is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but whether voltage-gated Ca ²⁺ channels are involved remains uncertain. Here, we show that the T-type voltage-gated Ca ²⁺ channel Ca ᵥ3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Ca ᵥ3.2 ⁻/⁻) show congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Ca ᵥ3.2 overexpression in ATDC5 cells enhances chondrogenesis, which could be blunted by both blocking T-type Ca ²⁺ channels and inhibiting calcineurin and suggests that Ca ᵥ3.2 is responsible for Ca ²⁺ influx during chondrogenesis. Finally, the expression of sex determination region of Y chromosome (SRY)-related high-mobility group-Box gene 9 (Sox9), one of the earliest markers of committed chondrogenic cells, is reduced in Ca ᵥ3.2 ⁻/⁻ tracheas. Mechanistically, Ca ²⁺ influx via Ca ᵥ3.2 activates the calcineurin/nuclear factor of the activated T-cell (NFAT) signaling pathway, and a previously unidentified NFAT binding site is identified within the mouse Sox9 promoter using a luciferase reporter assay and gel shift and ChIP studies. Our findings define a previously unidentified mechanism that Ca ²⁺ influx via the Ca ᵥ3.2 T-type Ca ²⁺ channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during tracheal chondrogenesis.

•We present antibiotic-induced membrane thinning of a multi-lamellar thin film sample.•Both penicillin and sulbactam are found positioned outside the model membrane in an aqueous solution.•We demonstrate a hybrid method to study the antibiotic–membrane interaction. Antibiotic drug resistance is a serious issue for the treatment of bacterial infection. Understanding the resistance to antibiotics is a key issue for developing new drugs. We used penicillin and sulbactam as model antibiotics to study their interaction with model membranes. Cholesterol was used to target the membrane for comparison with the well-known insertion model. Lamellar X-ray diffraction (LXD) was used to determine membrane thickness using successive drug-to-lipid molar ratios. The aspiration method for a single giant unilamellar vesicle (GUV) was used to monitor the kinetic binding process of antibiotic–membrane interactions in an aqueous solution. Both penicillin and sulbactam are found positioned outside the model membrane, while cholesterol inserts perpendicularly into the hydrophobic region of the membrane in aqueous solution. This result provides structural insights for understanding the antibiotic–membrane interaction and the mechanism of antibiotics.

Traditional post-level opinion classification methods usually fail to capture a person’s overall sentiment orientation toward a topic from his/her microblog posts published for a variety of themes related to that topic. One reason for this is that the sentiments connoted in the textual expressions of microblog posts are often obscure. Moreover, a person’s opinions are often influenced by his/her social network. This study therefore proposes a new method based on integrated information of microblog users’ social interactions and textual opinions to infer the sentiment orientation of a user or the whole group regarding a hot topic. A Social Opinion Graph ( SOG ) is first constructed as the data model for sentiment analysis of a group of microblog users who share opinions on a topic. This represents their social interactions and opinions. The training phase then uses the SOGs of training sets to construct Sentiment Guiding Matrix ( SGM ), representing the knowledge about the correlation between users’ sentiments, Textual Sentiment Classifier ( TSC ), and emotion homophily coefficients of the influence of various types of social interaction on users’ mutual sentiments. All of these support a high-performance social sentiment analysis procedure based on the relaxation labeling scheme. The experimental results show that the proposed method has better sentiment classification accuracy than the textual classification and other integrated classification methods. In addition, IMSA can reduce pre-annotation overheads and the influence from sampling deviation.

ObjectiveTo evaluate the effect of electroacupuncture (EA) in a rat model of chronic steroid-induced insulin resistance (SIIR).MethodsAn SIIR rat model was created using daily intraperitoneal injections of clinically relevant doses of dexamethasone (1 mg/kg) for 5 days to induce chronic insulin resistance. Thirty-six SIIR rats were randomly divided into the SIIR+EA group (n=18), which received 15 Hz EA at ST36 for 60 min, and the SIIR group (n=18), which remained untreated. Plasma glucose and free fatty acid (FFA) levels were measured in serial blood samples taken without further manipulation (n=6 per group) and during insulin challenge test (ICT, n=6 per group) and intravenous glucose tolerance test (ivGTT, n=6 per group). Insulin receptor substrate (IRS)-1 and glucose transporter (GLUT)-4 were measured using Western blotting and expressed relative to β-actin.ResultsFollowing EA, area-under-the-curve (AUC) for glucose was reduced (7340±291 vs 10 705±1474 mg/dL/min, p=0.049) and FFA levels significantly lower at 30/60 min in the SIIR+EA versus SIIR groups. Similar effects on glucose AUC were seen during the ICT (5568±275 vs 7136±594 mg/dL/min, p<0.05) and igVTT (11 498±1398 vs 16 652±1217 mg/dL/min, p<0.01). FFA levels were lower at 30 and/or 60 min in SIIR+EA versus SIIR groups (p<0.01). Relative expression of IRS-1 and GLUT4 were significantly increased by EA (p<0.01).ConclusionsEA decreased the FFA level and increased insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA is an effective alternative treatment for the reduction of insulin resistance in patients requiring chronic use of dexamethasone.

Background and aimPrevious animal studies have reported a glucose-lowering effect of electroacupuncture (EA) and suggested that the mechanisms are closely related to intracellular signalling pathways. The aim of this study was to screen for potential intracellular signalling pathways that are upregulated by EA at ST36 bilaterally in rats with diabetes mellitus (DM) using microarray analysis.MethodsStreptozotocin (STZ)-induced diabetic rats were randomly assigned to experimental (EA, n=8) or control (non-EA, n=8) groups. Plasma glucose levels were measured at baseline and after 30 and 60 min, and microarray analysis was performed on samples of gastrocnemius muscle.ResultsRelative to baseline values, EA significantly reduced plasma levels of glucose at 30 and 60 min. The microarray pathway analysis showed that cell adhesion molecules and type 1 DM gene sets were both upregulated in EA versus non-EA groups (p<0.05).ConclusionsCell adhesion molecules might be related to the glucose-lowering effect induced by EA in rats with STZ-induced type 1 diabetes. Further research will be required to examine the involvement of related intracellular signalling pathways.

Purpose - The purpose of this paper is to propose an energy-proportional routing (EPR) algorithm, which effectively extends the lifetimes of sensor networks. Design/methodology/approach - The algorithm makes no specific assumption on network topology and hence is suitable for improving sensor networks with clustering. To optimally utilize energy, light-load units - nodes or clusters that conserve energy are ideal candidates as intermediate units for forwarding data from others. To balance the load, first, the proposed algorithm predicts energy consumption of each node in each round. Then the algorithm controls the energy consumption of each unit as close as possible to the threshold representing the energy utilization mean value among clusters. Finally the algorithm checks satisfaction of the energy constraints in terms of distances and predicted data amounts. The proposed algorithm performs routing by determining whether a cluster head or a node should either undertake forwarding tasks or transmit data to intermediate hops. In this way, energy dissipation is evenly distributed to all units and the lifetime of the whole wireless sensor network is ultimately extended. Findings - The algorithm applies hierarchically to different levels of network topology. In addition to experiments, the mathematical proofs of lifetime extension by the proposed routing algorithm are given in accordance with three widely accepted criteria - total energy dissipation, the number of live nodes in each round and the throughput (data amount per round). Originality/value - A new routing algorithm is proposed.

During assembly of the spliceosome, the U4 small nuclear RNA (snRNA) interacts with the spliceosome as a preformed U4/U6-U5 triple small nuclear ribonucleoprotein (snRNP) complex. Subsequently, U4 becomes loosely associated with the spliceosome, whereas U5 and U6 remain tightly associated, suggesting unwinding of the U4/U6 duplex. We show that this step of the assembly process can be blocked by limiting the ATP concentration in the splicing reaction. We also show that the yeast precursor mRNA processing protein PRP19 becomes associated with the spliceosome during this transition. Thus, PRP19 may function in this step of spliceosome assembly.