Antitumor mechanism of Se-containing polysaccharide, a novel organic selenium compound

Recent studies on the inhibition of tumor growth by Se-containing polysaccharide were reviewed. Meanwhile, the possible molecular mechanisms of the inhibition of tumor cell growth through antioxidation, induction of tumor cell apoptosis, blockade of cell cycle, and enhancement of immunity by Se-containing polysaccharide were proposed. In the end, the potential application of Se-containing polysaccharide in the prevention and treatment of tumor was elucidated.     

Dexamethasone interferes with osteoblasts formation during osteogenesis through altering IGF-1-mediated angiogenesis

Dexamethasone (Dex), a synthetic glucocorticoid (GC) with long-lasting treatment effects, has been proved to exert a modulatory effect on osteoblast proliferation and differentiation during embryonic osteogenesis. However, it is still controversial if Dex exposure influences endochondral ossification and the underlying mechanism. In this study, chick embryos in vivo and preosteoblast cell cultures in vitro were utilized to investigate the effects of Dex on osteoblast formation and differentiation during the skeletal development. We first demonstrated that Dex exposure could shorten the long bones of 17-day chick embryos in vivo, and also downregulated the expressions of osteogenesis-related genes. Next, we established that Dex exposure inhibited the proliferation and viability of preosteoblasts-MC3TC-E1 cells, and the addition of insulin-like growth factor 1 (IGF-1) could dramatically rescue these negative effects. On the basis of remarkable changes in the rescue experiments, we next verified the important role of angiogenesis in osteogenesis by culturing isolated embryonic phalanges in Dulbecco's modified Eagle's medium culture or on the chick chorioallantoic membrane (CAM). Then, we transplanted MC3T3-E1 cell masses onto the CAM. The data showed that Dex exposure reduced the vessel density within the developed cell mass, concomitantly with the downregulation of IGF-1 pathway. We verified that the inhibition of blood vessel formation caused by Dex could be rescued by IGF-1 treatment using the CAM angiogenesis model. Eventually, we demonstrated that the shortened length of the phalanges in the presence of Dex could be reversed by IGF-1 addition. In summary, these findings suggested that the inhibition of Igf-1 signal caused by Dex exposure exerts a detrimental impact on the formation of osteoblasts and angiogenesis, which consequently shortens long bones during osteogenesis.     

The sugar-specific adhesion/deadhesion apparatus of the marine bacterium Vibrio furnissii is a sensorium that continuously monitors nutrient levels in the environment

Our earlier studies on cell adhesion to immobilized carbohydrates are extended here to a marine bacterium, Vibrio furnissii. Apparently one lectin mediates the binding of these cells to glycosides of N-acetylglucosamine, mannose, and glucose covalently linked to Agarose beads. Kinetic studies show that protein synthesis is required for initiating and for maintaining adhesion to the glycosides. Furthermore, a pro- mutant binds to GlcNAc-beads at Pro concentrations insufficient to support cell growth. Expression of the functional lectin therefore predominates under conditions of limiting protein synthesis. Thus, cells adhere to the sugars in an environment compatible with protein synthesis, and deadhere when depleted of any required nutrient, presumably to migrate to a more favorable locale. The adhesion-deadhesion apparatus thereby permits constant monitoring of the surrounding environment, comprising a "nutrient sensorium".     

Errors from using 3H-labeled ribonucleoside triphosphates to monitor nuclear RNA synthesis in vitro

The [3H]XTPs are used widely to monitor RNA synthesis in vitro. Recently, we discovered that they reflected only 40-45% of the true rate of nuclear RNA synthesis. Thus, when [8-14C]GTP was used, 1466 pmol [8-14C]GMP was incorporated per mg DNA/10 min. On the other hand, when [8-3H]GTP was used, only 564 pmol [8-3H]GMP was incorporated per mg DNA/10 min. There are three obvious factors that could have contributed to this greater than 2-fold difference in the apparent incorporation rate: commercial [8-3H]GTP sample was contaminated with substances causing the assay medium to be less efficient in RNA synthesis; 3H exchange occurred during acid washing of the [3H]RNA; and there was a greater quenching effect on [3H]RNA. Experiments were designed to test each of these alternatives. We are able to conclude that none of the above three are contributing factors. Our data also show that the 3H label was removed after it was incorporated into RNA. Similar differences were observed when 3H and 14C labeled pairs of ATP, UTP and CTP were compared. Furthermore, when nuclei were fractionated into nucleolar and nucleoplasmic fractions and carried out RNA synthesis, the loss of 3H label was observed mainly from the nucleoplasmic fraction.     

布氏田鼠冷暴露中褐色脂肪组织的增补及解偶联蛋白基因表达

布氏田鼠 (Microtusbrandti)随机分组暴露在冷环境 [12L∶12D ,(4± 2 )℃ ]中 12h ,1d ,3d ,7d ,14d ,2 1d和 2 8d ;对照组生活在温暖环境下 [12L∶12D ,(2 5± 2 )℃ ]。与对照组相比 ,布氏田鼠的褐色脂肪组织 (BAT)重量在冷暴露 12h～ 3d时降低 ,7～ 2 1d时则增加。 7～ 2 8d冷暴露组动物的BAT总蛋白和总DNA含量均比对照组明显提高。冷环境中的布氏田鼠解偶联蛋白 (UCP)的mRNA随时间的延长而表达上调 ,在冷暴露 2 1d时达到高峰。结果表明 ,冷暴露能够诱导布氏田鼠BAT细胞增补和UCP基因表达 ,从而使适应性产热增加。     

Targeting cullin-RING ligases for cancer treatment: rationales,advances and therapeutic implications

New therapeutic intervention strategies for the treatment of human malignancies are always desired. Approval of bortezomib as a front-line treatment for multiple myeloma highlighted the significance of ubiquitin–proteasome system (UPS) as a promising therapeutic target. However, due to the broad impact of proteasome inhibition, deleterious side effects have been reported with bortezomib treatment. Cullin RING ligases (CRLs)-mediated ubiquitin conjugation process is responsible for the ubiquitin conjugation of 20 % cellular proteins that are designated for degradation through the UPS, most of them are critical proteins involved in cell cycle progression, signaling transduction and apoptosis. Studies have depicted the upstream NEDDylation pathway that controls the CRL activity by regulating the conjugation of an ubiquitin-like-protein NEDD8 to the cullin protein in the complex. A specific pharmaceutical inhibitor of NEDD8 activating enzyme (NAE; E1) MLN4924 was recently developed and has been promoted to Phase I clinical trials for the treatment of several human malignancies. This article summarizes the most recent understanding about the process of NEDD8 conjugation, its relevance for cancer therapy and molecular mechanisms responsible for the potent anti-tumor activity of MLN4924.     

Novel Biomarkers for Non-functioning Invasive Pituitary Adenomas were Identified by Using Analysis of microRNAs Expression Profile

The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future.     

New bivalves from the Jurassic of Iran

Three new subgenera, Gervillaria (Platygervillaria), Isognomon (Iranognomon), and Mytilaster (Persiaster), and seven new species, Gervillaria (Platygervillaria) alifera, Isognomon (Iranognomon) arkelli, Inoperna (Inoperna) striata, Mytilaster (Persiaster) ancestralis, Astarte persipulla, Orthotrigonia fazli, and Gissaromya abramovi, from the Jurassic of Iran are described.     

Transport functions and expression analysis of vacuolar membrane aquaporins in response to various stresses in rice

The vacuole, a multifunctional organelle of most plant cells, has very important roles in space filling, osmotic adjustment, storage and digestion. Previous researches suggested that aquaporins in the tonoplast were involved in vacuolar functions. The rice genome contains 33 aquaporin genes, 10 of which encode tonoplast intrinsic proteins (TIPs). However, the function of each individual TIP isoform and the integrated function of TIPs under various physiological conditions remain elusive. Here, five rice TIP members were characterized with water and/or glycerol transport activities using the Xenopus oocyte expression system. OsTIP1;2, OsTIP2;2, OsTIP4;1 and OsTIP5;1 possessed water transport activity. OsTIP1;2, OsTIP3;2 and OsTIP4;1 were demonstrated with glycerol transport activity. Rice TIP expression patterns under various abiotic stress conditions including dehydration, high salinity, abscisic acid (ABA) and during seed germination were investigated by real-time PCR. OsTIP1s (OsTIP1;1 and OsTIP1;2) were highly expressed during seed germination, whereas OsTIP3s (OsTIP3;1 and OsTIP3;2) were specifically expressed in mature seeds with a decrease in expression levels upon germination. The results of this research provided a functional and expression profiles of rice TIPs.