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Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract
Xiu-Feng Huang,Lue Xiang,Wan Cheng,Fei-Fei Cheng,Kai-Wen He,Bo-Wen Zhang,Si-Si Zheng,Ru-Yi Han,Yi-Han Zheng,Xiao-Tao Xu,Huan-Yun Yu,Wenjuan Zhuang,Yuk Fai Leung,Zi-Bing Jin 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p. R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholinooligonucleotide- induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.
A novel M2e-multiple antigenic peptide providing heterologous protection in mice
Feng Wen,Ji-Hong Ma,Hai Yu,Fu-Ru Yang,Meng Huang,Yan-Jun Zhou,Ze-Jun Li,Xiu-Hui Wang,Guo-Xin Li,Yi-Feng Jiang,Wu Tong,Guangzhi Tong 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.1
Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.
A Strategy to Protect Al<sub>2</sub>O<sub>3</sub>-based PFC Decomposition Catalyst from Deactivation
Xu, Xiu-Feng,Jeon, Jong Yeol,Choi, Mi Hwa,Kim, Hee Young,Choi, Won Choon,Park, Yong-Ki The Chemical Society of Japan 2005 Chemistry letters Vol.34 No.3
<P>γ-Al<SUB>2</SUB>O<SUB>3</SUB> is one of the most active catalysts for hydrolytic decomposition of PFCs but it has been suffered from deactivation. The main reason for the deactivation was the transformation of catalytically active γ-phase into an inactive α-phase by the HF produced during the decomposition of PFCs. To prohibit the phase transformation, structure modifiers such as ZnAl<SUB>2</SUB>O<SUB>4</SUB> and AlPO<SUB>4</SUB> were strongly required, which resulted in a remarkable catalyst durability.</P>
효소발효 백하수오의 고지혈증 흰쥐에 대한 지질대사 개선 효능 연구
풍수김 ( Xiu Jin Feng ),노성수 ( Seong Soo Roh ),오당섭 ( Dang Seop Oh ),서영배 ( Young Bae Seo ) 대한본초학회 2015 大韓本草學會誌 Vol.30 No.6
Objectives : The present study was conducted to examine whether Cynanchi wilfordii radix (CWR) with or without fermentation has an ameliorative effect on hyperlipidemia in rats. Methods : We analyzed the contents of Conduritol F on Cynanchi wilfordii radix. The experimental animals were divided into six groups; normal diet fed group (N), high cholesterol fed control group (Con), Lovastatin 20 mg/kg (L), CWR-W 300 mg/kg (CWR-W), and CWR-F 300 mg/kg on hyperlipidemia model induced by feeding 1.25% cholesterol. Rats were administrated orally every day for 8 weeks. And lipid profile of serum and weight change were observed. Results : The vehicle displayed a markedly increased body weight and significantly increased liver and epididymal fat weight, however, the administration of CWR improved the body, liver, and epididymal fat weights. All drug treatment reduced significantly the serum level of total cholesterol and LDL-cholesterol elevated by intake of high cholesterol diet. TG displayed a reducing tendency all drug treatment, however, CWR-W decreased significantly. Atherogenic index and cardiac risk factor increased high cholesterol diet fed control group, while the administration of CWR-W and CWR-F decreased significantly. The major index of liver injury such as AST and ALT improved in all drug treatment. Conclusions : These results suggest that CWR extended the effect of lipid enhanced. Therefore CWR with or without fermentation may be useful for therapeutic treatment of clinical conditions associated with hyperlipidemia. Finally, these require more investigations about the action mechanism of CWR in the future.
Shi-Xiu Feng,Caigan Du,Qiunong Guan,Tao Chen 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.7
Medicinal herbs are the preferred candidates for drug discovery against human diseases including cancer. The roots of Prismatomeris connata have been used in traditional herbal medicine to treat many health problems, particularly pneumoconiosis. This study was to test the anti-tumor activity of 3-Hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone (PCON6), a major anthraquinone derivative from C. connata, against lung cancer. Cell viability in cultures was assessed by MTT assay. Cell death or apoptosis was determined with Annexin-V and 7-Aminoactinomycin D staining. Cell cycle was analyzed by both propidium iodide DNA staining and BrdU incorporation assay. Here we showed that in a panel of fifteen different tumor cells lines, a group of four non-small cell lung carcinoma (NSCLC) cell lines exhibited a relatively higher sensitivity to PCON6 growth inhibition than the rest of most non-lung cancer cell lines (p = 0.0461). Further studies demonstrated that the suppression of NSCLC H520 cell growth by PCON6 was associated with its induction of apoptosis at 20 μM (p = 0.0008), and of cell accumulation at S phase cell cycle (p < 0.05) that was further supported by a decrease in cdc2 protein expression. This preliminary study suggests that natural compound PCON6 has relatively selective cytotoxicity against NSCLC growth and represent a concept of developing a novel drug therapy specific for NSCLC based on the roots of C. connata or PCON6.
Nrf2 Overexpression Predicts Prognosis and 5-FU Resistance in Gastric Cancer
Hu, Xiu-Feng,Yao, Jun,Gao, She-Gan,Wang, Xin-Shuai,Peng, Xiu-Qing,Yang, Yan-Tong,Feng, Xiao-Shan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9
Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.