Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Advanced glycation products (AGEs), as endogenous inflammatory mediator, compromise the physiological function of mesenchymal stem cells (MSCs). MSCs have a potential role in cell replacement therapy in acute myocardial infarction and ischemic cardiomyopathy. However, mechanisms of AGEs on MSCs are still not unveiled.</p> <p>Methods</p> <p>Reactive oxygen species (ROS), genes regulation, cell proliferation and migration have been detected by AGE-BSA stimulated MSCs.</p> <p>Results</p> <p>We found that <it>in vitro </it>stimulation with AGE-BSA induced generation of reactive oxygen species (ROS), and inhibited dose-dependently proliferation and migration of MSCs. Microarray and molecular biological assessment displayed an increased expression and secretion of Ccl2, Ccl3, Ccl4 and Il1b in a dose- and time-dependent manner. These chemokines/cytokines of equivalent concentration to those in conditioned medium exerted an inhibitory effect on MSC proliferation and migration after stimulation for 24 h. Transient elevation of phospho-p38 in MSCs upon AGE-BSA stimulation was blocked with p38 inhibitor.</p> <p>Conclusions</p> <p>The study indicates that AGE-BSA induces production of chemokines/cytokines in a dose- and time-dependent manner via activation of ROS-p38 mediated pathway. These chemokines/cytokines exert an inhibitory effect on MSC growth and migration, suggesting an amplified dysfunction of MSCs by AGEs.</p

Polygonum cuspidatum

Anoikis has been recognized as a potential target for anticancer therapy. Polygonum cuspidatum (Huzhang) is a frequently used Chinese herb in hepatocarcinoma. In present study, we evaluated the effects of Polygonum cuspidatum extract (PCE) in hepatocarcinoma cells in suspension. The results showed that PCE inhibited the proliferation of hepatocarcinoma cells in suspension in a dose- and time-dependent manner. PCE also inhibited anchorage-independent growth of hepatocarcinoma cells in soft agar. PCE induced anoikis in human hepatocarcinoma Bel-7402 cells accompanied by caspase-3 and caspase-9 activation and poly(ADP-ribose) polymerase cleavage, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. In addition, PCE treatment induced intracellular reactive oxygen species (ROS) production in Bel-7402 cells. NAC, an ROS scavenger, partially attenuated PCE-induced anoikis and activation of caspase-3 and caspase-9. Furthermore, PCE inhibited expression of focal adhesion kinase (FAK) in Bel-7402 cells. Overexpression of FAK partially abrogated PCE-induced anoikis. These data suggest that PCE may inhibit suspension growth and induce caspase-mediated anoikis in hepatocarcinoma cells and may relate to ROS generation and FAK downregulation. The present study provides new insight into the application of Chinese herb for hepatocarcinoma treatment

Phase Separation and Magnetic Order in K-doped Iron Selenide Superconductor

Alkali-doped iron selenide is the latest member of high Tc superconductor family, and its peculiar characters have immediately attracted extensive attention. We prepared high-quality potassium-doped iron selenide (KxFe2-ySe2) thin films by molecular beam epitaxy and unambiguously demonstrated the existence of phase separation, which is currently under debate, in this material using scanning tunneling microscopy and spectroscopy. The stoichiometric superconducting phase KFe2Se2 contains no iron vacancies, while the insulating phase has a \surd5\times\surd5 vacancy order. The iron vacancies are shown always destructive to superconductivity in KFe2Se2. Our study on the subgap bound states induced by the iron vacancies further reveals a magnetically-related bipartite order in the superconducting phase. These findings not only solve the existing controversies in the atomic and electronic structures in KxFe2-ySe2, but also provide valuable information on understanding the superconductivity and its interplay with magnetism in iron-based superconductors

Pengamanan Data Menggunakan Metoda Enkripsi Einstein

Dalam proses demokrasi maka semua orang bebas untuk berbicara mengutarakan pendapat dan pandangannya berdasarkan pribadi dan perasaannya, tentu saja dengan melihat bahwa hak demokrasinya tersebut tidak melanggar hak demokrasi orang lain. Kebebasan berkomunikasi ini juga termasuk kebebasan untuk berbicara dengan orang yang diinginkan. Untuk itu akan sangat mengganggu bila isi pembicaraan terutama yang menggunakan teknologi informasi ternyata bocor kepada orang yang tidak berhak dan secara demokrasi ini melanggar haknya, padahal dalam teknologi informasi yang berkembang secara sangat pesat ini ternyata tidak dibarengi dengan penggunaan alat untuk pengamanan data yang tepat dalam sistem informasi. Salah satu teknik pengamanan data informasi di dunia internet adalah penggunaan teknik algoritma kriptografi. Suatu algoritma kriptografi berisi fungsi-fungsi matematika yang digunakan untuk melakukan proses enkripsi dan dekripsi. Algoritma kriptografi yang digunakan merupakan jenis algoritma kriptografi simetrik yang menggunakan kunci rahasia yang sama untuk proses enkripsi dan dekripsinya. Pada makalah ini dipaparkan penggunaan algoritma kriptografi Einstein sebagai salah satu cara untuk mengamankan data. Pada algoritma Einstein, terdapat proses acak (random) yang menggunakan metoda kongruensial linear. Algoritma Einstein mempunyai kelebihan dalam melakukan proses enkripsi dan dekripsi pada hampir semua jenis file yang umum digunakan. Algoritma Einstein bisa diimplementasikan untuk semua ukuran file

Identification and characterization of circular RNAs in mammary gland tissue from sheep at peak lactation and during the nonlactating period

Circular RNAs are a class of noncoding RNA with a widespread occurrence in eukaryote tissues, and with some having been demonstrated to have clear biological function. In sheep, little is known about the role of circular RNAs in mammary gland tissue, and therefore an RNA sequencing approach was used to compare mammary gland tissue expression of circular RNAs in 9 Small Tail Han sheep at peak lactation, and subsequently when they were not lactating. These 9 sheep had their RNA pooled for analysis into 3 libraries from peak lactation and 3 from the nonlactating period. A total of 3,278 and 1,756 circular RNAs were identified in the peak lactation and nonlactating mammary gland tissues, respectively, and the expression and identity of 9 of them was confirmed using reverse transcriptase-polymerase chain reaction analysis and DNA sequencing. The type, chromosomal location and length of the circular RNAs identified were ascertained. Forty upregulated and one downregulated circular RNAs were characterized in the mammary gland tissue at peak lactation compared with the nonlactating mammary gland tissue. Gene ontology enrichment analysis revealed that the parental genes of these differentially expressed circular RNAs were related to molecular function, binding, protein binding, ATP binding, and ion binding. Five differentially expression circular RNAs were selected for further analysis to predict their target microRNAs, and some microRNAs reportedly associated with the development of the mammary gland were found in the constructed circular RNA–microRNA network. This study reveals the expression profiles and characterization of circular RNAs at 2 key stages of mammary gland activity, thereby providing an improved understanding of the roles of circular RNAs in the mammary gland of sheep