Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer. Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells. Results: Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells. Conclusion: Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways

Predicting Disease-Related Genes Using Integrated Biomedical Networks

Background: Identifying the genes associated to human diseases is crucial for disease diagnosis and drug design. Computational approaches, esp. the network-based approaches, have been recently developed to identify disease-related genes effectively from the existing biomedical networks. Meanwhile, the advance in biotechnology enables researchers to produce multi-omics data, enriching our understanding on human diseases, and revealing the complex relationships between genes and diseases. However, none of the existing computational approaches is able to integrate the huge amount of omics data into a weighted integrated network and utilize it to enhance disease related gene discovery. Results: We propose a new network-based disease gene prediction method called SLN-SRW (Simplified Laplacian Normalization-Supervised Random Walk) to generate and model the edge weights of a new biomedical network that integrates biomedical data from heterogeneous sources, thus far enhancing the disease related gene discovery. Conclusions: The experiment results show that SLN-SRW significantly improves the performance of disease gene prediction on both the real and the synthetic data sets

On the existence and uniqueness of solutions to stochastic differential equations driven by G-Brownian motion with integral-Lipschitz coefficients

In this paper, we study the existence and uniqueness of solutions to stochastic differential equations driven by G-Brownian motion (GSDEs) with integral-Lipschitz conditions on their coefficients

Relationship between the structure and composition of rumen microorganisms and the digestibility of neutral detergent fibre in goats

Publication history: Accepted - 7 June 2018; Published online - 26 July 2018; Published print - January 2019.Objective: This experiment was conducted to compare the structure and composition of ruminal microorganisms in goats with high and low neutral detergent fibre (NDF) digestibility. Methods: Nineteen crossbred goats were used as experimental animals and fed the same total mixed rations during the 30-day pre-treatment and 6-day digestion trialperiods. All faeces were collected during the digestion period for measuring the NDF digestibility. Then, high and the low NDF digestibility individuals were chosen for the high NDF digestibility group (HFD) and low NDF digestibility group (LFD), respectively. Rumen contents were collected for total microbial DNA extraction. The V4 region of the bacterial 16S rRNA gene was amplified using universal primers of bacteria and sequenced using high-throughput sequencer. The sequences were mainly analysed by QIIME 1.8.0. Results: A total of 18,694 operational taxonomic units were obtained, within 81.98% belonged to bacteria, 6.64% belonged to archaea and 11.38% was unassigned microorganisms. Bacteroidetes, Firmicutes, and Proteobacteria were the predominant microbial phyla in both groups. At the genus level, the relative abundance of fifteen microorganisms were significantly higher (p<0.05) and six microorganisms were extremely significantly higher (p<0.01) in LFD than HFD. Overall, 176 core shared genera were identified in the two groups. The relative abundance of 2 phyla, 5 classes, 10 orders, 13 families and 15 genera had a negative correlation with NDF digestibility, but only the relative abundance of Pyramidobacter had a positive correlation with NDF digestibility. Conclusion: There were substantial differences in NDF digestibility among the individual goats, and the NDF digestibility had significant correlation with the relative abundance of some ruminal microorganisms.The authors would like to thank the National Key R&D Program of China (grant number: 2017YFD0502005) and Sichuan Beef Cattle Innovation Team (grant number: 035Z389) for the financial support

Bacterial Community Diversity Associated With Different Utilization Efficiencies of Nitrogen in the Gastrointestinal Tract of Goats

The objective of this study was to examine the association between bacterial community structure and the utilization efficiency of nitrogen (UEN) phenotypes by determining the bacterial community in the gastrointestinal tract (GIT) of goats that differ in UEN using high-throughput 16S rRNA gene sequencing. Thirty Nubian goats were selected as experimental animals, and their UEN was determined in a metabolic experiment. Subsequently, eight individuals were grouped into the high nitrogen utilization (HNU) phenotype, and seven were grouped into the low nitrogen utilization (LNU) phenotype. The bacterial 16S rRNA gene amplicons from the rumen, abomasum, jejunum, cecum and colon contents of these animals were sequenced using next-generation high-throughput sequencing technology. Two hundred thirty-nine genera belonging to 23 phyla in the rumen, 319 genera belonging to 30 phyla in the abomasum, 248 genera belonging to 36 phyla in the jejunum, 248 genera belonging to 25 phyla in the colon and 246 genera belonging to 23 phyla in the cecum were detected, with Bacteroidetes and Firmicutes predominating. In addition, a significant correlation was observed between the UEN and the genera Succiniclasticum, Bacteroides, Ruminobacter, Methanimicrococcus, Mogibacterium, Eubacterium_hallii_group and Ruminococcus_1 in the rumen; Bacteroidales_S24-7_group, Bacteroidales_RF16_group, Bacteroidales_UCG-001 and Anaerovibrio in the abomasum; Ruminococcus_2, Candidatus_Saccharimonas, Candidatus_Arthromitus and Coprococcus_1 in the jejunum; Erysipelotrichaceae_UCG-004, Akkermansia, Senegalimassilia, Candidatus_Soleaferrea and Methanocorpusculum in the colon; and Ruminococcaceae_UCG-002, Anaerovibrio and Ruminococcaceae_UCG-007 in the cecum. Furthermore, the real-time PCR results showed that the ruminal copies of Fibrobacter_succinogenes, Butyrivibrio_fibrisolvens, Ruminococcus_sp._HUN007, Prevotella ruminicola and Streptococcus bovis in the HNU animals were significantly higher than those in the LNU animals. This study suggests an association of GIT microbial communities as a factor that influences UEN in goats

Sufentanil for carboprost-induced adverse reactions during cesarean delivery under combined spinal-epidural anesthesia

Objective: Carboprost plays an important role in managing refractory uterine atony and severe postpartum hemorrhage. However, it is associated with challenging adverse reactions. We aimed to evaluate the clinical effects of low-dose sufentanil on the prevention of adverse events associated with carboprost during cesarean delivery. Study Design: Patients were randomly divided into two groups: a placebo control group (group C, n = 15) that received an intravenous infusion of 1 mL of normal saline 2 min before carboprost and a sufentanil group (group S, n = 15) that received 5 µg of sufentanil. The primary outcome was the incidence of nausea and vomiting following carboprost administration. Results: The incidence of nausea, vomiting, and gastrointestinal discomfort was significantly lower in group S than in group C (P &lt; 0.05). Conclusions: The prophylactic use of low-dose sufentanil reduces the incidence of gastrointestinal side effects caused by carboprost administration during cesarean section

Intermolecular Failure of L-type Ca(2+) Channel and Ryanodine Receptor Signaling in Hypertrophy

Pressure overload–induced hypertrophy is a key step leading to heart failure. The Ca(2+)-induced Ca(2+) release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+) channel (LCC) and ryanodine receptors (RyRs) in aortic stenosis rat models of compensated (CHT) and decompensated (DHT) hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of “intermolecular failure.” Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+) release, visualized as “Ca(2+) spikes,” became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+) transients in CHT. These data suggested that, within a certain limit, termed the “stability margin,” mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of “hidden” intermolecular failure in CHT has important clinical implications