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991.
Background
The diagnosis of idiopathic pulmonary fibrosis can be quite challenging, even after careful clinical evaluation, imaging and pathological tests. This case report intends to demonstrate and discuss these difficulties, especially those concerning the differential diagnosis with chronic hypersensitivity pneumonitis.Case presentation
A 58-year-old white male presented with shortness of breath, dry cough, fatigue and weight loss for two months. He was a former smoker and had regular exposure to a parakeet and poultry. Physical examination revealed bilateral basal crackles and chest imaging showed subpleural cystic lesions and traction bronchiectasis with a right side and upper level predominance. Auto-antibodies and IgG immunoglobulins to parakeet and fungal proteins were negative. Lung function tests displayed moderate restriction, low diffusion capacity and resting hypoxaemia. Bronchoalveolar lavage showed increased lymphocytes (28%) and neutrophils (12%) and surgical lung biopsy was compatible with a pattern of usual interstitial pneumonia. According to the possibility of either idiopathic pulmonary fibrosis or chronic hypersensitivity pneumonitis, treatment included prednisolone, azathioprine, acetylcysteine and avoidance of contact with the parakeet, but there was an unfavorable response and the patient was subsequently referred for lung transplant.Conclusion
Chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis can present with the same clinical and radiological manifestations In this case, despite careful evaluation, no definite diagnosis could be achieved.992.
Na-Na Du Zong-Gen Peng Chong-Wen Bi Sheng Tang Ying-Hong Li Jian-Rui Li Yan-Ping Zhu Jing-Pu Zhang Yan-Xiang Wang Jian-Dong Jiang Dan-Qing Song 《PloS one》2013,8(3)
Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations. 相似文献
993.
Xiaofeng Luo Song Duan Qixiang Duan Yongcheng Pu Yuecheng Yang Yingying Ding Meiyang Gao Na He 《PloS one》2013,8(4)
Objective
To examine alcohol use and subsequent HIV risky behaviors among a sample of predominately ethnic minority people living with HIV/AIDS (PLWHA) in a rural community in Yunnan Province, China.Method
A cross-sectional study with a face-to-face questionnaire interview was conducted among eligible participants.Results
In total, 455 (94.4%) out of 482 eligible HIV patients participated in the study. Of them, 82.6% were ethnic minorities; 15.4% were never married; 96.5% were sexually experienced; 55.4% had used drugs, 67% were receiving antiretroviral therapy (ART). Over 65% were ever drinkers; of whom 61.5% were current drinkers. Among current drinkers, 32.4% drank daily and 41.2% were hazardous drinkers. Chinese white wine was the preferred choice. Higher level of alcohol use among drinkers in the preceding month was positively associated with being males (OR = 2.76, 95%CI: 1.03–7.43), ethnic minorities (OR Jingpo = 2.21, 95%CI: 1.06–4.59; OR other minorities = 3.20, 95%CI: 1.34–7.62), higher education (OR1–6 = 1.98, 95%CI: 0.99–3.96; OR≥7 = 2.35, 95%CI: 1.09–5.06) and being ART-naive (OR = 2.69, 95%CI: 1.67–4.32). About 39% of ever drinkers reported having engaged in sex after drinking since HIV diagnosis. Those who were younger than 46 years (OR16–25 = 7.77, 95%CI: 1.22–49.60, OR26–35 = 2.79, 95%CI: 1.06–7.35, OR36–45 = 2.96, 95%CI: 1.57–7.58), hazardous drinkers (OR = 1.99, 95%CI: 1.00–3.97) and drug users (OR = 3.01, 95%CI: 1.19–7.58) were more likely to have had sex after drinking. Approximately 56% of drug users had used drugs after drinking.Conclusions
High prevalence of alcohol use and subsequent risky behaviors including sexual engagement and drug use among HIV patients in rural Yunnan require tremendous and integrated efforts for prevention and control of alcohol and drug abuse and HIV spreading. 相似文献994.
Yan Zhen Yanfen Ye Xiaoli Yu Chunping Mai Ying Zhou Yan Chen Huiling Yang Xiaoming Lyu Ye Song Qiangyun Wu Qiaofen Fu Mengyang Zhao Shengni Hua Hao Wang Zhen Liu Yajie Zhang Weiyi Fang 《PloS one》2013,8(6)
Background
The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC).Experimental design
CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP) tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored.Results
NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT) and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC.Conclusion
Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC. 相似文献995.
Hussam H. Shaheen Bianka Prinz Ming-Tang Chen Tej Pavoor Song Lin Nga Rewa Houston-Cummings Renee Moore Terrance A. Stadheim Dongxing Zha 《PloS one》2013,8(7)
State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered
Pichia
pastoris
that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored "bait" Fc, which results in targeting functional “half” IgGs to the cell wall of
Pichia
pastoris
without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered
Pichia
pastoris
, this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle. 相似文献
996.
Lili Jiang Libing Song Jueheng Wu Yi Yang Xun Zhu Bo Hu Shi-Yuan Cheng Mengfeng Li 《PloS one》2013,8(1)
Angiogenesis in glioma is associated with the poor prognosis of the disease and closely correlates with the highly invasive phenotype of glioma cells, which represents the most challenging impediment against the currently glioma treatments. Bmi-1, an onco-protein, has been implicated in the progression of various human cancers, including gliomas, whereas its role in glioma angiogenesis remains unclear. Our current study examined the effects of Bmi-1 on glioma angiogenesis in vitro as well as in vivo. We found that overexpression of Bmi-1 enhanced, whereas knockdown of Bmi-1 diminished, the capability of glioma cells to induce tubule formation and migration of endothelial cells and neovascularization in chicken chorioallantoic membrane. In vivo, Bmi-1 overexpression and knockdown, respectively, promoted and inhibited angiogenesis in orthotopically transplanted human gliomas. Furthermore, NF-κB activity and VEGF-C expression was induced by Bmi-1 overexpression, whereas Bmi-1 knockdown attenuated NF-κB signaling and decreased VEGF-C expression. Additionally suppression of NF-κB activity using a specific chemical inhibitor abrogated the NF-κB activation and the pro-angiogenic activities of glioma cells. Together, our data suggest that Bmi-1 plays an important role in glioma angiogenesis and therefore could represent a potential target for anti-angiogenic therapy against the disease. 相似文献
997.
Peng Zhou Weiyi Xu Xueling Peng Zhenhua Luo Qinghe Xing Xulin Chen Chengqian Hou Weihong Liang Jianwen Zhou Xiaoyan Wu Zhou Songyang Songshan Jiang 《PloS one》2013,8(7)
Animal microRNA (miRNA) target prediction is still a challenge, although many prediction programs have been exploited. MiRNAs exert their function through partially binding the messenger RNAs (mRNAs; likely at 3′ untranslated regions [3′UTRs]), which makes it possible to detect the miRNA-mRNA interactions in vitro by co-transfection of miRNA and a luciferase reporter gene containing the target mRNA fragment into mammalian cells under a dual-luciferase assay system. Here, we constructed a human miRNA expression library and used a dual-luciferase assay system to perform large-scale screens of interactions between miRNAs and the 3′UTRs of seven genes, which included more than 3,000 interactions with triplicate experiments for each interaction. The screening results showed that the 3′UTR of one gene can be targeted by multiple miRNAs. Among the prediction algorithms, a Bayesian phylogenetic miRNA target identification algorithm and a support vector machine (SVM) presented a relatively better performance (27% for EIMMo and 24.7% for miRDB) against the average precision (17.3%) of the nine prediction programs used here. Additionally, we noticed that a relatively high conservation level was shown at the miRNA 3′ end targeted regions, as well as the 5′ end (seed region) binding sites. 相似文献
998.
Penghong Song Wenfeng Song Xiaosun Liu Changhai Jin Haiyang Xie Lin Zhou Biguang Tuo Shusen Zheng 《PloS one》2013,8(4)
The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3
- and Cl- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3
- and Cl- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3
- and Cl- secretions in mice, but forskolin-stimulated HCO3
- and Cl- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα. 相似文献
999.
Caiyun Zhang Xicheng Song Minhui Zhu Song Shi Meng Li Lei Jin Juntian Lang Guojun Li Hongliang Zheng 《PloS one》2013,8(2)
Background
MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.Methods
We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs).Results
Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07–1.79 and OR, 1.27; 95% CI, 1.05–1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29–2.08; OR, 1.39; 95% CI, 1.06–1.82; and OR, 1.41; 95% CI, 1.21–1.65, respectively), European population (OR, 0.58; 95% CI, 0.40–0.84; OR, 0.64; 95% CI, 0.44–0.92; and OR, 0.68; 95% CI, 0.54–0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05–1.47; OR,1.48; 95% CI,1.04–2.12; and OR, 1.22; 95% CI, 1.07–1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model.Conclusion
Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings. 相似文献1000.
Liang Zhou Ning Zhang Wenjie Song Nan You Qingjun Li Wei Sun Yong Zhang Desheng Wang Kefeng Dou 《PloS one》2013,8(2)