Negative Feedback Regulation of Wnt4 Signaling by EAF1 and EAF2/U19

Previous studies indicated that EAF (ELL-associated factor) family members, EAF1 and EAF2/U19, play a role in cancer and embryogenesis. For example, EAF2/U19 may serve as a tumor suppressor in prostate cancer. At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt 4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence and extension movements in zebrafish embryos through Wnt maintenance. Here, we used zebrafish embryos and mammalian cells to show that both EAF1 and EAF2/U19 were up-regulated by Wnt4 (Wnt4a). Furthermore, we found that EAF1 and EAF2/U19 suppressed Wnt4 expression by directly binding to the Wnt4 promoter as seen in chromatin immunoprecipitation assays. These findings indicate that an auto-regulatory negative feedback loop occurs between Wnt4 and the EAF family, which is conserved between zebrafish and mammalian. The rescue experiments in zebrafish embryos showed that early embryonic development required the maintenance of the appropriate levels of Wnt4a through the feedback loop. Others have demonstrated that the tumor suppressors p63, p73 and WT1 positively regulate Wnt4 expression while p21 has the opposite effect, suggesting that maintenance of appropriate Wnt4 expression may also be critical for adult tissue homeostasis and prevention against tumor initiation. Thus, the auto-regulatory negative feedback loop that controls expression of Wnt4 and EAF proteins may play an important role in both embryonic development and tumor suppression. Our findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo

Leukotriene B4, administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs

<p>Abstract</p> <p>Background</p> <p>Despite intensive studies focused on the pathophysiology of asthmatic inflammation, little is known about how cross-talk between neuroendocrine and immune systems regulates the inflammatory response during an asthmatic attack. We recently showed corresponding changes of cytokines and leukotriene B₄(LTB₄) in brain and lung tissues of antigen-challenged asthmatic rats. Here, we investigated how LTB₄interacts with the neuroendocrine-immune system in regulating antigen-induced asthmatic responses in sensitized guinea pigs.</p> <p>Methods</p> <p>Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Vehicle, LTB₄or U75302 (a selective LTB₄BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v.) 30 min before challenge. Airway contraction response was evaluated using Penh values before and after antigen challenge. The inflammatory response in lung tissue was evaluated 24 h after challenge. The LTB₄content of lung and brain homogenate preparations was detected by reversed phase high-performance liquid chromatography (RP-HPLC). Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA kits.</p> <p>Results</p> <p>Antigen challenge impaired pulmonary function and increased inflammatory cell infiltration in lung tissue. These responses could be significantly suppressed by LTB₄, 30 ng i.c.v., in ovalbumin-sensitized guinea pigs. LTB₄content of lung and brain homogenates from antigen-challenged guinea pigs was significantly increased. In addition, administration of LTB₄via i.c.v. markedly increased CORT and ACTH level in plasma before antigen challenge, and there were further increases in CORT and ACTH levels in plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the effects of LTB₄. In addition, U75302, 100 ng via i.c.v. injection, markedly decreased LTB₄content in lung homogenates, but not in brain homogenates.</p> <p>Conclusions</p> <p>Increased LTB₄levels in brain during asthmatic attacks down-regulates airway contraction response and inflammation through the BLT1 receptor. Stimulation of the hypothalamic-pituitary-adrenal axis by LTB₄may result in an increase in systemic glucocorticoids which, in turn, would feed back to suppress the asthmatic response.</p

排卵功能障碍性不孕症患者的中医五态人格及焦虑分析

Objective: Finding out the relationship between five-pattern personality and anxiety 、depression characteristics of the DOI patients. Methods: 200 DOI patients were selected in the Infertility Specialist of Guangzhou Liwan District Hospital of Chinese Medicine，at the same time, researchers choose normal women as controls. Respondents filled in the Five-pattern Personality Scales、SAS、SDS and general information questionnaire. Results: The proportion of shaoyin personality of the DOI patients(50%) is significantly higher than the normal women(22%). And no yin and yang personality was observed in patients with DOI. The SAS and SDS score of the DOI patients, listed in descending order, is as follow, taiyin personality、shaoyin personality、taiyang personality、shaoyang personality、yin and yang personality. Conclusion: The main five-pattern personality of DOI is shaoyin personality. The patients of the taiyin and shaoyin personality are more likely to have the characteristics of anxiety and depression.目的  探究排卵功能障碍性不孕症患者不同中医五态人格类型与焦虑、抑郁情绪的关联性。方法  确诊为排卵功能障碍性不孕症患者200例，同时在本院选择正常已育妇女作为对照组。采用《五态人格量表》、《焦虑自评量表（SAS）》、《抑郁自评量表（SDS）》及一般资料问卷进行调查。结果  排卵功能障碍性不孕症组中少阴型中医人格（50%）明显高于正常妇女组（22%），且没有出现阴阳平和型中医人格。不孕症组中太阳、少阳、少阴、太阴型中医人格的焦虑、抑郁总分4组间不全相等（P＜0.001）。结论  排卵功能障碍性不孕症患者以少阴型中医人格为主，且太阴、少阴型中医人格的患者更易出现高焦虑、高抑郁

Open circuit voltage and state of charge relationship functional optimization for the working state monitoring of the aerial lithium-ion battery pack.

The aerial lithium-ion battery pack works differently from the usual battery packs, the working characteristic of which is intermittent supplement charge and instantaneous large current discharge. An adaptive state of charge estimation method combined with the output voltage tracking strategy is proposed by using the reduced particle - unscented Kalman filter, which is based on the reaction mechanism and experimental characteristic analysis. The improved splice equivalent circuit model is constructed together with its state-space description, in which the operating characteristics can be obtained. The relationship function between the open circuit voltage and the state of charge is analyzed and especially optimized. The feasibility and accuracy characteristics are tested by using the aerial lithium-ion battery pack experimental samples with seven series-connected battery cells. Experimental results show that the state of charge estimation error is less than 2.00%. The proposed method achieves the state of charge estimation accurately for the aerial lithium-ion battery pack, which provides a core avenue for its high-power supply security

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.</p> <p>Purpose</p> <p>To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.</p> <p>Methods</p> <p>45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.</p> <p>Results</p> <p>Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).</p> <p>Conclusions</p> <p>Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.</p

Genetic variation analysis of reemerging porcine epidemic diarrhea virus prevailing in central China from 2010 to 2011

Porcine epidemic diarrhea has re-emerged with devastating impact in central China since October 2010. To investigate and analyze the reason of this outbreak, the M and ORF3 genes of 15 porcine epidemic diarrhea viruses (PEDV), which were collected from different areas of central China during October 2010 and December 2011, were amplified by reverse transcriptase polymerase chain reaction, cloned, sequenced, and analyzed. Sequence analyses showed that the nucleotides and amino acids were changed at some sites in the M and ORF3 genes of the 15 PEDV strains compared with those genes of CV777 reference strain. Based on the phylogenetic analyses, PEDVs in central China and reference strains could be separated into three groups: G1, G2, and G3. The 15 PEDV strains belonged to G3 group and showed a close relationship with Korean strains (2007), Thai strains (2007–2008), and partial other Chinese strains (2010–2011), but differed genetically from European strains (Br1/87) and the vaccine strain (CV777 vs) being used in China. Furthermore, all 15 PEDV strains from central China and some other isolates in China from 2003 to 2007 (LJB-03, QH, and LZC) belonged to different group. Therefore, PEDV exhibits rapid variation and genetic evolution, and the currently prevailing PEDV strains in central China are a new genotype

Chitosan-Alginate Sponge: Preparation and Application in Curcumin Delivery for Dermal Wound Healing in Rat

A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM. The swelling ability, in vitro drug release and degradation behaviors, and an in vivo animal test were employed to confirm the applicability of this sponge as a wound dressing material. As the chitosan content in the sponge decreased, the swelling ability decreased. All types of the sponges exhibited biodegradable properties. The release of curcumin from the sponges could be controlled by the crosslinking degree. Curcumin could be released from the sponges in an extended period for up to 20 days. An in vivo animal test using SD rat showed that sponge had better effect than cotton gauze, and adding curcumin into the sponge enhanced the therapeutic healing effect