Identification of Dental Stem Cells Similar to Skeletal Stem Cells.

Stem and progenitor cells play important roles in the development and maintenance of teeth and bone. Surface markers expressed in bone marrow-derived mesenchymal stem cells are also expressed in dental tissue-derived stem cells. Mouse skeletal stem cells (mSSCs, CD45-Ter119-Tie2-CD51+Thy-6C3-CD105-CD200+) and human skeletal stem cells (hSSCs, CD45-CD235a-TIE2-CD31-CD146-PDPN+CD73+CD164+) have been identified in bone and shown to play important roles in skeletal development and regeneration. However, it is unclear whether dental tissues also harbor mSSC or hSSC populations. Here, we employed rainbow tracers and found that clonal expansion occurred in mouse dental tissues similar to that in bone. We sorted the mSSC population from mouse periodontal ligament (mPDL) tissue and mouse dental pulp (mDP) tissue in the lower incisors by fluorescence-activated cell sorting (FACS). In addition, we demonstrated that mPDL-derived skeletal stem cells (mPDL-SSCs) and mDP-derived skeletal stem cells (mDP-SSCs) have similar clonogenic capacity, as well as cementogenic and odontogenic potential, but not adipogenic potential, similar to the characteristics of mSSCs. Moreover, we found that the dental tissue-derived mSSC population plays an important role in repairing clipped incisors. Importantly, we sorted the hSSC population from human periodontal ligament (hPDL) and human dental pulp (hDP) tissue in molars and identified its stem cell characteristics. Finally, hPDL-like and hDP-like structures were generated after transplanting hPDL-SSCs and hDP-SSCs beneath the renal capsules. In conclusion, we demonstrated that mouse and human PDL and DP tissues harbor dental stem cells similar to mSSCs and hSSCs, respectively, providing a precise stem cell population for the exploration of dental diseases.

Identifying hub genes and dysregulated pathways in hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to identify the hub genes and dysregulated pathways of hepatocellular carcinoma (HCC) and explore the molecular mechanism of the biological process associated with HCC. MATERIALS AND METHODS: Microarray data were got from NCBI Gene Expression Omnibus (GEO) database. The most significant top 100 up-regulated gene signatures and top 100 down-regulated gene signatures were identified by integrated analysis of the multiple microarray datasets using a novel model genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). Gene Ontology (GO) enrichment analysis and pathway analysis of those genes were performed based on Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) network was constructed using Cytoscape 2.1. In addition, we analysed the significantly dysregulated signaling pathways across the PPI network and KEGG pathway analysis. RESULTS: We screened 2920 up-regulated and 2231 down-regulated gene signatures across multiple studies by GWRS and GWGS. The top 100 up-regulated and top 100 down-regulated gene signatures were selected for further research. GO enrichment analysis showed that these genes significantly enriched in terms of mitosis (p = 5.83×10-20), nuclear division (p = 5.83×10-20) and M phase of mitotic cell cycle (p = 9.39×10-20). The most significant terms of KEGG pathway included cell cycle (p = 1.33×10-8), oocyte meiosis (p = 1.41×10-4), drug metabolism (p = 2.15×10-4) and p53 signaling pathway (p = 3.57×10-4). PPI network suggested that BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 were important significant genes which were considered as hub genes. Across the PPI and pathway, cell cycle, oocyte meiosis and p53 signaling pathway were the significantly dysregulated pathways. CONCLUSIONS: Our study displayed robust gene signatures in HCC. It showed that the dysregulations of cell cycle, oocyte meiosis, p53 signaling pathway and progesterone-mediated oocyte maturation pathway were closely associated to the development and progression of HCC. Besides, genes BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 as the hub genes might play important roles for diagnosing and therapy of HCC.

Myopic foveoschisis: a clinical review.

To review the literature on epidemiology, clinical features, diagnostic imaging, natural history, management, therapeutic approaches, and prognosis of myopic foveoschisis. A systematic Pubmed search was conducted using search terms: myopia, myopic, staphyloma, foveoschisis, and myopic foveoschisis. The evidence base for each section was organised and reviewed. Where possible an authors' interpretation or conclusion is provided for each section. The term myopic foveoschisis was first coined in 1999. It is associated with posterior staphyloma in high myopia, and is often asymptomatic initially but progresses slowly, leading to loss of central vision from foveal detachment or macular hole formation. Optical coherence tomography is used to diagnose the splitting of the neural retina into a thicker inner layer and a thinner outer layer, but compound variants of the splits have been identified. Vitrectomy with an internal limiting membrane peel and gas tamponade is the preferred approach for eyes with vision decline. There has been a surge of new information on myopic foveoschisis. Advances in optical coherence tomography will continually improve our understanding of the pathogenesis of retinal splitting, and the mechanisms that lead to macular damage and visual loss. Currently, there is a good level of consensus that surgical intervention should be considered when there is progressive visual decline from myopic foveoschisis.

Prognostic factors and survival in patients treated surgically for recurrent metastatic uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (LMS) is a rare diagnosis, which is seldom cured when it recurs with metastatic disease. We evaluated patients who present with first time recurrence treated surgically to determine prognostic factors associated with long-term survival. METHODS: Over a 16-year period, 41 patients were operated on for recurrent uterine sarcoma. Data examined included patient age, date of initial diagnosis, tumor histology, grade at the initial diagnosis, cytopathology changes in tumor activity from the initial diagnosis, residual tumor after all operations, use of adjuvant therapy, dates and sites of all recurrences, and disease status at last followup. RESULTS: 24 patients were operated for first recurrence of metastatic uterine LMS. Complete tumor resection with histologic negative margins was achieved in 16 (67%) patients. Overall survival was significantly affected by the FIGO stage at the time of the initial diagnosis, the ability to obtain complete tumor resection at the time of surgery for first time recurrent disease, single tumor recurrence, and recurrence greater than 12 months from the time of the initial diagnosis. Median disease-free survival was 14 months and overall survival was 27 months. CONCLUSION: Our findings suggest that stage 1 at the time of initial diagnosis, recurrence greater than 12 months, isolated tumor recurrence, and the ability to remove ability to perform complete tumor resection at the time of the first recurrence can afford improved survival in selected patientsat the time of the first recurrence can afford improved survival in selected patients.

Protection against ischemia-reperfusion injury in aged liver donor by the induction of exogenous human telomerase reverse transcriptase gene.

BACKGROUND: Liver ischemia-reperfusion (I/R) injury is of great importance in primary graft dysfunction after transplantation, and could be more severe in transplantation using aged donor livers. In order to alleviate the I/R injury in aged donor livers, we transferred exogenous human telomerase reverse transcriptase (hTERT) gene into aged rat's livers before liver transplantation. After transplantation, the effect of the gene for aged rats on cell apoptosis caused by I/R injury was evaluated. METHODS: The experiment was divided into 2 parts: comparative experiment between aged rats and adult rats, and exogenous induction experiment of aged rats. In the first part, Wistar rats were divided into 2 groups; group I was composed of adult rats (5 months) and group II was composed of aged rats (16-18 months). After successful transplantation, chronic oxidative stress and lipid peroxidation-related indicators (contents of vitamin C and vitamin E; activities of superoxide dismutase, catalase, and methane decarboxylic aldehyde) and alanine aminotransferase activity were examined. In the second part, additional aged rats were divided into 3 groups: group A included the donors pretreated with exogenous hTERT gene; group B included the donors pretreated with adenovirus vector; and group C was composed of the donors pretreated with physiological saline. Various indicators were detected to analyze the effect of the gene on I/R injury of the aged rats. RESULTS: The lower vitamin C, vitamin E, SOD, and CAT contents in the aged group than those in the adult group (P < .05), and the higher MDA and ALT contents in the aged group than those in the adult group (P < .05) were observed. The apoptotic index and ALT levels in the hTERT gene-pretreated group were significantly lower than those in the adenovirus vector group and the physiological saline group (P < .05). Meanwhile, mild histological injury and increased telomerase activity were also observed in the hTERT gene-pretreated group. CONCLUSION: Compared with the adult rats, I/R injury in the aged liver donor is more severe. The induction of exogenous hTERT gene offers protection against I/R injury in the aged liver.

Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use. METHODS: Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups. RESULTS: Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids. CONCLUSIONS: This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.