Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.

Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

Plants as Factories for Human Pharmaceuticals: Applications and Challenges.

Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

miR-133b has protective effect on rats with acute lung injury caused by severe acute pancreatitis through targeting sp1 gene.

OBJECTIVE: We aimed to investigate the regulatory mechanism of miR-133b and Sp1 in rats with severe acute pancreatitis complicated by acute lung injury. METHODS: The rats were divided into normal, NC, model, si-Sp1, miR-133b mimic, miR-133b inhibitor, and miR-133b inhibitor + si-Sp1 group and received different treatments. RESULTS: Compared with normal mice, model mice had a lower miR-133b expression, but higher levels of Sp1 expression, W/D of lung tissue, myeloperoxidase activities, and higher levels of interleukin(IL)-6, tumor necrosis factor (TNF)-α and IL-1ß, cell apoptosis rate and Notch-1, and Hes-1, nuclear factor (NF)-κB P65 expressions in lung tissue. Compared with model mice, mice in the si-Sp1 group and the miR-133b mimic group had significantly lower W/D of lung tissue, myeloperoxidase activities, lower levels of IL-6, TNF-α and IL-1ß, cell apoptosis rate and Notch-1, Hes-1, and NF-κB P65 expressions in lung tissue. Mice treated by miR-133b inhibitor showed opposite results in all above parameters, which were similar with those in the model group. The negative effects of miR-133b inhibitor could be reversed by the combination use of si-Sp1. CONCLUSION: Overexpression of miR-133b could inhibit Sp1 expression, thereby improving severe acute pancreatitis in rats and playing a protective role in acute lung injury.

ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis.

Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Here, we report that the expression of lncRNA SNHG22 (small nucleolar RNA host gene 22) was significantly increased in GC (Gastric Cancer) tissues and cells, which confers poor prognosis of patients. Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4 (ETS transcription factor ELK4), could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 (notch receptor 1) expression. Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

MicroRNA-421 improves ischemia/reperfusion injury via regulation toll-like receptor 4 pathway.

OBJECTIVES: The objective was to investigate the effects of microRNA-421 against myocardial ischemia/reperfusion injury in C57BL/6 mice. METHODS: Male C57BL/6 mice (n = 27) were randomly divided into three groups: normal control (NC) group (sham-treated); I/R model group, which underwent the I30min/R24h model (ischemia for 30 minutes followed by reperfusion for 24 hours); and the miRNA group, which were injected with miR-421. Pathology was assessed by hematoxylin and eosin staining and myocardial infarct size was measured by triphenyltetrazolium chloride staining. The apoptosis rate was measured by TUNEL assay, and relative expression of toll-like receptor-4 (TLR4), Janus kinase 2 (JAK2), and signal transducer and activator of translation 3 (STAT3) was evaluated by immunohistochemistry. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and high mobility group protein B1 (HMGB1) serum concentrations were measured by ELISA. RESULTS: Compared with the NC group, in the model group, the myocardial infarction was large; inflammatory cell infiltration was severe; apoptosis was enhanced; expression of TLR4, JAK2, and STAT3 was increased; and serum concentrations of IL-6, TNF-α, IL-10, and HMGB1 were significantly increased. In the miRNA group, the ischemia/reperfusion injury was significantly improved. CONCLUSIONS: Overexpression of miRNA-421 could reduce ischemia/reperfusion inflammatory response, perhaps via inactivation of TLR4, JAK2, and STAT3.

Association between nut consumption and coronary heart disease: a meta-analysis.

OBJECTIVES: Epidemiological studies evaluating the association of nut consumption with coronary heart disease (CHD) risk have produced inconsistent results. The current study aimed to assess the CHD risk for the highest versus the lowest categories of nut consumption, the dose-response association of CHD for every 1 serving/week increment in nut consumption, and the heterogeneity among studies and publication bias. METHODS: Pertinent studies were identified by a search in PubMed and Web of Knowledge up to January 2014. A random-effect model was used to combine the results. The dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Ten articles with 14 studies including 6302 CHD cases were included in this meta-analysis. Pooled results suggested that highest nut consumption amount versus lowest amount was associated significantly with a reduced risk of CHD [summary relative risk (RR)=0.681, 95% confidence interval (CI)=0.592-0.783, I(2)=62.7%], especially among USA (summary RR=0.671, 95% CI=0.591-0.761) and prospective studies (summary RR=0.660, 95% CI=0.581-0.748). A linear dose-response relationship was found, and the risk of CHD decreased by 10% for every 1 serving/week increase intake of nut (summary RR=0.90, 95% CI=0.87-0.94) No publication bias was found. CONCLUSION: Our analysis suggested that higher nut consumption might have a protective effect on CHD risk, especially in the USA, which needs to be confirmed.