Angiopoietin decoy secreted at tumor site impairs tumor growth and metastases by inducing local inflammation and altering neoangiogenesis

The extracellular domain of the receptor tyrosine kinase Tie2/TEK (exTEK) has been used as an angiopoietin decoy to study the role of angiopoietins in the tumor-host interactions, using a syngeneic model of experimental metastases and subcutaneous tumor. Soluble exTEK secreted by transfected tumor cells inhibited HUVECs from forming tubes in Matrigel. ExTEK-transfected C26 colon carcinoma and TS/A mammary tumor cells displayed reduced growth rate when injected subcutaneously, and reduced ability to form experimental metastases when injected intravenously. Immunohistochemical analysis of tumors and metastases showed increased leukocytes infiltration and signs of inflammation in exTEK-secreting compared to parental tumor, as well as impairment in neo-vessel growth and organization. However, while neoangiogenesis eventually rescued in the subcutis, it failed to organize in the experimental metastases of exTEK-secreting tumor, contributing to the hampering of metastatic growth and to increased mice survival. The reactive infiltrate of C26TEK contained a different percentage of leukocytes and was responsible for the tumor inhibition. In fact, leukopenia induced by gamma-irradiation of recipient mice or injection into interferon gamma (IFN-gamma) gene knockout (GKO) mice resulted in reduced mouse survival and an increased number of lung metastases. On the other hand, interleukin (IL)-12 treatment prolonged the survival of mice bearing subcutaneous C26TEK but not of those bearing lung metastases, suggesting that IL-12 could exert further antiangiogenic effects at the site where the tumor can restore neoangiogenesis. These results show in vivo that reduced angiopoietin availability at the tumor site induces a local inflammatory response and impairment of neoangiogenesis which act synergistically to limit tumor growth and metastasis

Response-Time Analysis of Conditional DAG Tasks in Multiprocessor Systems

Different task models have been proposed to represent the parallel structure of real-time tasks executing on manycore platforms: fork/join, synchronous parallel, DAG-based, etc. Despite different schedulability tests and resource augmentation bounds are available for these task systems, we experience difficulties in applying such results to real application scenarios, where the execution flow of parallel tasks is characterized by multiple (and nested) conditional structures. When a conditional branch drives the number and size of sub-jobs to spawn, it is hard to decide which execution path to select for modeling the worst-case scenario. To circumvent this problem, we integrate control flow information in the task model, considering conditional parallel tasks (cp-tasks) represented by DAGs composed of both precedence and conditional edges. For this task model, we identify meaningful parameters that characterize the schedulability of the system, and derive efficient algorithms to compute them. A response time analysis based on these parameters is then presented for different scheduling policies. A set of simulations shows that the proposed approach allows efficiently checking the schedulability of the addressed systems, and that it significantly tightens the schedulability analysis of non-conditional (e.g., Classic DAG) tasks over existing approaches

Tuning Design Parameters of ICAM-1-Targeted 3DNA Nanocarriers to Optimize Pulmonary Targeting Depending on Drug Type

3DNA holds promise as a carrier for drugs that can be intercalated into its core or linked to surface arms. Coupling 3DNA to an antibody targeting intercellular adhesion molecule 1 (ICAM-1) results in high lung-specific biodistributions in vivo. While the role of individual parameters on ICAM-1 targeting has been studied for other nanocarriers, it has never been examined for 3DNA or in a manner capable of revealing the hierarchic interplay among said parameters. In this study, we used 2-layer vs. 4-layer anti-ICAM 3DNA and radiotracing to examine biodistribution in mice. We found that, below saturating conditions and within the ranges tested, the density of targeting antibodies on 3DNA is the most relevant parameter driving lung targeting over liver clearance, compared to the number of antibodies per carrier, total antibody dose, 3DNA dose, 3DNA size, or the administered concentration, which influenced the dose in organs but not the lung specific-over-liver clearance ratio. Data predicts that lung-specific delivery of intercalating (core loaded) drugs can be tuned using this biodistribution pattern, while that of arm-linked (surface loaded) drugs requires a careful parametric balance because increasing anti-ICAM density reduces the number of 3DNA arms available for drug loading

EFEKTIVITAS LAMA PERENDAMAN TELUR IKAN LELE SANGKURIANG (Clarias gariepinus) YANG TERBUAHI PADA EKSTRAK DAUN PEPAYA TERHADAP DAYA TETAS TELUR

Enzim papain yang terdapat pada ekstrak daun pepaya dapat mengurai protein pada lapisan lendir telur ikan dan berfungsi mencegah tumbuhnya suatu penyakit atau jamur yang dapat menyebabkan rendahnya daya tetas telur. Penelitian ini bertujuan untuk mengetahui efektivitas lama perendaman telur ikan lele sangkuriang (Clarias gariepinus) yang terbuahi pada ekstrak daun pepaya terhadap daya tetas telur. Penelitian ini dilaksanakan di Balai Perikanan Budidaya Air Tawar (BPBAT) Mandiangin Kalimantan Selatan pada tanggal 14-21 Februari 2023. Metode yang digunakan dalam penelitian ini adalah Rancangan Acak Lengkap dengan 4 perlakuan dan 3 ulangan. Perlakuan A (Lama perendaman selama 5 menit/ 4000 ppm), Perlakuan B (Lama perendaman selama 10 menit/ 4000 ppm), Perlakuan C (Lama perendaman selama 15 menit/ 4000 ppm), dan Perlakuan D (Kontrol atau tanpa dilakukan perendaman dengan larutan daun pepaya). Hasil penelitian ini menunjukkan bahwa perlakuan C memperoleh hasil terbaik dengan rata-rata waktu perkembangan embriogenesis pada fase blastula yaitu 0,7 jam, pada fase gastrula yaitu 1,5 jam, persentase daya tetas telur mencapai 86,3%, persentase abnormalitas pro-larva sebesar 0%, persentase kelangsungan hidup sebesar 92,3%. Dari hasil penelitian dapat disimpulkan bahwa lama perendaman telur ikan Lele Sangkuriang yang terbuahi berpengaruh nyata terhadap daya tetas telur

Molecular Therapeutic Potency of Metformin by Targeting p53-Related Molecules in Mutant p53 Colon Cancer Cell Line

Colon cancer is a malignancy in gastrointestinal tract. It causes high mortality rate in global cancer population. However, chemotherapy as its first option therapy is still controversial due to its effectiveness and its adverse effects. Finding supportive and alternative drugs to cure cancer is one of focus in cancer research. A drug which also has anticancer effects is metformin. Metformin is a biguanide antidiabetic which show its potential anticancer benefit in metabolic-related cancers including colon cancer. To investigate anticancer potency of metformin in targeting p53-related molecules. Metformin treatment were divided into 4 groups by 0, 5, 10 and 20 mM concentrations and incubated in 37o C and 5 % CO2 condition for 48 hours. Immunohistochemistry were conducted to asses level of expression of Bax, p21, cyclin D1 and E2F1, respectively. Level of expression were measured by H-SCORE using percentage and intensity calculation. Comparisons of H-SCORE between groups were performed by ANOVA for parametrical data and Kruskal-Wallis for non-parametrical data. Growth inhibition were observed after metformin treatment. Metformin increases Bax expression significantly at all concentrations. p21 expression was also increased after metformin treatment but is not statistically significant. Subsequently, metformin decreases cyclin D1 expression at 10 and 20 mM concentration thus decreased E2F1 expression at 5 and 10 mM concentration. These data suggest that metformin may have potential therapeutic effects in mutant p53 colon cancer cell line by targeting p53-related molecules.Keywords: Colon cancer; p53; Biguanide; Metformin; p53-mutant cell lin

The association of food ingredients in breakfast cereal products and fumonisins production: risks identification and predictions

Breakfast processed products are remarkably at risk of fungal contamination. This research surveyed the fumonisins concentration in different breakfast products, and carried out in-vitro experiments measuring fumonisins content in different substrates inoculated with Fusarium verticillioides. The pipeline started with the identification of combinations of ingredients for 58 breakfast products. Twenty-three core ingredients, seven nutritional components and production types were analyzed using a Pearson correlation, k-means clustering and principal component analysis to show that no single factor is responsible for high fumonisins detection in processed cereals products. Consequently, decision tree regression was used as a means of determining and visualizing complex logical interactions between the same factors. We clustered the association of ingredients in low, medium, and high risk of fumonisin detection. The analysis showed that high fumonisins concentration is associated with those products that have high maize concentrations coupled especially with high sodium or rice. In a in-vitro experiment, different media were prepared by mixing the ingredients in the proportion found in the first survey and by measuring fumonisins production by Fusarium verticillioides. Results showed that: 1) fumonisins production by F. verticillioides is boosted by the synergistic effect of maize and highly ready carbohydrate content such as white flour; 2) a combination of maize >26%(w/w), rice >2.5%(w/w), NaCl >2.2%(w/w) led to high fumonisins production, while mono-ingredient products were more protective against fumonisins production. The observations in the in-vitro experiments appeared to align with the decision tree model that an increase in ingredient complexity can lead to fumonisins production by Fusarium. However, more research is urgently needed to develop the area of predictive mycology based on the association of processing, ingredients, fungal development, and mycotoxins production