ABSTRACT
INTRODUCTION: White matter injury (WMI) is the most common brain injury in preterm infants and can result in life-long neurological deficits. The main cause of WMI is damage to the oligodendrocyte precursor cells (OPC) in the brain that results in delayed myelin sheath formation, or the destruction of existing myelin sheaths. OPC undergo highly regulated and strictly timed developmental changes that result in their transformation to mature oligodendrocytes capable of myelin production. OBJECTIVE: Studies have shown that clobetasol strongly promotes differentiation of OPC into myelin sheaths. Therefore, we hypothesized that clobetasol may be a therapeutic option for the treatment of preterm WMI. METHODS: We induced a WMI rat model and observed white matter damage under an optical microscope. Rats subjected to WMI were injected intraperitoneally with clobetasol (2 or 5 mg/kg daily) from day 1 to day 5 in the early treatment groups, or from day 6 to day 10 in the late treatment groups. After 17 days, the rats were sacrificed and the expression of myelin basic protein (MBP) was visualized using immunofluorescence. In addition, we evaluated myelin sheath formation using electron microscopy. The rats were also subjected to the suspension test, ramp test, and open field test to evaluate neurobehavioral functions. RESULTS: A rat model of WMI was successfully induced. It was found that clobetasol significantly induced MBP expression and myelin sheath formation and improved neurobehavioral function in the rats subjected to WMI. CONCLUSIONS: Our results indicate that clobetasol attenuates WMI by promoting OPC differentiation, and it may be an effective therapeutic agent for the treatment of preterm WMI.
Subject(s)
Brain Injuries , Oligodendrocyte Precursor Cells , White Matter , Animals , Animals, Newborn , Cell Differentiation , Clobetasol , Humans , Infant, Newborn , Infant, Premature , Myelin Sheath , Oligodendroglia , RatsABSTRACT
SCL/TAL1 interrupting locus (STIL) regulates the mitotic centrosome to promote the centriolar replication and cell cycling, and is associated with malignancies. However, the role and mechanism of STIL in gastric cancer (GC) remain elusive. STIL expression in GC tissue microarray was detected by immunohistochemistry (IHC). GC cells were transduced with control lentivirus or lentivirus for expression STIL-specific shRNA and the effect of STIL silencing on the malignant behaviors of GC cells was measured in vitro and in vivo. The potential mechanisms underlying the action of STIL were analyzed by transcriptome microarray and bioinformatics. STIL expression was up-regulated in GC tissues both in our cohort and the data from the cancer genome atlas, and positively associated with T stage and poor overall survival of GC patients. Knockdown of STIL significantly inhibited the proliferation and clonogenicity of human GC cells and attenuated the growth of implanted GC in vivo. Furthermore, STIL silencing induced cell cycle arrest in G2/M phase and apoptosis of GC cells. Transcriptome analysis indicated that STIL silencing modulated many gene expression, particularly for down-regulating the IGF-1/PI3K/AKT pathway. In addition, treatment with SC79, an AKT activator, significantly mitigated the effect of STIL-silencing in GC cells. In conclusion, STIL promotes gastric carcinogenesis and progression by enhancing the IGF-1/PI3K/AKT signaling, and STIL may be a novel target for intervention of GC.
Subject(s)
Disease Progression , Down-Regulation/genetics , Gene Knockdown Techniques , Insulin-Like Growth Factor I/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/pathology , Aged , Animals , Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Cell Proliferation/genetics , Clone Cells , Cluster Analysis , Female , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins/genetics , Male , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Signal Transduction , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Up-Regulation/geneticsABSTRACT
BACKGROUND: Apoptosis of human umbilical vein endothelial cells (HUVECs) plays an important role in the progression of Henoch-Schonlein purpura (HSP). In the present study, we explored the function of miR-218-5p in HUVEC apoptosis and HSP development. MATERIALS AND METHODS: HSP rat model was established and peripheral blood mononuclear cells (PBMC) were isolated. The expression of miR-218-5p and high-mobility group box-1 (HMGB1) protein in HUVECs was determined by quantitative real-time polymerase chain reaction and western blot, respectively. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The association between miR-218-5p and HMGB1 was determined by luciferase assay. The endogenous expression of related genes was modulated with recombinant plasmids and cell transfection. RESULTS: MiR-218-5p was down-regulated and HMGB1 was up-regulated in vessels of the lower limb of HSP rats and in HUVECs co-cultured in HSP PBMC supernatant. MiR-218-5p negatively regulated HMGB1 by targeting its 3'-untranslated regions. Over expression of miR-218-5p reversed the increased apoptosis and HMGB1 expression observed in HUVECs co-cultured in PBMC supernatant, whereas miR-218-5p knockdown showed the opposite outcomes. Furthermore, the miR-218-5p mimic demonstrated an inhibitory effect on the apoptosis of HUVECs co-cultured in PBMC supernatant, which was reversed by over expression of HMGB1. In HSP rats, over expression of miR-218-5p attenuated HSP and decreased the level of HMGB1. CONCLUSIONS: MiR-218-5p attenuated HSP at least partly through regulating HMGB1 expression and affecting the function of HUVECs.
Subject(s)
Apoptosis , Down-Regulation , HMGB1 Protein/biosynthesis , Human Umbilical Vein Endothelial Cells/metabolism , IgA Vasculitis/metabolism , MicroRNAs/biosynthesis , Animals , Gene Knockdown Techniques , HMGB1 Protein/genetics , Human Umbilical Vein Endothelial Cells/pathology , Humans , IgA Vasculitis/genetics , IgA Vasculitis/pathology , Male , MicroRNAs/genetics , Rats , Rats, Sprague-DawleyABSTRACT
AIMS: To report and evaluate the clinical value of circular stapler-assisted extraperitoneal colostomy. METHODS: We performed circular stapler-assisted extraperitoneal colostomy following Miles' operation in 22 patients over a 2-year period from March 2007 to March 2009. The efficiency and safety of the operation were evaluated. RESULTS: The length of surgery was 15 ± 5 min, and all the colostomies were successfully completed during the first procedure. No complications such as anastomotic infections, hemorrhage, necrosis, or invagination occurred after surgery. No scar contraction, stoma stenoses, intestinal obstructions, or parastomal hernias were found during the follow-up period of 24-72 months. All the colostomies functioned well. CONCLUSION: Circular stapler-assisted extraperitoneal colostomy can be a safe and effective procedure to improve the outcome of surgery for rectal cancer. This is one of the few studies attempting stapled colostomy, and at present the technique appears promising but warrants a longer follow-up period and additional study, in particular a prospective trial including a control group.
