Complete mitochondrial genome and phylogenetic analysis of Danio roseus (Teleostei, Cypriniformes, Danionidae).

Danio roseus, collected from Gadu River in Yingjiang area, Yunnan Province, China, had been sequenced on Illumina HiSeq platform with 16523 bp in length, which included 37 genes encoding 13 proteins-coding genes (PCGs), 22 tRNAs, 2 rRNAs and a displacement loop region. The proportion of nucleotides in mitochondrial genome was T (28.7%), C (23.2%), A (32.3%), G (15.8%) with an AT bias of 61%. Maximum-Likelihood phylogenetic tree was reconstructed using concatenated mitochondrial protein-coding genes of D. roseus and other 12 fishes. The result of phylogenetic analysis supported the consanguineous relationship among D. roseus, D. rerio, D. nigrofasciatus and D. dangila.

KyoT2 downregulates airway remodeling in asthma.

The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

Profibrotic effect of miR-33a with Akt activation in hepatic stellate cells.

MicroRNAs (miRNAs) attract more attention in the pathophysiology of liver fibrosis and miR-33a has been previously demonstrated as involved in the regulation of cholesterol and lipid metabolism. Transforming growth factor-beta1 (TGF-ß1) is generally accepted to be the main stimulating factor in the hepatic stellate cells (HSCs) activation, which plays an important role in hepatic fibrosis. However, the involvement and underlying mechanism of miR-33a and its role in TGF-ß1-induced hepatic fibrogenesis remains unknown. Here, we investigate the role of miR-33a in the activation of immortalized human HSCs, Lx-2 cells. Our findings have shown that the expression of miR-33a with its host gene sterol regulatory element-binding protein 2 (SREBP2) was more highly expressed in activation of Lx-2 cells than in quiescent cells. The expression of miR-33a on TGF-ß1-induced HSCs activation may be modulated via the activation of PI3K/Akt pathway. In addition, miR-33a significantly correlated with TGF-ß1-induced expression of α1 (I) collagen (Col1A1) and α-SMA in HSCs. Bioinformatics analyses predict that peroxisome proliferator activated receptor-alpha (PPAR-α) is the potential target of miR-33a. We further found that anti-miR-33a significantly increases target gene PPAR-α mRNA and protein level, suggesting that miR-33a involved in HSCs function might be modulated by targeting PPAR-α. Finally, our results indicate that the expression of miR-33a increased with the progression of liver fibrosis. These results suggested that anti-miR-33a inhibit activation and extracellular matrix production, at least in part, via the activation of PI3K/Akt pathway and PPAR-α and anti sense of miR-33a may be a novel potential therapeutic approach for treating hepatic fibrosis in the future.

The bone morphogenetic protein antagonist Gremlin is overexpressed in human malignant mesothelioma.

Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family and its antagonistic effect is likely through direct binding to BMP proteins. As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body patterning and tissue differentiation. Recent studies have shown a deregulation of Gremlin in several types of human cancers. However, the role of Gremlin in human malignant mesothelioma (MM) is still unknown. In this study, we investigated the expression of Gremlin in human MM. We found that Gremlin mRNA and protein were both overexpressed in the majority of primary MM tissue samples that we examined. We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell lines. Consistently, we found that the Gremlin promoter activity was significantly elevated in those MM cell lines expressing the Gremlin gene. On the other hand, no activity of the Gremlin promoter was detected in the two MM cell lines lacking Gremlin expression. Moreover, to examine the functional significance of the Gremlin overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell lines expressing Gremlin and found that inhibition of Gremlin expression significantly suppressed proliferation of those MM cells. Taken together, our results suggest that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation of Gremlin may play a critical role in the tumorigenesis of human MM.

[Correlation between expression of excision repair cross-complementing 1 and cisplatin sensitivity in non-small cell lung cancer].

OBJECTIVE: To investigate the correlation between excision repair cross-complementing 1 (ERCC1) expression and cisplatin sensitivity in non-small cell lung cancer (NSCLC). METHODS: A total of 168 NSCLC patients were selected from our hospital from January 2005 to December 2007. The expression of ERCC1 protein was analyzed by immunohistochemistry and ERCC1 mRNA tested by RT-PCR. Analyses were performed to determine the correlation between expression of ERCC1 and chemotherapeutic sensitivity in NSCLC. RESULTS: A positive expression of ERCC1 protein was found in 99 (58.93%) patients. The expression of ERCC1 had no correlation with gender, age, stage and pathological types (P > 0.05). Among all patients, 133 were followed up for about 3-5 years and 91 cases belonged to the responding group. Three cases with stage Ia-Ib underwent only operation without chemotherapy. And 76 (58.46%) patients were positive for ERCC1 expression in 130 cases. In the responding group, 38 (43.18%) cases had a positive expression of ERCC1 and 50 (56.82%)cases a negative expression of ERCC1. In the non-responding group, 37 (88.10%)cases had a positive expression of ERCC1 and 5 (11.90%) cases a negative expression of ERCC1. The expression of ERCC1 decreased in the responding group versus the non-responding group (χ(2) = 23.50, P < 0.01). The expressions of ERCC1 mRNA were (0.624 ± 0.275) and (2.758 ± 0.771) in the responding and non-responding groups respectively (t = 11.54, P = 0.013). CONCLUSION: An elevated expression of ERCC1 is an important factor for cisplatin insensitivity in NSCLC. It may provide an useful reference for designing individualized chemotherapeutic regimens for NSCLC patients.

Outcome following surgery for squamous cell carcinoma of the oesophagus.

INTRODUCTION: This study was undertaken to determine the outcomes of patients treated for squamous cell carcinoma (SCC) of the oesophagus. METHODS: The study group consisted of 61 patients (median age: 64 years) with invasive SCC of the oesophagus who underwent resection between 1987 and 2007 in Adelaide, South Australia. Thirty-two (52%) were female. Survival data were available for all patients. The log rank test was performed to identify prognostic factors for survival. RESULTS: The 5-year overall survival rate was 33% (median: 24 months). Of 61 patients, 42 (69%) received neoadjuvant therapy prior to surgery. The overall resection rate was 95%. Significant post-operative morbidity occurred in 47%, and the in-hospital mortality was 5% (30-day mortality: 3%). No overall survival benefit was seen in patients undergoing neoadjuvant therapy prior to surgical resection. However, patients who had a complete pathological response to neoadjuvant therapy had a better 5-year survival than patients who did not receive neoadjuvant therapy: 47% versus 30%, respectively. CONCLUSIONS: Oesophagectomy following neoadjuvant therapy for SCC of the oesophagus can be performed with low perioperative mortality. A complete response to neoadjuvant therapy was followed by an improved survival outcome.

[Preliminary investigation of the molecular mechanisms of imipenem-resistance in clinical isolates of Acinetobacter baumannii in Xi'an].

OBJECTIVE: To investigate the molecular mechanism of carbapenem resistance in the clinical isolates of Acinetobacter baumannii from Xi'an and their profile of carbapenemase production. METHODS: A total of 146 Acinetobacter baumannii strains were isolated from 6 general hospitals in Xi'an. Antimicrobial susceptibility test was performed for all the strains, followed by detection of imipenem resistance using E-test for metallo-beta-lactamase (MBL) and NaCl inhibition test for OXA type carbapenemase. Bla(OXA-23)and bla(OXA-58) were amplified by PCR, and the positive products were sequenced. RESULTS: From the collected strains, 15 non-repetitive imipenem-resistant Acinetobacter baumannii strains were identified, among which 14 yielded negative results in E-test for MBL production. All the resistant strains showed increased sensitivity to imipenem after NaCl inhibition, suggesting the presence of carbapenemase production. Eleven of the strains harbored OXA -23 type gene and 1 harbored OXA -58 type gene. The concordance rate of the results by NaCl inhibition test and PCR was 85.7%. CONCLUSIONS: Production of OXA-type carbapenemase is the most important reason for carbapenem resistance in Acinetobacter baumannii in Xi'an. The OXA-58 type gene is a novel carbapenemase genotype in China. NaCl inhibition test is a convenient and cost-effective method for detecting carbapenemase in Acinetobacter baumannii.