LOC285629 regulates cell proliferation and motility in colorectal cancer cells.

PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC. METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler. RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K. CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

In vitro characterization and mechanical properties of ß-calcium silicate/POC composite as a bone fixation device.

Calcium silicate (CS, CaSiO3 ) is a bioactive, degradable, and biocompatible ceramic and has been considered for its potential in the field of orthopedic surgery. The objective of this study is the fabrication and characterization of the ß-CS/poly(1.8-octanediol citrate) (POC) biocomposite, with the goals of controlling its weight loss and improving its biological and mechanical properties. POC is one of the most biocompatible polymers, and it is widely used in biomedical engineering applications. The degradation and bioactivity of the composites were determined by soaking the composites in phosphate-buffered saline and simulated body fluid, respectively. Human osteoblast cells were cultured on the composites to determine their cell proliferation and adhesion. The results illustrated that the flexural and compressive strengths were significantly enhanced by a modification of 40% POC. It was also concluded that the degradation bioactivity and amelioration of cell proliferation increased significantly with an increasing ß-CS content.

Genetics and genomics of Sjögren's syndrome: research provides clues to pathogenesis and novel therapies.

PURPOSE: Although the key inciting events that drive the progression from autoantibodies to clinical disease remain to be clarified, new light has been shed on the factors contributing to disease susceptibility and the role of genetic factors in determining Sjögren's syndrome (SS) disease phenotypes. The purpose of this article is to provide an update on the role of genetic markers in the susceptibility to and pathogenesis of SS. This article also discusses how genomic and proteomic technology can help in the design of specific therapeutics. KEY FINDINGS: Recent evidence suggests that inflammatory genes associated with interferon pathways, and specific regulatory genes that control the maturation and proliferation of B cells, contribute to the pathogenesis of SS. Both gene expression profiling technology and gene association studies have been used to identify these key biological pathways. Molecularly, defined subsets of pSS patients are also being revealed by these studies. Previously, identified gene loci that predispose to multiple autoimmune disorders have been confirmed supporting the paradigm of "general" autoimmune disease genes. Association of SS with many additional susceptibility loci are likely to be established through ongoing genome-wide association scans (GWAS). Clues from genetic studies suggest that targeting B cells will prove to be an effective way of reducing the systemic manifestations of pSS and are supported by early clinical trials. SUMMARY: Genome-wide technologies are likely to identify new genes and molecular pathways in the pathogenesis of SS that will be useful not only to identify patients at risk for SS, but also to identify subsets of patients at risk for variable levels of disease severity. In the future, these studies could identify novel biomarkers that will lead to significant advances in management by providing the means to tailor therapeutic strategies to individual patients.

Therapeutic doses of radiation alter proliferation and attachment of osteoblasts to implant surfaces.

Osseointegration of implants in irradiated bone is inadequate. The effect of radiation on cell-implant material interaction has not been adequately studied. The goal of this study was to investigate the effects of ionizing radiationon the proliferation, differentiation, and attachment of osteoblasts to commercially pure titanium (cpTi). Human fetal osteoblasts (hFOB) were irradiated either before or after plating in tissue culture (TC) dishes with or without cpTi disks. Radiation was single dose of 10 cGy, 25 cGy, 50 cGy, 1 Gy, 2 Gy, 4 Gy or 8 Gy. Cell proliferation was determined by counting trypsinized cells on 7 days after irradiation. Attachment of irradiated hFOB was measured indirectly by counting cells 2 and 6 h after plating. Differentiation was evaluated by alkaline phosphatase activity. Compared with nonirradiated sham controls, higher doses of radiation significantly reduced cell attachment and proliferation. Both proliferation and attachment were significantly lower on cpTi compared with TC. Attachment decreased based on the length of postirradiation period. Although differentiation was significantly enhanced by a dose of 8 Gy, proliferation was lowest. These initial studies show that effects of therapeutic doses of radiation on osteoblasts varied depending on the surface, time-elapsed, and amount of radiation.

International pediatric emergency care: establishment of a new specialty in a developing country.

BACKGROUND: Emergency medicine is being established as a unique and independent specialty throughout the world. Pediatric emergency medicine, however, is a relatively new subspecialty in the United States and a newer subspecialty in the rest of the world. In most of Europe and Asia, this specialty has yet to be developed. OBJECTIVE: To analyze the establishment of a new pediatric emergency care system in a developing country and identify areas of need and potential collaboration. SETTING: Pristina University Hospital, the main academic medical center in Kosovo, Federal Republic of Yugoslavia. METHODS: Data were collected using convenience sample surveys of all emergency visits in 2001, hospital admissions, health department statistics, and interviews with government officials and healthcare providers. RESULTS: Emergency care of children in Kosovo is provided by three parallel 24-hour clinic systems. During 2001, approximately 31,000 children sought emergency care (10,000 in the pediatric clinic, 5000 in an emergency facility, and 16,000 in the infectious disease clinic). There was no coordination or cooperation between these different facilities. No attempt was made to diagnose acute otitis media or urinary tract infection in young children. No records were kept. No physician in this study had pediatric emergency medicine and/or emergency medicine training. Prehospital providers had limited equipment and training. CONCLUSIONS: Hospital clinic systems in this environment provide high-volume and often a high level of acute care. Barriers to improved care include limited specialized training, lack of coordination between departments, and failure to establish a medical records system.

Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.

Calcineurin mediates repression of plasma membrane Ca2+-ATPase-4 (PMCA4) expression in neurons, whereas c-Myb is known to repress PMCA1 expression in vascular smooth muscle cells (VSMC). Here, we describe a novel mouse VSMC line (MOVAS) in which 45Ca efflux rates decreased 50%, fura 2-AM-based intracellular Ca2+ concentrations ([Ca2+]i) increased twofold, and real-time RT-PCR and Western blot revealed a approximately 40% decrease in PMCA4 expression levels from G0 to G1/S in the cell cycle, where PMCA4 constituted approximately 20% of total PMCA protein. Although calcineurin activity increased fivefold as MOVAS progressed from G0 to G1/S, inhibition of this increase with either BAPTA or retroviral transduction with peptide inhibitors of calcineurin (CAIN), or its downstream target nuclear factor of activated T cells (NFAT) (VIVIT), had no effect on the repression of PMCA4 mRNA expression at G1/S. By contrast, Ca2+-independent activity of the calmodulin-dependent protein kinase-II (CaMK-II) increased eightfold as MOVAS progressed from G0 to G1/S, and treatment with an inhibitor of CaMK-II (KN-93) or transduction of a c-Myb-neutralizing antibody significantly alleviated the G1/S-associated repression of PMCA4. These data show that G1/S-specific PMCA4 repression in proliferating VSMC is brought about by c-Myb and CaMK-II and that calcineurin may regulate cell cycle-associated [Ca2+]i through alternate targets.