Tiotropium resulted in a higher FEV than placebo at 24 months and ameliorated the annual decline in the FEV after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Little is known about the functions of Toll-like receptor 2 (TLR2) and TLR4 in innate/acquired responses to Schistosoma japonicum. Through in vivo study, the contributions of TLR2 and TLR4 to host immune responses during S. japonicum infection were investigated. Early infection experiments showed higher protein and mRNA levels of IL-12, IFN-γ and IL-4 in dermal tissues and retroauricular draining lymph nodes respectively in TLR2(-/-) mice on day four post-infection and opposite changes in TLR4(-/-) mice. In the acute infection with S. japonicum for 6 weeks, TLR2(-/-) mice manifested lower egg burden as well as the enhancement of T cell activation and upregulated expression of some cytotoxic genes, as assayed by Th1/Th2 cytokine secretion and DNA microarray analysis. Also, the opposite parasitological and immunological effects were observed in TLR4(-/-) mice. These results demonstrate that during S. japonicum infection, TLR2 and TLR4 might direct distinct adaptive immune responses since the early stage, which may lead to different infection outcomes.

Background Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. Methods In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. Results LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. Conclusions The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.

Background Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene ( CDC45 ) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. Material/Methods In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. Results CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45 . NUDT1 , E2F1 , CCNE2 , MCM5 , and CENPM were identified as the most significantly co-expressed genes. Conclusions CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1 , E2F1 , CCNE2 , MCM5 , and CENPM .