In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells

<p>Abstract</p> <p>Background</p> <p>LGD1069 (Targretin^®) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes.</p> <p>Methods</p> <p>Human umbilical vein endothelial cells (HUVECs) were used for <it>in vitro </it>study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis <it>in vitro</it>. <it>In vitro </it>adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis.</p> <p>Results</p> <p>Our data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators.</p> <p>Conclusions</p> <p>Our results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy.</p

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study

IntroductionThe efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear.Methods3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer’s tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment.ResultsBased on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs.DiscussionThe use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019)

On multi-copy forwarding protocols for large data chunk dissemination in vehicular sensor networks

Abstract Moving vehicles have been sensing all kinds of data on the road in which multimedia data possesses a large portion. These data is often forwarded to vehicles in a region of interest or the monitoring center in an opportunistic manner. With respect to the large volume content, the storage space of relay vehicles is becoming the bottleneck of achieving higher performance, e.g., a data chunk may be rejected or dropped due to insufficient storage of intermediate vehicles. Thus, previous work that only focuses on the delivery metric without considering the data size is not likely to work efficiently in the proposed scenario. As deploying stationary infrastructures is of very large cost and not feasible everywhere, in this paper, we focus on the inter-vehicle data forwarding problem with storage and communication capacity constraints. First, we considered the situation when the vehicles are distributed sparsely. The multi-copy routing challenge is modeled as a multiple knapsack problem. Then, it is extended to a dense scenario. An optimization to the broadcast data forwarding is investigated. With the real data trace, the experiments show that our scheme achieves better performance than the competitors in terms of delay and delivery ratio. A better balance between duplication and performance is also achieved by the multi-copy algorithm

The Landscape of PDK1 in Breast Cancer

Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize the interaction networks of PDK1. Then, we establish the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More importantly, we sort the current preclinical or clinical trials of PDK1-targeted therapy in BC and find that, even though no selective PDK1 inhibitor is currently available for BC therapy, the combination trials of PDK1-targeted therapy and other agents have provided some benefit. Thus, there is increasing anticipation that PDK1-targeted therapy will have its space in future therapeutic approaches related to BC, and we hope the novel approaches of targeted therapy will be conducive to ameliorating the dismal prognosis of BC patients

Hydrogen substituted graphdiyne as carbon-rich flexible electrode for lithium and sodium ion batteries

Flexible batteries have been used to power wearable smart electronics and implantable medical devices. Here, the authors report a carbon-rich flexible hydrogen substituted graphdiyne electrode exhibiting superior electrochemical performance in lithium and sodium ion batteries

Geographic distribution of the prevalence of infectious corneal blindness.

<p>Geographic distribution of the prevalence of infectious corneal blindness.</p

Demographic characteristics and the prevalence of corneal blindness.

a<p>Comparisons between males and females. Blindness in both eyes, χ² = 2.18, p = 0.14; blindness in one eye, χ² = 3.48, p = 0.06; blindness in at least one eye(total), χ² = 5.25, p = 0.02 (statistically significant difference).</p>b<p>Comparisons between different ages. Blindness in both eyes, χ² = 131.39, p<0.001 (statistically significant difference); blindness in one eye, χ² = 608.80, p<0.001 (statistically significant difference); blindness in at least one eye(total), χ² = 739.70, p <0.001 (statistically significant difference).</p>c<p>Comparisons between different education levels. Blindness in both eyes, χ² = 100.87, p<0.001 (statistically significant difference); blindness in one eye, χ² = 321.00, p<0.001 (statistically significant difference); blindness in at least one eye(total), χ² = 416.79, p≤0.001 (statistically significant difference).</p>d<p>Comparisons between rural and urban areas. Blindness in both eyes, χ² = 12.60, p<0.001 (statistically significant difference); blindness in one eye, χ² = 48.43, p<0.001 (statistically significant difference); blindness in at least one eye(total), χ² = 60.74, p<0.001 (statistically significant difference).</p><p>Demographic characteristics and the prevalence of corneal blindness.</p