Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal...Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.展开更多
Hepatitis E virus(HEV)is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries.HEV infection is considered the main cause o...Hepatitis E virus(HEV)is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries.HEV infection is considered the main cause of acute hepatitis worldwide.In some cases,transfusion of blood components or organ transplantation have been reported as the source of infection.We have conducted a literature review on the risk of transmission through cell and tissue allografts.Although no case was found,measures to control this risk should be taken when donor profile(based upon geographical and behavioural data)recommended it.Issues to be considered in donor screening and tissue processing to assess and to reduce the risk of HEV transmission are approached.展开更多
Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to ass...Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.展开更多
Transforming growth factor-beta（TGF-β）/bone morphogenetic protein（BMP） plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations o...Transforming growth factor-beta（TGF-β）/bone morphogenetic protein（BMP） plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β（I/II） or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific.Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog（Hh）, Notch, Akt/m TOR, and mi RNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, mi RNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.展开更多
Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association betwee...Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.展开更多
Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. ...Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.展开更多
Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immuno...Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.展开更多
According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when c...According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.展开更多
AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fix...AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.展开更多
AIM： To determine the functional significance of aryl hydrocarbon receptor （AhR） in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer （GC） treatment. METHODS： RT-PCR, real-time PC...AIM： To determine the functional significance of aryl hydrocarbon receptor （AhR） in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer （GC） treatment. METHODS： RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry （IHC） in 290 samples： 30 chronic superficial gastritis （CSG）, 30 chronic atrophic gastritis （CAG）, 30 intestinal metapiasia （IN）, 30 atypical hyperplasia （AH）, and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin （TCDD） was used to treat AGS cells. MTr assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.RESULTS： AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION： AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.展开更多
Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have ...Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have proved that procaine,an inhibitor of DNA methyltransferases,could inhibit the proliferation of T24 and 5637 human bladder cancer cells by inducing their apoptosis.The mechanism studies reveal that procaine could induce demethylation of APAF1 gene in T24 or 5637 cells,subsequently activating caspase-3/9.It was also shown that the serum soluble fas ligand（sFasL） was activated,and the expression of matrix metallopeptidase 9（MMP-9） was down-regulated.Procaine seems to induce cell death by different pathways,and it might be used as a potential agent for bladder cancer treatment.展开更多
Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or b...Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or biological agents)in the mid-term to avoid colectomy.Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer,particularly in elderly and co-morbid patients,underlining the unmet need for safer alternative therapies.Granulocyte/monocytapheresis(GMA),a CE-marked,non-pharmacological procedure for the treatment of ulcerative colitis(among other immune-mediated diseases),remains the only therapy targeting neutrophils,the hallmark of pathology in ulcerative colitis.GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile.In spite of being a first line therapy in Japan,GMA use is still limited to a small number of centres and countries in Europe.In this article,we aim to give an overview from a European perspective of the mechanism of action,recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.展开更多
OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers ...OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were ＂glioma＂, ＂polymorphism＂, and ＂XRCC1 or X-ray repair cross-complementing group 1＂. References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION： Studies were identified according to the following inclusion criteria： case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio （OR） and 95% confidence interval （CI）. Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger＇s test using Stata 12.0 software. MAIN OUTCOME MEASURES： Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS： Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model （Gin/Gin ＋ GIn/Arg versus Arg/Arg： OR = 1.26, 95%CI= 1.03-1.54, P = 0.02）. In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive （OR = 1.46, 95%CI= 1.04-2.45, P = 0.03） and dominant models （OR = 1.40, 95%CI= 1.10-1.78, P = 0.007）, and homozygote contrast （OR = 1.69, 95%CI= 1.17-2.45, P = 0.005）, but not in Caucasian sub- jects. For association of the Arg194Trp （eight studies） and Arg280His （four studies） polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION： The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.展开更多
OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organel...OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organelles.Exposure to excessive manganese(Mn) causes neurotoxicity and can produce a Parkinson disease(PD)-like neurological disorder.Mitochondrial dysfunction and oxidative stress are implicated in the mechanism of Mn induced neurotoxicity.The present study was designed to determine whether Dendrobium nobile Lindl.alkaloids(DNLA),a Chinese medicinal herb extract,confers protective function over Mn-induced cell toxicity,and to investigate whether the modulation of PINK1/Parkin-mediated autophagy is involved in the mechanism of DNLA-mediated cell protection over Mn toxicity.METHODS AND RESULTS Rat adrenal pheochromocytoma PC12 cells were utilized as an in vitro model of Mn cell toxicity.It was found that the treatment of the PC12 cells with Mn resulted in concentration-dependent cell death,accompanied by a decrease in mitochondrial respiration capacity and an increase in ROS generation,whereas pretreatment of cells with DNLA significantly alleviated cell toxicity induced by Mn and improved mitochondrial function and oxidative status.Mn treatment enhanced apoptotic cells along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein.On the contrary,DNLA increased Bcl-2 expression,and concomitantly dramatically decreased the Bax/Bcl-2 ratio.Analysis of the expression of PINK1 and Parkin revealed that pretreatment of cells with DNLA significantly alleviated the decrease in protein levels of both PINK1 and Parkin caused by Mn.Furthermore,cells treated with Mn exhibited increased expression of LC3-Ⅱ and a decrease in accumulation of P62,which was noticeably reversed by the pretreatment of cells with DNLA.CONCLUSION DNLA inhibits Mn induced cytotoxicity,which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.展开更多
Objective： To explore the association of membrane-associated guanylate kinase inverted 1（MAGI1） with gastric cancer（GC） and the related molecular mechanisms.Methods： The reverse transcription-polymerase chain re...Objective： To explore the association of membrane-associated guanylate kinase inverted 1（MAGI1） with gastric cancer（GC） and the related molecular mechanisms.Methods： The reverse transcription-polymerase chain reaction（RT-PCR） and immunohistochemistry（IHC）were utilized to measure the MAGI1 expression level in GC tissues. Quantitative real-time PCR and Western blotting were used to ensure the MAGI1 expression in GC cell lines. Small hairpin RNA（sh RNA） was applied for knockdown of endogenous MAGI1 in GC cells. MTT assay and colony formation assay, scratch wounding migration assay and transwell chamber migration assay, as well as transwell chamber invasion assay were employed respectively to investigate the GC cell proliferation, migration and invasion in MAGI1-knockdown and control GC cells. The potential molecular mechanism mediated by MAGI1 was studied using Western blotting and RT- PCR.Results： RT-PCR and IHC verified MAGI1 was frequently expressed in matched adjacent noncancerous mucosa compared with GC tissues and the expression of MAGI1 was related to clinical pathological parameters. Functional assays indicated that MAGI1 knockdown significantly promoted GC cell migration and invasion. Further mechanism investigation demonstrated that one pathway of MAGI1 inhibiting migration and invasion was mainly by altering the expression of matrix metalloproteinases（MMPs） and epithelial-mesenchymal transition（EMT）-related molecules via inhibiting MAPK/ERK signaling pathway.Conclusions： MAGI1 was associated with GC clinical pathological parameters and acted as a tumor suppressor via inhibiting of MAPK/ERK signaling pathway in GC.展开更多
The aim of the present work is to evaluate the putative antidepressant-like effects of pomegranate fruit extract including seeds (PFE) on the performance of male mice in the forced swimming test (FST), after acute adm...The aim of the present work is to evaluate the putative antidepressant-like effects of pomegranate fruit extract including seeds (PFE) on the performance of male mice in the forced swimming test (FST), after acute administration, after short-term treatment (7 days) and, after repeated administration in a 24-h period (24, 12 and 1 h before swimming test). A single dose (20 ml/kg p.o.) of PFE, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with short-term treatment (7 days) with doses of 1 and 10 ml/kg/day of PFE. Moreover, it was noted that there were important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with PFE. Both efficacy and potency were higher when repeated administration of PFE was used, and surprisingly the dose of 10 ml/kg (24, 12 and 1 h before swimming test) was as effective as Fluoxetine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the PFE in comparison to a single dose treatment. These results indicate an antidepressant-like profile of action for PFE which deserves further research.展开更多
Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been ...Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.展开更多
基金Project supported by the 111 Project(No.B13026)the National High-Tech R&D Program(863)of China(No.2012AA02A601)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
文摘Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.
文摘Hepatitis E virus(HEV)is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries.HEV infection is considered the main cause of acute hepatitis worldwide.In some cases,transfusion of blood components or organ transplantation have been reported as the source of infection.We have conducted a literature review on the risk of transmission through cell and tissue allografts.Although no case was found,measures to control this risk should be taken when donor profile(based upon geographical and behavioural data)recommended it.Issues to be considered in donor screening and tissue processing to assess and to reduce the risk of HEV transmission are approached.
文摘Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.
文摘Transforming growth factor-beta（TGF-β）/bone morphogenetic protein（BMP） plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β（I/II） or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific.Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog（Hh）, Notch, Akt/m TOR, and mi RNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, mi RNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.
文摘Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.
基金supported by the grants of the Foundation from Beijing Municipal Committee of Science and Technology (No. D0905001040631)the Scientific Research Foundation for the Returned Overseas Chinese Scholars from Ministry of Education of China
文摘Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.
文摘Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.
文摘According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.
基金Supported by A grant from the Beijing Municipal Science and Technology Commission’s NOVA Program,No.2009BG-02Beijing Municipal Health System Special funds of High-Level Medical Personnel Construction,No.2013-3-082
文摘AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.
基金Supported by The grants from National Natural Science Foundation of China, No. 30871145, No. 30670949 and No. 30671904the grant awarded to PhD supervisor from Chinese Ministry of Education, No. 20060558010+1 种基金the grant awarded to new teacher from Chinese Ministry of Education No. 20070558288the grants from the Natural Science Foundation of Guangdong Province, No. 5300767 and No. 7001641
文摘AIM： To determine the functional significance of aryl hydrocarbon receptor （AhR） in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer （GC） treatment. METHODS： RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry （IHC） in 290 samples： 30 chronic superficial gastritis （CSG）, 30 chronic atrophic gastritis （CAG）, 30 intestinal metapiasia （IN）, 30 atypical hyperplasia （AH）, and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin （TCDD） was used to treat AGS cells. MTr assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.RESULTS： AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION： AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.
基金Supported by the National Natural Science Foundation of China(Nos.81001298,81241093)the Project of China Postdoctoral Science Foundation(No.20100481058)+2 种基金the High-tech Industrial Development Project of Jilin Province,China(No.20090633)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20100061120028)the Scientific Research Foundation of Jilin Province,China(Nos.20080739,200905169)
文摘Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have proved that procaine,an inhibitor of DNA methyltransferases,could inhibit the proliferation of T24 and 5637 human bladder cancer cells by inducing their apoptosis.The mechanism studies reveal that procaine could induce demethylation of APAF1 gene in T24 or 5637 cells,subsequently activating caspase-3/9.It was also shown that the serum soluble fas ligand（sFasL） was activated,and the expression of matrix metallopeptidase 9（MMP-9） was down-regulated.Procaine seems to induce cell death by different pathways,and it might be used as a potential agent for bladder cancer treatment.
文摘Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or biological agents)in the mid-term to avoid colectomy.Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer,particularly in elderly and co-morbid patients,underlining the unmet need for safer alternative therapies.Granulocyte/monocytapheresis(GMA),a CE-marked,non-pharmacological procedure for the treatment of ulcerative colitis(among other immune-mediated diseases),remains the only therapy targeting neutrophils,the hallmark of pathology in ulcerative colitis.GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile.In spite of being a first line therapy in Japan,GMA use is still limited to a small number of centres and countries in Europe.In this article,we aim to give an overview from a European perspective of the mechanism of action,recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.
基金The Fundamental Research Funds for Jilin University in China,No.450060445246the High-Tech Industrial Development Project of Jilin Province in China,No.20090633+1 种基金the Scientific Research Foundation of Jilin Province in China,No.20130206001YY,20120713 and 200905169the Scientific Research Foundation of Changchun in China,No.12SF29
文摘OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were ＂glioma＂, ＂polymorphism＂, and ＂XRCC1 or X-ray repair cross-complementing group 1＂. References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION： Studies were identified according to the following inclusion criteria： case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio （OR） and 95% confidence interval （CI）. Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger＇s test using Stata 12.0 software. MAIN OUTCOME MEASURES： Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS： Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model （Gin/Gin ＋ GIn/Arg versus Arg/Arg： OR = 1.26, 95%CI= 1.03-1.54, P = 0.02）. In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive （OR = 1.46, 95%CI= 1.04-2.45, P = 0.03） and dominant models （OR = 1.40, 95%CI= 1.10-1.78, P = 0.007）, and homozygote contrast （OR = 1.69, 95%CI= 1.17-2.45, P = 0.005）, but not in Caucasian sub- jects. For association of the Arg194Trp （eight studies） and Arg280His （four studies） polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION： The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.
文摘OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organelles.Exposure to excessive manganese(Mn) causes neurotoxicity and can produce a Parkinson disease(PD)-like neurological disorder.Mitochondrial dysfunction and oxidative stress are implicated in the mechanism of Mn induced neurotoxicity.The present study was designed to determine whether Dendrobium nobile Lindl.alkaloids(DNLA),a Chinese medicinal herb extract,confers protective function over Mn-induced cell toxicity,and to investigate whether the modulation of PINK1/Parkin-mediated autophagy is involved in the mechanism of DNLA-mediated cell protection over Mn toxicity.METHODS AND RESULTS Rat adrenal pheochromocytoma PC12 cells were utilized as an in vitro model of Mn cell toxicity.It was found that the treatment of the PC12 cells with Mn resulted in concentration-dependent cell death,accompanied by a decrease in mitochondrial respiration capacity and an increase in ROS generation,whereas pretreatment of cells with DNLA significantly alleviated cell toxicity induced by Mn and improved mitochondrial function and oxidative status.Mn treatment enhanced apoptotic cells along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein.On the contrary,DNLA increased Bcl-2 expression,and concomitantly dramatically decreased the Bax/Bcl-2 ratio.Analysis of the expression of PINK1 and Parkin revealed that pretreatment of cells with DNLA significantly alleviated the decrease in protein levels of both PINK1 and Parkin caused by Mn.Furthermore,cells treated with Mn exhibited increased expression of LC3-Ⅱ and a decrease in accumulation of P62,which was noticeably reversed by the pretreatment of cells with DNLA.CONCLUSION DNLA inhibits Mn induced cytotoxicity,which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.
基金supported by the Young Talents of Science and Technology Support Project of Colleges and Universities of Inner Mongolia Autonomous Region (NJYT-12-B21, 2012)the Great Project of the Affiliated Hospital of Inner Mongolia Medical University (No. NYFY ZD 2012014)+3 种基金the National Natural Science Foundation of China (No. 81260363)Beijing Municipal Administration of Hospitals’ Youth Programme (No. QML20151003)the Project supported by National Science and Technology Ministry (No. 2014BAI09B02)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201701)
文摘Objective： To explore the association of membrane-associated guanylate kinase inverted 1（MAGI1） with gastric cancer（GC） and the related molecular mechanisms.Methods： The reverse transcription-polymerase chain reaction（RT-PCR） and immunohistochemistry（IHC）were utilized to measure the MAGI1 expression level in GC tissues. Quantitative real-time PCR and Western blotting were used to ensure the MAGI1 expression in GC cell lines. Small hairpin RNA（sh RNA） was applied for knockdown of endogenous MAGI1 in GC cells. MTT assay and colony formation assay, scratch wounding migration assay and transwell chamber migration assay, as well as transwell chamber invasion assay were employed respectively to investigate the GC cell proliferation, migration and invasion in MAGI1-knockdown and control GC cells. The potential molecular mechanism mediated by MAGI1 was studied using Western blotting and RT- PCR.Results： RT-PCR and IHC verified MAGI1 was frequently expressed in matched adjacent noncancerous mucosa compared with GC tissues and the expression of MAGI1 was related to clinical pathological parameters. Functional assays indicated that MAGI1 knockdown significantly promoted GC cell migration and invasion. Further mechanism investigation demonstrated that one pathway of MAGI1 inhibiting migration and invasion was mainly by altering the expression of matrix metalloproteinases（MMPs） and epithelial-mesenchymal transition（EMT）-related molecules via inhibiting MAPK/ERK signaling pathway.Conclusions： MAGI1 was associated with GC clinical pathological parameters and acted as a tumor suppressor via inhibiting of MAPK/ERK signaling pathway in GC.
文摘The aim of the present work is to evaluate the putative antidepressant-like effects of pomegranate fruit extract including seeds (PFE) on the performance of male mice in the forced swimming test (FST), after acute administration, after short-term treatment (7 days) and, after repeated administration in a 24-h period (24, 12 and 1 h before swimming test). A single dose (20 ml/kg p.o.) of PFE, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with short-term treatment (7 days) with doses of 1 and 10 ml/kg/day of PFE. Moreover, it was noted that there were important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with PFE. Both efficacy and potency were higher when repeated administration of PFE was used, and surprisingly the dose of 10 ml/kg (24, 12 and 1 h before swimming test) was as effective as Fluoxetine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the PFE in comparison to a single dose treatment. These results indicate an antidepressant-like profile of action for PFE which deserves further research.
文摘Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.
