Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway

BACKGROUND AND PURPOSE Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS Toluquinol inhibited LEC proliferation,migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependentmanner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by personal funding by FP7-PEOPLE-2013-IEF Marie Curie Postdoctoral Fellowship (MGC). Acknowledged are the supporting grants from the Action de Recherche Concertée (ARC) (Université de Liège), the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS), the Foundation Against Cancer (foundation of public interest), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the Interuniversity Attraction Poles Programme-Belgian Science Policy (all from Belgium) and the Plan National Cancer (« Service Public Federal » from Belgium). Research in the lab of A.R.Q. and M.A.M. was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER)

Pengaruh Pendekatan Saintifik Terhadap Kemampuan Memproduksi Teks Prosedur Kompleks Oleh Siswa Kelas X SMA Negeri 1 Lima Puluh Tahun Pembelajaran 2014/2015

Penelitian ini bertujuan untuk mengetahui pengaruhpendekatansaintifikdalammeningkatkan kemampuan memproduksiteks prosedur kompleks. Populasi dalam penelitian ini adalah seluruh siswa kelas X SMA Negeri 1 Lima Puluh dengan jumlah 250 siswa. Sampel dalam penelitian ini berjumlah 34 siswa yang diambil dengan teknik random sampling. Instrumen yang digunakan untuk menjaring data tes tertulis. Metode yang digunakan dalam penelitian ini adalah metode eksperimen, tepatnya Quasi eksperimen. Pengujian hipotesis dilakukan dengan menggunakan uji “t”.Dari pengolahan data, diperolehnilai rata-rata pre-test = 64,26,standardeviasi = 9,08, digolongkanpadakategorisangatbaik = 2,9%, kategoribaik 17,64%, kategoricukup = 41,17 %, kategorikurang = 20,5% dankategorisangatkurang = 15%. Nilai rata-rata post-test = 76,61, standardeviasi = 10,69 dandikategorikanpadakategorisangatbaik = 22,5%, baik = 42,5%, cukup = 27,5 % dankurang =17,6%. Berdasarkanujinormalitas, hasilpre-testdanpost-testdinyatakanberdistribusi normal. Setelahujinormalitasdanujihomogenitasdilakukan, makadiketahui t0sebesar 5,08. Selanjutnya t0tersebutdikonsultasikandengantabel t padatarafsignifikansi 5% dengandf= N-1, yakni 34-1=33. Dari df 33 diperolehtarafsignifikansi 5% = 2,03. Dengandemikianthitung>ttabel, yakni 5,08 > 2,03 dengandemikianhipotesisalternatif (Ha) diterima.Dengandemikian, dapatdisimpulkanbahwaPendekatanSaintifikberpengaruhpositifterhadapkemampuanmemproduksiteksprosedur komplekspadasiswakelas X SMA Negeri 1 Lima Puluhtahunpembelajaran 2014/2015. Penelitian ini diharapkan dapat berguna bagi para pelaksana dan penyelenggara pendidikan khususnya pada tingkat Sekolah Menengah Atas pada kelas X, guru, kepala sekolah, dan peneliti lainnya

Methods for Agricultural Policy Analysis: An Overview

This article summarizes the articles that have been presented at the Workshop on Methods for Agricultural Policy Analysis held at UP Los Baños on August 13-14, 1985. It has four parts: the farm production/productivity change, the food consumption, the rural/ agricultural households in imperfect market settings and the methodologies for combining partial and general equilibrium framework.economic/development modelling, computable general equilibrium (CGE), agriculture sector

The Effect of Health Education to Community Knowledge and Aedes Aegypti Density in Bayah Subdistrict, Banten Province

Dengue Haemorrhagic Fever (DHF) is a public health problem in Bayah, Banten Province thus, control of mosquitoes breeding sites (CMBS) and health education is necessary. This study aimed to evaluate the effect of health education on people’s level of knowledge on CMBS and the density of Ae. aegypti. This study involved 106 villagers from Bayah in August (pretest) and October (postest) 2009. Data was collected through questionnaires, followed by observation of containers available in the house using single larval method and identified microscopically. Data was analyzed using marginal homogeneity test. The result showed, 64.2% and 1.3% villagers had poor and good knowledge on CMBS. This finding was in accordance to their education level and socio-economic status. After education, there were 14% had good and 54% poor knowledge (p = 0,001). Container index (CI) and house index (HI) were 18% and 52% respectively, suggesting high density of Ae. aegypti in that area. Following health education, CI and HI became 16% and 42% which were still above WHO level of indicator; which gave no significant difference in CI (p = 0,523) and HI (p = 0,174). In conclusion, the level of knowledge increased after health education which was not followed by significant decrease in vector density, suggesting Bayah is still categorized as highly transmitted area of DHF

Kadar Malondialdehid (Mda) Dan Gambaran Histologi Pada Ginjal Tikus Putih (Rattus Norvegicus) Pasca Induksi Cylosporine-a

Cyclosporine-A (CsA) merupakan kelompok obat (immunosuppressant) yang berfungsi menekan respon imun.Namun demikian, penggunaan CsA jangka panjang dapat menimbulkan efek nefrotoksisitas.Penilitian ini bertujuan untuk mengetahui kadar MDA dan gambaran histologi pada ginjal tikus (Rattus norvegicus) pasca induksi Cyclosporine-A (CsA). Pada penelitian ini ginjal yang digunakan berasal dari dua kelompok, yaitu kelompok tikus kontrol dan tikus induksi CsA dengan dosis 3 mg/kg per berat badan tikus. Pengukuran kadar MDA menggunakan spektroftotometri UV-vis dan gambaran histologi menggunakan metode pewarnaan Hematoksilin-Eosin (HE). Hasil perbandingan kadar MDA pada ginjal tikus sehat (1,599±0,328) dan ginjal tikus sakit (5,693±0,243) mengalami peningkatan 56,14%.Pada tikus sakit terdapat banyak rongga sebagai visualisasi terputusnya sel junction (penghubung antar sel) karena adanya peradangan. Terbentuknya rongga atau celah antar sel merupakan akibat dari meningkatnya kadar MDA

Hubungan Peran Keluarga Dengan Kepatuhan Berobat Pasien Hipertensi Di Desa Batu Kecamatan Likupang Selatan Kabupaten Minahasa Utara

: Chronic disease defined as a medical condition or health issue related with the symptoms or defections which are need a long term management. Hypertension become one of the stern diseases and categorize as an illness that might kill someone quietly because commonly the patient do not realize that himself or herself is suffering the hypertension before he or she check the blood pleasure. The purpose of this study was to investigate the correlation between family roles and medical treatment compliance of hypertension patients in Batu South Likupang North Minahasa. The research method used cross sectional analytic survey and chi square test for the statistical test. The population in this study was hypertension patients who attended a medical treatment at the health centre clinic of Batu. This study did in Batu on March 18 to April 18 2015. The sample taken in this research was 64 respondents and used purposive sampling technique. The Questionnaires used as the instruments of this study. The result was p-value = 0.000. In conclusion there is any significant correlation between family roles and the medical treatment compliance of the hypertension patient. Suggestion the result of this study could give more information and knowledge for those who want to do the research related to this study and developed by correlating it with other variables such as self motivation and medical treatment of hypertension patient

Who decides to grow orange sweet potatoes? Bargaining power and adoption of biofortified crops in Uganda.

The goal of the HarvestPlus reaching end users (REU) orange sweet potato (OSP) project is to increase vitamin A intake and improve vitamin status among Vulnerable populations (women and children) in rural Uganda by introducing beta-carotene-rich OSP, as well as related messages concerning agronomy, nutrition, and marketing. Most households obtain planting material for these crops through interaction with other households. This raises a number of important questions about the roles of social interaction, intrahousehold division of labor, and gender in determining the rates at which these biofortified crops are adopted and spread. As part of the Gender, Agriculture, and Assets Project (GAAP), this study examines the effect of women’s bargaining power, as revealed in gender¬‐based patterns of ownership and control of land and assets, on adoption ofOSP and vitamin A intake among children

Bargaining power and biofortification: The role of gender in adoption of orange sweet potato in Uganda

We examine the role of gender in adoption and diffusion of orange sweet potato, a biofortified staple food crop being promoted as a strategy to increase dietary intakes of vitamin A among young children and adult women in Uganda. As an agricultural intervention with nutrition objectives, intrahousehold gender dynamics regarding decisions about crop choice and child feeding practices may play a role in adoption decisions. Also, most households access sweet potato vines through informal exchange, suggesting again that gender dimensions of networks may be important to diffusion of the crop. We use data from an experimental impact evaluation of the introduction of OSP in Uganda to study how female bargaining power, measured by share of land and nonland assets controlled by women, affect adoption and diffusion decisions. We find that the share of assets controlled by women does not affect the probability of adopting OSP at the household level. In examining adoption decisions within households, plots of land exclusively controlled by women are not more likely to contain OSP, but plots under joint control of men and women, in which a woman has primary control over decisionmaking are significantly more likely to contain OSP. Plots exclusively controlled by men are the least likely to contain OSP. Also, we find that the share of nonland assets controlled by women increases dietary intakes of vitamin A, but this measure of female bargaining power does not increase the impact of the OSP project on vitamin A, suggesting that the project had similar impacts across households with different levels of female bargaining power