Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.     

Variables of Microbial Response in Natural Soil Aggregates for Soil Characterization in Different Fluvial Land Shapes

The main objective of this study was to determine changes in microbial response in natural soil aggregates for soil characterization in different fluvial land shapes. This study was carried out in fluvial lands formed on accumulated sediment depositions carried by K?z?l?rmak River. The majority soils of the study area were classified as Typic Ustifluvent and Typic Haplustept in Soil Taxonomy. It was found that macroaggregates (especially >6300 μm and 2000–4750 μm diameters) of all soil samples were higher than microaggregate of soils. In addition, it was determined that the C_org content varies between 0.41–0.91% in soil samples. C_mic content was also found higher level in aggregates involved <250 and 250–425 μm diameters as compared to other aggregate size classes. Moreover, we detected that C_org:C_mic ratio was much higher in macroaggregates than in microaggregate fractions. BR levels were also greater in macroaggregates of >6,300, 4,750–6,300 and 2,000–4,750 μm than in the other macroaggregates sizes and microaggregates. Consequently, macroaggregates have relatively more C_org level than the C_org level in microaggregates, even if the absolute values of C_mic were the lower. This study thus evidenced contrasting microbial habitats and their response in different soil aggregate size formed in various developed soils.     

The expression of Akt and ERK1/2 proteins decreased in dexamethasone-induced intrauterine growth restricted rat placental development

The placenta is a complicated tissue that lies between maternal and fetal compartments. Although the architecture of the human and rodent placentas differ a little in their details, their overall structures and the molecular mechanisms of placental developments are thought to be very similar. In rats, fetal–placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. The mechanism underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. Moreover it is still not determined that how Akt and ERK1/2 proteins related proliferation and apoptosis mechanisms are influenced by dexamethasone-induced IUGR (Intrauterine Growth Restriction) placentas. The aim of this study was to investigate the expression levels and spatio-temporal immunolocalizations of Akt, p-Akt, ERK1/2 and p-ERK1/2 proteins in normal and dexamethasone treated placental development in pregnant Wistar rats. Pregnant rats were subcutaneously injected with 100 μg/kg dexamethasone 21-acetate in 0.1 ml 10% ethanol on day 10 and 12 of gestation. Afterwards injection was continued as 200 μg/kg until they were killed on day 12 (injection started on day 10), 14, 16, 18 and 20 (injections started on day 12) of pregnancy. Placental and embryonal tissues were collected for immunohistochemistry and Western blot analysis. We found that maternal dexamethasone treatment led to a decrease in ERK1/2 and Akt activation during rat placental development. The decrease in Akt and ERK1/2 activations may result with cell survival inhibition or apoptosis stimulation. Hence, dexamethasone induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 activation.     

Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1)

We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial-mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-beta family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions.     

Transglutaminase 2: a molecular Swiss army knife

Transglutaminase 2 (TG2) is the most widely distributed member of the transglutaminase family with almost all cell types in the body expressing TG2 to varying extents. In addition to being widely expressed, TG2 is an extremely versatile protein exhibiting transamidating, protein disulphide isomerase and guanine and adenine nucleotide binding and hydrolyzing activities. TG2 can also act as a protein scaffold or linker. This unique protein also undergoes extreme conformational changes and exhibits localization diversity. Being mainly a cytosolic protein; it is also found in the nucleus, associated with the cell membrane (inner and outer side) and with the mitochondria, and also in the extracellular matrix. These different activities, conformations and localization need to be carefully considered while assessing the role of TG2 in physiological and pathological processes. For example, it is becoming evident that the role of TG2 in cell death processes is dependent upon the cell type, stimuli, subcellular localization and conformational state of the protein. In this review we discuss in depth the conformational and functional diversity of TG2 in the context of its role in numerous cellular processes. In particular, we have highlighted how differential localization, conformation and activities of TG2 may distinctly mediate cell death processes.     

Pseudomonas aeruginosa septic arthritis of knee after intra-articular ozone injection

We describe a case of septic arthritis caused by Pseudomonas aeruginosa in an immunocompetent patient following intra-articular ozone injection into the knee. To the best of our knowledge, and after considering the current literature,we believe this case is unique as no other reports of septic arthritis caused by P. aeruginosa following intra-articular ozone injection has been made.     

miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1

Macroautophagy (autophagy) is the major intracellular degradation pathway for long-lived proteins and organelles. It helps the cell to survive a spectrum of stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Moreover, abnormalities of autophagy play a role in major health problems including cancer and neurodegenerative diseases. Yet, mechanisms controlling autophagic activity are not fully understood. Here, we describe hsa-miR-376b (miR-376b) as a new microRNA (miRNA) regulating autophagy. We showed that miR-376b expression attenuated starvation- and rapamycin-induced autophagy in MCF-7 and Huh-7 cells. We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. miR-376b target sequences were present in the 3' UTR of ATG4C and BECN1 mRNAs and introduction of mutations abolished their miR-376b responsiveness. Antagomir-mediated inactivation of the endogenous miR-376b led to an increase in ATG4C and BECN1 levels. Therefore, miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.