Preventive and (Neo)Adjuvant Therapeutic Effects of Metformin on Cancer

Metformin, the first-line antidiabetic drug, has become an attractive candidate in cancer therapy since retrospective clinical investigations reported that patients with type 2 diabetes receiving metformin had lower incidence of cancer than those with other glucose lowering drugs. In line with this, preclinical studies have demonstrated that the antitumor activity of metformin could proceed through several mechanisms. Thus far, metformin has been used in cancer prevention with reduced risk as consequence and treatment of various cancers as an adjuvant or neoadjuvant drug. Thus, existing data support the beneficial effects of metformin on many types of cancers such as reducing metastasis and mortality and improving pathological responses and survival rates. However, some reports do not support this and even show adverse effects. The discrepancy may be attributed to expression levels of its transporters or genetic background. Hence, this chapter briefly reviews information on the mechanism of metformin action and summarizes both completed and ongoing clinical trials in an attempt to evaluate the value of metformin in prevention and treatment of various cancer types

A Method for Learning a Petri Net Model Based on Region Theory

The deployment of robots in real life applications is growing. For better control and analysis of robots, modeling and learning are the hot topics in the field. This paper proposes a method for learning a Petri net model from the limited attempts of robots. The method can supplement the information getting from robot system and then derive an accurate Petri net based on region theory accordingly. We take the building block world as an example to illustrate the presented method and prove the rationality of the method by two theorems. Moreover, the method described in this paper has been implemented by a program and tested on a set of examples. The results of experiments show that our algorithm is feasible and effective

Associations Between Home Dampness-related Indicators and Eczema among Preschool Children in Shanghai, China

AbstractIn recent years, prevalence of eczema has been increasing among preschool children in China. It's urgent to find associated factors. On basis of 13,335 questionnaires from parents or guardians for 4-6 year-old children (response rate 85.3%) in a cross-sectional study from April 2011 to April 2012 in Shanghai, the associations between home dampness related indicators and the prevalence of childhood eczema was investigated. There were 7.8%, 15.3%, 42.1%, 55.7%, and 30.7% of the surveyed residences who had visible mold spots, visible damp stains, damp clothing and/or bedding, water damage, condensation on window in winter, and moldy odor (six home dampness-related indicators), respectively. The prevalence of eczema (ever) and eczema (in the past 12 months) was 22.9% and 13.2%, respectively. These home dampness indicators had significant and strong associations with the increased risk of childhood eczema. With regard to the same indicators, the increased risk of eczema in girls was higher than in boys. Total numbers of home dampness-related indicators had notable dose-response relationships with the prevalence of childhood eczema. In conclusion, home dampness-related exposures are strong risk factors for childhood eczema

Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis

It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA). The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs) from RA. Exposure of RA FLSs to TNF-α (10 ng/ml) led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by a γ-secretase inhibitor (DAPT) inhibited IL-6 secretion of RA FLSs in response to TNF-α while treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-α stimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy

Circular RNA circHIPK3 Promotes the Proliferation and Differentiation of Chicken Myoblast Cells by Sponging miR-30a-3p

Circular RNAs and microRNAs widely exist in various species and play crucial roles in multiple biological processes. It is essential to study their roles in myogenesis. In our previous sequencing data, both miR-30a-3p and circular HIPK3 (circHIPK3) RNA, which are produced by the third exon of the HIPK3 gene, were differentially expressed among chicken skeletal muscles at 11 embryo age (E11), 16 embryo age (E16), and 1-day post-hatch (P1). Here, we investigated their potential roles in myogenesis. Proliferation experiment showed that miR-30a-3p could inhibit the proliferation of myoblast. Through dual-luciferase assay and Myosin heavy chain (MYHC) immunofluorescence, we found that miR-30a-3p could inhibit the differentiation of myoblast by binding to Myocyte Enhancer Factor 2 C (MEF2C), which could promote the differentiation of myoblast. Then, we found that circHIPK3 could act as a sponge of miR-30a-3p and exerted a counteractive effect of miR-30a-3p by promoting the proliferation and differentiation of myoblasts. Taking together, our data suggested that circHIPK3 could promote the chicken embryonic skeletal muscle development by sponging miR-30a-3p

Gga-miR-205a Affecting Myoblast Proliferation and Differentiation by Targeting CDH11

Non-coding RNAs especially miRNAs have been found to play important roles during skeletal muscle development. Our previous RNA-Seq performed on breast muscle tissue from 7 weeks old Recessive White Rock and Xinhua Chicken and leg muscle tissue from female Xinghua Chicken at three development time points (11 embryo age, 16 embryo age, and 1 day post hatch) (accession number GSE62971 and GSE89355, respectively) showed that miR-205a and CDH11 were differentially expressed genes. In this study, we found that overexpression of CDH11 significantly facilitated Quail muscle clone (QM7) and chicken primary myoblast (CPM) proliferation and hampered CPM differentiation. MiR-205a can directly binding to the 3′UTR of CDH11 and the overexpression of miR-205a could inhibit both cell lines (QM7) and CPM proliferation, at the meantime promote the differentiation of myoblasts. The Dual-Luciferase Reporter Assay results and qRT-PCR results showed that myogenin (MyoG) could regulate the expression of miR-205a by binding to the active region of miR-205a. Altogether our data suggest that MyoG could stimulate miR-205a expression to suppress CDH11, which promotes myoblasts proliferation while represses the differentiation

An AT-hook gene is required for palea formation and floral organ number control in rice

AbstractGrasses have highly specialized flowers and their outer floral organ identity remains unclear. In this study, we identified and characterized rice mutants that specifically disrupted the development of palea, one of the outer whorl floral organs. The depressed palea1 (dp1) mutants show a primary defect in the main structure of palea, implying that palea is a fusion between the main structure and marginal tissues on both sides. The sterile lemma at the palea side is occasionally elongated in dp1 mutants. In addition, we found a floral organ number increase in dp1 mutants at low penetration. Both the sterile lemma elongation and the floral organ number increase phenotype are enhanced by the mutation of an independent gene SMALL DEGENERATIVE PALEA1 (SDP1), whose single mutation causes reduced palea size. E function and presumable A function floral homeotic genes were found suppressed in the dp1–2 mutant. We identified the DP1 gene by map-based cloning and found it encodes a nuclear-localized AT-hook DNA binding protein, suggesting a grass-specific role of chromatin architecture modification in flower development. The DP1 enhancer SDP1 was also positional cloned, and was found identical to the recently reported RETARDED PALEA1 (REP1) gene encoding a TCP family transcription factor. We further found that SDP1/REP1 is downstreamly regulated by DP1

Enhanced HMGB1 Expression May Contribute to Th17 Cells Activation in Rheumatoid Arthritis

Rheumatoid arthritis(RA) is a common autoimmune disease associated with Th17 cells, but what about the effect of high-mobility group box chromosomal protein 1 (HMGB1) and the relationship between Th17-associated factors and HMGB1 in RA remains unknown. In the present study, we investigated the mRNA levels of HMGB1, RORγt, and IL-17 in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by quantitative real-time PCR (RT-qPCR), and the concentrations of HMGB1, IL-17, and IL-23 in plasma were detected by ELISA. And then, the effect of HMGB1 on Th17 cells differentiation was analyzed in vitro. Our clinical studies showed that the mRNAs of HMGB1, RORγt, and IL-17 in patients were higher than that in health control (P < 0.05), especially in active RA patients (P < 0.05). The plasma HMGB1, IL-17, and IL-23 in RA patients were also higher than that in health control (P < 0.05); there was a positive correlation between the expression levels of HMGB1 and the amount of CRP, ERS, and RF in plasma. In vitro, the IL-17-produced CD4+T cells were increased with 100 ng/mL rHMGB1 for 12h, which indicated that the increased HMGB1 might contribute to Th17 cells activation in RA patients