[Show abstract][Hide abstract] ABSTRACT: Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD.
[Show abstract][Hide abstract] ABSTRACT: The expression of novel oncogenic kinase (NOK), a member of the protein tyrosine kinase (PTK) family, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of NOK expression in NSCLC remains unclear.
BMC Cancer 06/2014; 14(1):402. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Macrophages and microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved in innate and adaptive immune responses. However, whether PD-1 is involved in the modulation of macrophage/microglial polarization is unknown. In this study, the mRNA levels of pd1 gradually increased after SCI, and PD-1 protein was found in macrophages/microglia in injured spinal cord sections. PD-1 knockout (KO) mice showed poor locomotor recovery after spinal cord crushing compared with wild-type mice. M1-type macrophages/microglia accumulated in greater numbers in the injured spinal cord of PD-1-KO mice. Under polarized stimulation, induced expression of PD-1 occurred in cultured macrophages and microglia. PD-1 suppressed M1 polarization by reducing the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and promoted M2 polarization by increasing STAT6 phosphorylation. In PD-1-KO mice, the M1 response was enhanced via the activation of STAT1 and nuclear factor-kappa B. Furthermore, PD-1 played various roles in phagocytosis in macrophages and microglia. Therefore, our results suggest that PD-1 signaling plays an important role in the regulation of macrophage/microglial polarization. Thus, deregulated PD-1 signaling may induce the polarization of macrophages/microglia toward the M1 phenotype. Overall, our results provide new insights into the modulatory mechanisms of macrophage/microglial polarization, thereby possibly facilitating the development of new therapies for SCI via the regulation of macrophage/microglial polarization through PD-1 signaling.
Journal of the American Society for Experimental NeuroTherapeutics 05/2014; · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Esophageal squamous cell carcinomas (ESCCs) are highly invasive and have poor prognoses. We investigated the role of PTPLAD2, a protein tyrosine phosphatase-like A domain (PTPLAD) family member, in ESCC carcinogenesis. Survival analysis was performed using patient data. ESCC tissue samples lost PTPLAD2 heterozygosity and had decreased PTPLAD2 expression. Low PTPLAD2 expression and high p-STAT3 correlated with poor prognosis. Overexpression of PTPLAD2 in ESCC cells reduced STAT3 phosphorylation, decreased FoxM1, inhibited proliferation and decreased in mouse xenograft tumor formation. Therefore, PTPLAD2 is a potential tumor suppressor and prognostic indicator that reduces STAT3 phosphorylation. PTPLAD2 is a possible clinical target for ESCC treatment.
[Show abstract][Hide abstract] ABSTRACT: Intussusception is rare in infants less than 4 months of age and the use of air enema for reduction of intussusception has been limited.
In this retrospective study, we analyzed the predictors of successful reduction of intussusception using air enema in infants less than 4 months of age.
This is a retrospective chart review of 97 intussusception patients of less than 4 months of age between January 2008 and December 2012. Demographic data, clinical presentation and outcomes of air enemas were collected and analyzed. We used univariate and multivariate logistic regression analyses for significant predictors of successful reduction of intussusception using air enemas.
Of the 97 infants less than 4 months of age (median age, 97.6 days; age range, 41 - 119 days), 63 (65%) were boys and 34 (35%) were girls. The duration of symptoms ranged from 5 to 53 hours, with a median of 16.3 hours. The clinical features included paroxysmal crying (75%), vomiting (68%), bloody stools (61%), and palpable abdominal masses (32%). The duration of symptoms, bloody stools and the shape of the intussusceptum were found to be significantly predictive of the outcome of air enema reduction of intussusception.
The rate of successful reduction of intussusception using air enemas in infants younger than 4 months is low. Such factors as the duration of symptoms, bloody stools and the shape of the intussusceptum are predictive of the outcome of air enema reduction of intussusception.
Journal of pediatric gastroenterology and nutrition 02/2014; · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether climate factors correlate with variations in the rate of pediatric intussusception cases presenting to the Children's Hospital in Suzhou, China.
The hospital records of 5,994 pediatric cases of intussusception who had presented between Aug 2006 and Dec 2011 were retrospectively analyzed. Demographic data and air enema reduction data were collected for each case.
The monthly rate of new intussusception cases fluctuated throughout the year generally rising from April to September with a peak from May to July. This annual cycling of intussusception incidence was highly significant over the 5 year observation period. Poisson regression analysis showed that the monthly number of intussusception cases was associated with an increase in mean temperature per month (P = 0.0001), sum of sunshine per month (P<0.0001), precipitation per month (P<0.0001), and was marginally associated with increased mean wind speed per month (P = 0.0709).
The incidence of intussusception in Suzhou was seasonally variable with a peak in cases presenting during hotter, sunnier, and wetter months demonstrating a positive association with certain climatic factors.
PLoS ONE 01/2014; 9(2):e90521. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a previous study, we generated two monoclonal antibodies (mAbs) in mice, aNogoA-N and aNogo-66 mAb, which were raised against recombinant N-terminal fragments of rat NogoA and Nogo-66, respectively. When compared with the commercial rabbit anti-rat NogoA polyclonal antibody (pAb), which can specifically recognise NogoA, the two mAbs were also specific for the NogoA antigen in immunofluorescence histochemical (IHC) staining and Western blot (WB) analysis. Serial truncations of NogoA covering the N-terminal region of NogoA (aa 570-691) and Nogo-66 (aa 1026-1091) were expressed in E. coli. The epitopes recognised by aNogoA-N and aNogo-66 are located in the aa 634-668 and aa 1026-1055 regions of NogoA, respectively. Both mAbs remarkably enhanced the axon growth and branching of cultured hippocampal neurons in vitro. These results suggest that the antibodies that bind to aa 634-668 and aa 1026-1055 of NogoA may have stimulatory effects on axon growth and branching. Additionally, the two mAbs that we generated are specific for NogoA and significantly block NogoA function. In conclusion, two sites in NogoA located within aa 634-668 and aa 1026-1055 are recognised by our two antibodies and are novel and potentially promising targets for repair after central nervous system (CNS) injury.
PLoS ONE 01/2014; 9(2):e88554. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinical value of MRI examination in congenital anorectal malformation (CARM).
Forty-four cases with operatively proved anorectal malformation from May 2008 to May 2012 in the authors' hospital were reviewed. Of the 44 cases, 25 were males and 19 females, their age ranged from 1 day to 2 years. MRI was performed in all patients.
Of all 44 cases, 15 cases had high imperforate anus (34%), rectum blind end were above PC line, the distance of rectum blind end and anus nest was (29.12 ± 2.35) mm; 8 cases had median imperforate anus (18%), rectum blind ends were near PC line, the distance of rectum blind end and anus nest was (18.98 ± 2.21) mm; 21 cases had low imperforate anus (48%), rectum blind ends were below PC line, the distance of rectum blind end and anus nest was (7.54 ± 1.08) mm. Twenty-five cases with fistula in 44 cases were confirmed by rectal angiography and surgery, accounting for 57%. In 13 cases with fistula, the lesion could be clearly demonstrated on MRI, in the remaining 12 cases with fistula, the lesion could not be visualized clearly or no image development occurred on MRI. Of all 44 cases, 1 case had tethered cord with filum terminale lipoma, 1 case had tethered cord, 2 cases had syringomyelia, 1 case had right kidney agenesis, 1 case had hydrocele. In 44 cases of multi-planar MRI imaging could clearly show the perianal muscles developmental situation, 36 cases had perianal muscles dysplasia, amd showed levator ani muscle, puborectalis and anal sphincter asymmetry, muscle belly slim.
MRI examination has a high clinical value in CARM diagnosis, can help accurately judge the anal atresia type, display the presence and running of most of the fistula, and diagnose perianal muscle development and other systems malformations, finally provide a reliable diagnostic basis for surgical program and prognostic assessment.
Zhonghua er ke za zhi. Chinese journal of pediatrics 01/2014; 52(1):41-45.
[Show abstract][Hide abstract] ABSTRACT: Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery.
We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery.
Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)-stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α, interleukin (IL) 1β, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κB p65, p38, and extracellular signal-regulated kinase 1/2.
These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.
Journal of critical care 10/2013; · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) is the most important viral pathogen in infants and children. It is important to analyze RSV epidemic patterns and related relevant factors in order to prevent further infections and related complications.
To explore the relationship between RSV infection rate in hospitalized children from Suzhou area and climatic factors.
42,664 nasopharyngeal specimens from hospitalized children with acute respiratory infections were screened for RSV antigens using direct immunofluorescence. 472 RSV positive samples were randomly selected and performed real-time PCR to identify RSV subtype. Monthly meteorological data in Suzhou area was collected (average temperature, relative humidity, precipitation, total sunshine, and average wind speed) from 2001 to 2011. The relation between RSV infections and climatic factors was evaluated using correlation and stepwise regression analyses.
The annual RSV infection rate in hospitalized children in Suzhou from 2001 to 2011 varied between 11.85% and 27.30%. The highest monthly infection rates occurred from November to April. The time interval from November to April was considered the infection season. Seasonal RSV infection rates from 2001 to 2010 were 40.75%, 22.72%, 39.93%, 27.37%, 42.71%, 21.28%, 38.57%, 19.86%, and 29.73%. The infection rate of any season was statistically different from the next season. There was no significant difference in RSV infection rates in the 2010-2011 and 2009-2010 epidemic seasons. Among the 472 randomly selected RSV positive samples, 412 were found to be RSV subtype A (RSV-A), while 60 subtype B (RSV-B). The monthly RSV infection rate was negatively correlated with monthly average temperature (r=-0.84), total sunshine (r=-0.47), precipitation (r=-0.31), relative humidity (r=-0.20), and average wind speed (r=-0.20), (P<0.05). Stepwise regression analysis showed monthly average temperature fit into a linear model (R(2)=0.64, P<0.01) with a regression coefficient of -1.52 (t=15.21, P<0.01).
RSV infection in Suzhou occurred most frequently between November and April. The number of infections peaked every other year. Abnormally high infection rate in non-epidemic season only caused by RSV-A. Ambient temperature played an important role in the development of RSV infection.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 10/2013; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgical intervention-related trauma contributes largely to the development of postoperative immunosuppression, with reduced resistance to secondary bacterial infection. This study compared the impact of laparotomy versus laparoscopy on macrophage-associated bactericidal ability and examined whether laparotomy renders the host more susceptible to microbial infection.
BALB/c mice were randomized into control, laparotomy, and laparoscopy groups. Laparotomy, but not laparoscopy, significantly downregulated CR3 expression on macrophages, diminished macrophage-induced uptake and phagocytosis of E. coli and S. aureus, and impaired macrophage-mediated intracellular bacterial killing. Consistent with this, mice that underwent laparotomy displayed substantially higher bacterial counts in the blood and visceral organs as well as a significantly enhanced mortality rate following bacterial infection, whereas mice subjected to laparoscopy did not show any defects in their bacterial clearance.
Laparotomy has an adverse effect on host innate immunity against microbial infection by impairing macrophage-mediated phagocytosis and killing of the invaded bacteria. By contrast, laparoscopy appears to preserve macrophage-associated bactericidal ability, thus alleviating the development of postoperative immunosuppression.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Our past researches suggested that L. barbarum exhibits direct neuroprotective and immune regulatory effects on the central nervous system, which are highly related to the events involved in the spinal cord injury, but not yet been investigated. Immune responses play an important role in the development of the pathology after secondary injury, particularly the M1 and M2 types of macrophage, on which special emphasis was laid in this study. METHODS: In our previous studies L. barbarum was administrated orally from 7 days before the injury to ensure a stabilized concentration in the blood. For clinical application, L. barbarum can only be administered after the injury. Therefore, both pre-injury and post-injury administration protocols were compared. In vivo and in vitro studies were conducted and analyzed immunohistochemically, including Western blotting. RESULTS: The lesion size in the pre-treated group was much larger than that in the post-treated group. To explain this difference, we first studied the effect of L. barbarum on astrocytes, which forms the glial scar encircling the lesion. L. barbarum did not significantly affect the astrocytes. Then we studied the effect of L. barbarum on microglia/macrophages, particularly the M1 and M2 polarization. After spinal cord injury, the deleterious M1 cells dominant the early period, whereas the beneficial M2 cells dominate later. We found that in the pre-treated group L. barbarum significantly enhanced the expression of M1 cells and suppressed that of M2 cells, while in the post-treated group LBP markedly promoted the activity of M2 cells. This explained the difference between the pre- and post-treated groups. CONCLUSIONS: Lycium barbarum has been wildly accepted to have beneficial effects in various central nervous system diseases. Our finding of deleterious effect of LBP administered at early period of spinal cord injury, so that its application should be avoided, and the substantial beneficial effect of LBP when administered at later stage has an important impact for clinical application.
BMC Complementary and Alternative Medicine 03/2013; 13(1):67. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neonates and infants, due to the immaturity in their adaptive immunity, are thought to depend largely on the innate immune system for protection against bacterial infection. However, the innate immunity-mediated antimicrobial response in neonates and infants is incompletely characterized. Here, we report that infant mice were more susceptible to microbial sepsis than adult mice, with significantly reduced bacterial clearance from the circulation and visceral organs. Infant PMNs exhibited less constitutive expression of the chemokine receptor CXCR2, and bacterial infection caused further reduction of PMN CXCR2 in infant mice compared with adult mice. This correlates with diminished in vitro chemotaxis of infant PMNs toward the chemoattractant CXCL2 and impaired in vivo recruitment of infant PMNs into the infectious site. Furthermore, consistent with the reduced antimicrobial response in vivo, infant macrophages displayed an impaired bactericidal activity with a defect in phagosome maturation after ingestion of either gram-positive or gram-negative bacteria. Thus, infant mice exhibit an increased vulnerability to microbial infection with delayed bacterial clearance, which is associated with the inefficiency in their innate phagocyte-associated antimicrobial functions characterized by defects in PMN recruitment and macrophage phagosome maturation during microbial sepsis.
European Journal of Immunology 02/2013; · 4.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIM: Liver Cirrhosis is the final stage of chronic liver damage from various etiologies. It is controversial on the reversibility of cirrhosis. The aim of this study was to determine whether cirrhosis was reversible after treatment by hepatocyte nuclear factor 4α (HNF4α), a key transcriptional regulator of hepatocyte differentiation and function. METHODS: Early and advanced stages of liver cirrhosis were induced by thioacetamide administration. The adenovirus carrying HNF4α gene was injected into cirrhotic rats via tail vein. The effect of HNF4α on cirrhosis was evaluated by histological and immunohistochemical examination. RESULTS: HNF4α could remarkably resolve early stage cirrhosis to a nearly normal extent and partially ameliorate advanced cirrhosis in vivo. Enforced expression of HNF4α remarkably downregulated profibrogenic factors including α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), fibroblast-specific protein-1 (FSP-1), collagen I and III. In vivo and in vitro study revealed that HNF4α administration could inhibit extracellular signal-regulated kinase (ERK) signaling pathway through downregulation of phosphor-ERK and phosphor-JunD. In addition, HNF4α could readjust the balance between extracellular matrix (ECM) deposition and degradation through upregulation of matrix metalloproteinases and downregulation of its inhibitors. Moreover, HNF4α treatment inhibited angiogenesis as determined by CD31 and CD34 immunostaining. CONCLUSIONS: Our findings broaden the knowledge on the reversibility of different stages of cirrhosis and HNF4α could present as a promising alternative for liver cirrhosis treatment.
Journal of Digestive Diseases 02/2013; · 1.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300. Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL.
International Journal of Molecular Sciences 01/2013; 14(2):3376-94. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. YM155, a novel molecular targeted agent, suppresses survivin, which is overexpressed in many tumor types. The aim of this study was to determine the antitumor activity of YM155 in SK-NEP-1 cells. METHODS: SK-NEP-1 cell growth in vitro and in vivo was assessed by MTT and nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometric analysis was used to detect apoptosis in cell culture. Then gene expression profile of tumor cells treated with YM155 was analyzed with real-time PCR arrays. We then analyzed the expression data with MEV (Multi Experiment View) cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis tool. RESULTS: YM155 treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner. Annexin V assay, cell cycle, and activation of caspase-3 demonstrates that YM155 induced apoptosis in SK-NEP-1 cells. YM155 significantly inhibited growth of SK-NEP-1 xenografts (YM155 5 mg/kg: 1.45 +/- 0.77 cm3; YM155 10 mg/kg: 0.95 +/- 0.55 cm3) compared to DMSO group (DMSO: 3.70 +/- 2.4 cm3) or PBS group cells (PBS: 3.78 +/- 2.20 cm3, ANOVA P < 0.01). YM155 treatment decreased weight of tumors (YM155 5 mg/kg: 1.05 +/- 0.24 g; YM155 10 mg/kg: 0.72 +/- 0.17 g) compared to DMSO group (DMSO: 2.06 +/- 0.38 g) or PBS group cells (PBS: 2.36 +/- 0.43 g, ANOVA P < 0.01). Real-time PCR array analysis showed between Test group and control group there are 32 genes significantly up-regulated and 54 genes were significantly down-regulated after YM155 treatment. Ingenuity pathway analysis (IPA) showed cell death was the highest rated network with 65 focus molecules and the significance score of 44. The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to cell death, cellular function maintenance, cell morphology, carbohydrate metabolism and cellular growth and proliferation. Death receptor signaling (3.87E-19), TNFR1 signaling, induction of apoptosis by HIV1, apoptosis signaling and molecular mechanisms of cancer came out to be the top four most significant pathways. IPA analysis also showed top molecules up-regulated were BBC3, BIRC3, BIRC8, BNIP1, CASP7, CASP9, CD5, CDKN1A, CEBPG and COL4A3, top molecules down-regulated were ZNF443, UTP11L, TP73, TNFSF10, TNFRSF1B, TNFRSF25, TIAF1, STK17A, SST and SPP1, upstream regulator were NR3C1, TP53, dexamethasone , TNF and Akt. CONCLUSIONS: The present study demonstrates that YM155 treatment resulted in apoptosis and inhibition of cell proliferation of SK-NEP-1cells. YM155 had significant role and little side effect in the treatment of SK-NEP-1 xenograft tumors. Real-time PCR array analysis firstly showed expression profile of genes dyes-regulated after YM155 treatment. IPA analysis also represents new molecule mechanism of YM155 treatment, such as NR3C1 and dexamethasone may be new target of YM155. And our results may provide new clues of molecular mechanism of apoptosis induced by YM155.
BMC Cancer 12/2012; 12(1):619. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To examine the content of phosphorylated myosin regulatory light chain (P-MLC20) and myosin light-chain kinase (MLCK) in the common bile duct of pediatric patients with pancreaticobiliary maljunction (PBM) accompanied by bile duct dilatation (BDD), and investigate their potential role in PBM accompanied by BDD. METHODS: Twenty-one specimens of the common bile duct from pediatric patients with PBM accompanied by BDD were collected. P-MLC20 was examined with immunohistochemistry. The expression of P-MLC20 and MLCK was also examined with Western blot. Twenty-one specimens of the common bile duct from pediatric patients without PBM and BDD were used as controls. RESULTS: The mean optical density (MOD), mean labeling intensity (MLI) and minimum qualifying scores (MQS) of P-MLC20 were 115.6856 ± 58.1634, 21.7125 % ± 9.6555 and 21.3531 ± 6.5255, respectively. In the control group, MOD, MLI and MQS were 96.5581 ± 9.7859, 11.1813 % ± 3.6208 and 10.7819 ± 3.5323, respectively. There was no significant difference in MOD between the two groups (P > 0.05), whereas there was a significant difference in MLI and MQS between the two groups (P < 0.05). The expression of P-MLC20 and MLCK, as determined with Western blot, was also significantly higher in the PBM group than in the control group (P < 0.05). CONCLUSION: P-MLC20 is associated with increased contractile force of the smooth muscle of the common bile duct in pediatric patients with PBM accompanied by BDD. The enhanced expression of P-MLC20 in the common bile duct probably contributes to increased bile duct pressure in PBM via the MLCK pathway.
Pediatric Surgery International 12/2012; · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inhibitory co-receptor programmed death 1 (PD-1, encoded by pdcd1) and its two ligands PD-L1 and PD-L2 comprise an important immune inhibitory signaling pathway for defense against microbes and for self-tolerance. Unlike other members of the B7-CD28 family, expression of PD-L1 and PD-L2 is not limited to the immune system. In this study, we determined that a polyclonal antibody (pAb) (R&D Systems) against extracellular domains of mouse PD-L2 (mPD-L2) could recognize antigen(s) in diverse mouse tissues, including the anterior and intermediate pituitary gland, olfactory bulbs and olfactory epithelium, tongue epithelium, keratinized epithelial cells and skin and whisker hair follicles. These findings differed from previous reports of mPD-L2 localization. Reverse transcription PCR and Western blot analyses, however, were unable to detect any mPD-L2 transcripts or proteins of the 25-kD predicted molecular weight in RNA and protein extracts, respectively, from the above tissues, suggesting that the anti-mPD-L2 pAb cross-reacts with certain novel antigen(s). Developmental studies revealed that the earliest expression of mPD-L2-like antigen was in the olfactory epithelium at embryonic day 12.5 (E12.5). At E14.5, mPD-L2-like antigen was present in the skin, tongue and follicles of the skin and whiskers. The distribution patterns of mPD-L2-like antigen remained similar from E18.5 to adulthood. The results of bioinformatic analysis and other experiments suggested neural cell adhesion molecule and hemicentin-1 as candidate proteins with cross-reactivity to the anti-mPD-L2 pAb. These results demonstrate that care is required in interpreting staining patterns generated when anti-PD-L2 pAb is used to locate PD-L2-expressing cells in the central nervous system and epithelial tissues, such as the olfactory epithelium. In addition, this anti-PD-L2 pAb may be used as an alternative antibody for labeling the olfactory epithelium during embryonic development in mice.
Science China. Life sciences 10/2012; · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Magnolol, a tradition Chinese herb, displays an array of activities including antifungal, antibacterial, and antioxidant effects. To investigate the protective effect of magnolol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intratracheal instillation of magnolol (5 μg/kg) 30 min before LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. Expression of cyclooxygenase (COX)-2 in lung tissues was determined by Western blot analysis. Magnolol pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by magnolol pretreatment. The expression of COX-2 was significantly suppressed by magnolol pretreatment. Magnolol potently protected against LPS-induced ALI and the protective effects of magnolol may attribute partly to the suppression of COX-2 expression.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The Real-time PCR Array System is the ideal tool for analyzing the expression of a focused panel of genes. In this study, we will analyze the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays. METHODS: Real-time PCR array was designed and tested firstly. Then gene expression profile of 11 pediatric AML and 10 normal controls was analyzed with real-time PCR arrays. We analyzed the expression data with MEV (Multi Experiment View) cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool. RESULTS: We designed and tested 88 real-time PCR primer pairs for a quantitative gene expression analysis of key genes involved in pediatric AML. The gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. To investigate possible biological interactions of differently regulated genes, datasets representing genes with altered expression profile were imported into the Ingenuity Pathway Analysis Tool. The results revealed 12 significant networks. Of these networks, Cellular Development, Cellular Growth and Proliferation, Tumor Morphology was the highest rated network with 36 focus molecules and the significance score of 41. The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to hematological disease, cell death, cell growth and hematological system development. In the top canonical pathways, p53 and Huntington's disease signaling came out to be the top two most significant pathways with a p value of 1.5E-8 and2.95E-7, respectively. CONCLUSIONS: The present study demonstrates the gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. We found some genes dyes-regulated in pediatric AML for the first time as FASLG, HDAC4, HDAC7 and some HOX family genes. IPA analysis showed the top important pathways for pediatric AML are p53 and Huntington's disease signaling. This work may provide new clues of molecular mechanism in pediatric AML.
Cancer Cell International 09/2012; 12(1):40. · 2.09 Impact Factor