Knockdown of LncRNA SBF2-AS1 Inhibited Gastric Cancer Tumorigenesis via the Wnt/LRP5 Signaling Pathway

This investigation aimed to uncover the impact of a long noncoding RNA, SET-binding factor 2 antisense RNA1 (SBF2-AS1) on the malignant progression of gastric cancer (GC) and to further explore its underlying mechanism. SBF2-AS1 expression was quantified by qRT-PCR in GC cell lines and GC tissues. In vitro loss-of-function studies of SBF2-AS1, accompanied by flow cytometry, CCK-8, and cell invasion tests, were applied to elucidate the impact of SBF2-AS1 on the tumor progression of GC cells. Finally, Western blotting and a luciferase assay were used to detect WNT/LRP5 signaling pathway activation. SBF2-AS1 was aberrantly expressed in GC cell lines (p<0.05) and GC tissues (p<0.05). Cell invasive and proliferative capabilities were inhibited via SBF2-AS1 knockdown, resulting in apoptosis of NCI-N87 and MKN74 cells. Additionally, online database analysis uncovered a positive correlation between SBF2-AS1 and the Wnt/LRP5 signaling pathway (p<0.05). SBF2-AS1 knockdown blocked the Wnt/LRP5 signaling pathway, whereas the effects of SBF2-AS1 knockdown on the malignant genotype of MKN74 as well as NCI-N87 cells were partially restored by triggering the Wnt/ LRP5 signaling pathway. High expression of SBF2-AS1 was found in GC, the malignant progression of which was repressed via SBF2-AS1 knockdown by inhibiting the Wnt/LRP5 signaling pathway

Research Progress on Immunomodulatory Activity of Polysaccharides from Blue Foods

With the current over-exploitation of terrestrial resources, multi-dimensional in-depth utilization of aquatic resources has attracted widespread attention. Blue foods including marine animals and algae supply nutrients to 3.2 billion people around the world. Polysaccharides are an important class of nutritional components in “blue foods”, and have various biological activities such as antitumor, anti-inflammatory, and anti-allergic functions. The exertion of these physiological functions is closely related to their immunomodulatory activities. Therefore, this article reviews recent progress on the classification, composition and immunomodulatory activities of polysaccharides in blue foods with a focus on the regulatory effects of polysaccharides in marine mollusks and seaweeds on innate/adaptive immune responses, the antitumor effects of pro-inflammatory polysaccharides, and their role in immune adjuvants, and the role of anti-inflammatory polysaccharides in autoimmune diseases and inflammation in an effort to enrich the understanding of the different immune effects of marine polysaccharides and to provide theoretical support for the development of immunomodulatory functional foods based on polysaccharides from blue foods

The impact of China’s new Environmental Protection Law on corporate environmental investments

As an important lever for China’s green development strategy, whether the new Environmental Protection Law can effectively form investment incentives for enterprises has attracted much attention and is also an important topic that theoretical research urgently needs to explore. This paper utilizes corporate data from non-financial listed companies in Shanghai and Shenzhen A-shares from 2007 to 2018. By adopting a double-difference model, it explores the incentive role and internal mechanism of the new Environmental Protection Law (EPL), implemented in 2015, as an environmental regulation on the environmental protection investment of enterprises, taking the new EPL’s enactment as a quasi-natural experiment. The study revealed a noteworthy and positive impact on motivation, which remained consistent even after various robustness tests. Additionally, the impact of incentives varied depending on the level of competition within the industry, financial constraints, and ownership type of the enterprises. Investigating the mechanism, it has been discovered that the incentive effect advances the environmental investment of firms through diminishing agency costs, enriching the quality of environmental information disclosure, and facilitating government subsidies to enterprises. This study not only verifies, from the factual empirical level, that environmental regulation policies can promote corporate environmental investment but also provides important evidence to support to a certain extent that the implementation of the new EPL can promote enterprises’ environmental governance behaviors. This article reveals the microeconomic effects of the new Environmental Protection Law from the perspective of corporate behavior strategies, and the research conclusions have important reference significance for the construction of national legal systems and the deepening of green development strategies

Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy.

Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi\u27s sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer tethered to the underlying capsid and an outer, flexible tegument layer conforming to the overlying, pleomorphic envelope, consistent with the sequential viral tegumentation process inside host cells. Surprisingly, comparison of the MHV-68 virion and capsid reconstructions shows that the interactions between the capsid and inner tegument proteins are completely different from those observed in alpha and betaherpesviruses. These observations support the notion that the inner layer tegument across different subfamilies of herpesviruses has evolved significantly to confer specific characteristics related to viral-host interactions, in contrast to a highly conserved capsid for genome encapsidation and protection

Isolation and complete genomic characterization of H1N1 subtype swine influenza viruses in southern China through the 2009 pandemic

<p>Abstract</p> <p>Background</p> <p>The swine influenza (SI) is an infectious disease of swine and human. The novel swine-origin influenza A (H1N1) that emerged from April 2009 in Mexico spread rapidly and caused a human pandemic globally. To determine whether the tremendous virus had existed in or transmitted to pigs in southern China, eight H1N1 influenza strains were identified from pigs of Guangdong province during 2008-2009.</p> <p>Results</p> <p>Based on the homology and phylogenetic analyses of the nucleotide sequences of each gene segments, the isolates were confirmed to belong to the classical SI group, with HA, NP and NS most similar to 2009 human-like H1N1 influenza virus lineages. All of the eight strains were low pathogenic influenza viruses, had the same host range, and not sensitive to class of antiviral drugs.</p> <p>Conclusions</p> <p>This study provides the evidence that there is no 2009 H1N1-like virus emerged in southern China, but the importance of swine influenza virus surveillance in China should be given a high priority.</p

cDNA-AFLP analysis reveals differential gene expression in compatible interaction of wheat challenged with Puccinia striiformis f. sp. tritici

<p>Abstract</p> <p>Background</p> <p><it>Puccinia striiformis </it>f. sp. <it>tritici </it>is a fungal pathogen causing stripe rust, one of the most important wheat diseases worldwide. The fungus is strictly biotrophic and thus, completely dependent on living host cells for its reproduction, which makes it difficult to study genes of the pathogen. In spite of its economic importance, little is known about the molecular basis of compatible interaction between the pathogen and wheat host. In this study, we identified wheat and <it>P. striiformis </it>genes associated with the infection process by conducting a large-scale transcriptomic analysis using cDNA-AFLP.</p> <p>Results</p> <p>Of the total 54,912 transcript derived fragments (TDFs) obtained using cDNA-AFLP with 64 primer pairs, 2,306 (4.2%) displayed altered expression patterns after inoculation, of which 966 showed up-regulated and 1,340 down-regulated. 186 TDFs produced reliable sequences after sequencing of 208 TDFs selected, of which 74 (40%) had known functions through BLAST searching the GenBank database. Majority of the latter group had predicted gene products involved in energy (13%), signal transduction (5.4%), disease/defence (5.9%) and metabolism (5% of the sequenced TDFs). BLAST searching of the wheat stem rust fungus genome database identified 18 TDFs possibly from the stripe rust pathogen, of which 9 were validated of the pathogen origin using PCR-based assays followed by sequencing confirmation. Of the 186 reliable TDFs, 29 homologous to genes known to play a role in disease/defense, signal transduction or uncharacterized genes were further selected for validation of cDNA-AFLP expression patterns using qRT-PCR analyses. Results confirmed the altered expression patterns of 28 (96.5%) genes revealed by the cDNA-AFLP technique.</p> <p>Conclusion</p> <p>The results show that cDNA-AFLP is a reliable technique for studying expression patterns of genes involved in the wheat-stripe rust interactions. Genes involved in compatible interactions between wheat and the stripe rust pathogen were identified and their expression patterns were determined. The present study should be helpful in elucidating the molecular basis of the infection process, and identifying genes that can be targeted for inhibiting the growth and reproduction of the pathogen. Moreover, this study can also be used to elucidate the defence responses of the genes that were of plant origin.</p

Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc. METHODS: Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-β1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student’s t-tests were used to determine the significance of the results. RESULTS: Bleomycin-induced mice, SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-β1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-β1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment. CONCLUSIONS: Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-β pathway and constitutively activated in the progression of SSc

Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients

Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) among Chinese breast cancer patients.Methods: Three randomized, open-label, two-period crossover bioequivalence studies were conducted with albumin-bound paclitaxel. Each subject received a single dose of 260 mg/m2 albumin-bound paclitaxel [sponsor 1 (QL, light food), sponsor 2 (HR, fasting), sponsor 3 (ZDTQ, light food); test] or Abraxane® (reference) and was monitored for 72 h. Serum concentrations of total paclitaxel and unbound paclitaxel were measured using liquid chromatography/mass spectrometry (LC/MS), and appropriate pharmacokinetic parameters were determined by non-compartmental methods. Safety assessments included adverse events, hematology and biochemistry tests.Results: The bioequivalence analyses of the QL, HR, and ZDTQ products included 24, 23, and 24 patients, respectively. The mean t1/2 was 20.61–27.31 h for total paclitaxel. Food intake did not affect the pharmacokinetics of paclitaxel. From the comparison of total paclitaxel and unbound paclitaxel, the 90% confidence intervals (CIs) for the ratios of Cmax, AUC0−t, and AUC0−∞ were within 80.00–125.00%. The intra-subject variability ranged from 6.4–11% to 9.85–15.87% for total paclitaxel and unbound paclitaxel, respectively. Almost all subjects in the test and Abraxane® (reference) groups experienced mild or moderate adverse events. No fatal AEs or study drug injection site reactions related to these drugs were observed.Conclusion: Albumin-bound paclitaxel (QL, HR or ZDTQ; test products) showed bioequivalence to Abraxane® (reference) with lower intra-subject variability, which was less than 16% in all cases, and was well-tolerated in Chinese breast cancer patients. Twenty-two patients are enough for an albumin-bound paclitaxel bioequivalence study

Enhancement of Canonical Wnt/β-Catenin Signaling Activity by HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells

BACKGROUND: The Hepatitis C virus (HCV) core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC), but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells. METHODOLOGY: Wnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay. PRINCIPAL FINDINGS: HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC. CONCLUSIONS/SIGNIFICANCE: HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis