Ultrasound-targeted microbubble destruction enhances AAV mediated gene transfection: human RPE cells in vitro and the rat retina in vivo

The present study was performed to investigate the efficacy and safety of Ultrasound-targeted microbubble destruction (UTMD) mediated rAAV2-EGFP to cultured human retinal pigment epithelium (RPE) cells _in vitro_ and the rat retina _in vivo_. _In vitro_ study, cultured human RPE cells were exposed to US under different conditions with or without microbubbles. Furthermore, the effect of UTMD to rAAV2-EGFP itself and the cells were evaluated. _In vivo_ study, gene transfer was examined by injecting rAAV2-EGFP into the subretinal space of the rats with or without microbubbles and then exposed to US. We investigated EGFP expression _in vivo_ via stereomicroscopy and performed quantitative analysis by Axiovision 3.1 software. HE staining and frozen sections were used to observe tissue damage and location of EGFP gene expression. _In vitro_ study, the transfection efficiency of rAAV2-EGFP increased 74.85% under the optimal UTMD conditions. Furthermore, there was almost no cytotoxicity to the cells and rAAV2-EGFP itself. _In vivo_ study, UTMD could be used safely to enhance and accelerate transgene expression of the retina. Fluorescence expression was mainly located in the layer of retina. UTMD is a promising method for gene delivery to the retina

Collaborative mechanism on profit allotment and public health for a sustainable supply chain

This paper explores the collaborative mechanism that motivates supply chain firms to collectively invest in environmental technology and produce environmental friendly products (EFPs) to reduce pollutant emissions and negative impacts on environment and public health. Our paper investigates how such firms can achieve the balance between economic feasibility and environmental and social sustainability under multiple sustainable constraints in terms of the triple bottom line dimensions. The work also describes the impacts of interrelated multiple sustainable constraints on optimal policy for the supply chain transfer price and profit allotment decisions. Our findings suggest that government intervention plays a dominant role in governing the supply chain firms’ behaviors in the context of environmental and public health sustainability. The profit allotment is determined through the process of negotiation of the transfer price interrelated with the government subsidy sharing between the supply chain firms

Universal RNA editing in a human liver at the fetal stage

It is known that RNA editing occurs in human cells, which can change the information transmission from DNA to RNA and proteins. Most previous studies have focused on editing of the mRNAs. Here we reported that several kinds of RNAs, including miRNA, rRNA, mRNA, miscRNA and unknown RNA, exhibited base editing in a human fetal liver. Several editing types are displayed. Our data reveals that RNA editing may occur in different species of RNAs.This study was supported by the Huazhong University of Science and Technology (2010MS034).Peer Reviewe

Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages

Background Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood. Methodology and Principal Findings In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB. Conclusion and Significance Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases

MicroRNA-451 suppresses tumor cell growth by down-regulating IL6R gene expression

The miR-451 was found to be frequently down-regulated in tumors, indicating that miR-451 could play an important role in carcinogenesis. This study uncovered the mechanism by which the miR-451 functions as a tumor suppressor. The target genes of miR-451 were determined using target gene prediction softwares. Then the miR-451 mimics were introduced into RKO and Hela cells respectively. The proliferation and invasion of cells were monitored by MTT, cell cycle and in vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA technologies. The mRNA and protein levels of IL6R gene were found to be down-regulated in the RKO and Hela cells transfected with miR-451 mimics. Consequently, the cell proliferation was inhibited. Also, the invasion of RKO cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected with miR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. All these results were validated by IL6R siRNA experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a tumor suppressor, probably by targeting the IL6R pathway.This project was supported by the Huazhong University of Science and Technology (2010MS034 and HF-09-37-2011-510).Ritrýnt tímaritPeer Reviewe

Association of blood pressure with development of metabolic syndrome components: a five-year retrospective cohort study in Beijing

Background: Raised blood pressure (BP) is associated with the incidence of metabolic syndrome (MetS). It is unknown if subjects with different BP levels may develop certain components of MetS over time. We investigated the incidence of MetS relative to different levels of BP over a 5-year period in a Chinese population in Tongren Hospital, Beijing. Methods: During the period of 2006–2011, we recruited 2,781 participants with no MetS, or self-reported type 2 diabetes, dyslipidemia, hypertension, or cardiovascular disease at baseline. Association rule was used to identify the transitions of MetS components over time. Results: The incidence of MetS at follow-up was 9.74% for men and 3.21% for women in the group with optimal BP; 10.29% and 7.22%, respectively, in the group with normal BP; 10.49% and 10.84%, respectively, in the group with high-normal BP; and 14.48% and 23.21%, respectively in the group with high BP. The most common transition was from healthy to healthy in the groups with optimal or normal BP (17.9–49.3%), whereas in the high-normal BP group, 16.9-22.1% of subjects with raised BP returned to healthy status or stayed unchanged, while 13.8-21.4% of people with high BP tended to develop raised fasting glucose levels. Conclusions: The incidence of MetS increased in parallel with the increase in BP. People with optimal and normal BP levels were less susceptible to developing MetS over time, whereas abnormal BP seemed to be a pre-existing phase of MetS. High-normal BP was a crucial status for MetS prevention