Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model.

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Differentiation of follicular carcinomas from adenomas using histogram obtained from diffusion-weighted MRI.

AIM: To evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps from diffusion-weighted imaging (DWI) in the differentiation of follicular thyroid carcinoma (FTC) from follicular adenoma (FA) in nodules indeterminate on ultrasound-guided core needle biopsy (USCNB). MATERIALS AND METHODS: This study was performed with institutional review board approval. Seventeen patients who were planned to undergo diagnostic lobectomy for an indeterminate thyroid nodule (atypical of unknown significance/follicular lesion of undetermined significance [AUS/FLUS] or suspicious for follicular neoplasm/follicular neoplasm [SFN]) on USCNB were enrolled prospectively. All patients underwent DWI on the day before surgery. Histogram parameters were derived from ADC values obtained from the whole extent of the tumours. The parameters were compared with the final diagnosis based on histopathological examination after surgery. The accuracy of the parameters in differentiating FTC from FA was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve patients were confirmed as having FA and five patients as having FTC. Histogram parameters including the 10th (ADC10), 25th (ADC25), and 50th (ADC50) percentiles of the ADC values were significantly lower in FA than in FTC (p < 0.05, all). ROC curve analysis revealed that ADC25 resulted in the highest AUC (0.867; confidence interval, 0.616-0.980), with a cut-off value of 0.352×10-3 mm2/s. CONCLUSION: Histogram parameters from ADC maps could differentiate FTC from FA effectively in indeterminate nodules on USCNB, with ADC25 being the most promising parameter.

Oral toxicity to high level sodium fluoride causes impairment of autophagy.

Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Human cementoblasts (HCEM-2) in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Quantitative RT-PCR and Western blotting were performed to characterize the expression levels of markers for autophagy, apoptosis, and oxidative stress. Senescence-resistant (SAMR1) mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels. HCEM-2 cells exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin-1 and LC3-II, elicited apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin-1 expression was abrogated by 5 mM NaF. Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.

A Novel Collateral Imaging Method Derived from Time-Resolved Dynamic Contrast-Enhanced MR Angiography in Acute Ischemic Stroke: A Pilot Study.

BACKGROUND AND PURPOSE: Assessment of the collateral status has been emphasized for appropriate treatment decisions in patients with acute ischemic stroke. The purpose of this study was to introduce a multiphase MRA collateral imaging method (collateral map) derived from time-resolved dynamic contrast-enhanced MRA and to verify the value of the multiphase MRA collateral map in acute ischemic stroke by comparing it with the multiphase collateral imaging method (MRP collateral map) derived from dynamic susceptibility contrast-enhanced MR perfusion. MATERIALS AND METHODS: From a prospectively maintained registry of acute ischemic stroke, MR imaging data of patients with acute ischemic stroke caused by steno-occlusive lesions of the unilateral ICA and/or the M1 segment of the MCA were analyzed. We generated collateral maps using dynamic signals from dynamic contrast-enhanced MRA and DSC-MRP using a Matlab-based in-house program and graded the collateral scores of the multiphase MRA collateral map and the MRP collateral map independently. Interobserver reliabilities and intermethod agreement between both collateral maps for collateral grading were tested. RESULTS: Seventy-one paired multiphase MRA and MRP collateral maps from 67 patients were analyzed. The interobserver reliabilities for collateral grading using multiphase MRA or MRP collateral maps were excellent (weighted κ = 0.964 and 0.956, respectively). The agreement between both collateral maps was also excellent (weighted κ = 0.884; 95% confidence interval, 0.819-0.949). CONCLUSIONS: We demonstrated that the dynamic signals of dynamic contrast-enhanced MRA could be used to generate multiphase collateral images and showed the possibility of the multiphase MRA collateral map as a useful collateral imaging method in acute ischemic stroke.

Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization.

AIM: To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP-1). METHODOLOGY: THP-1 cells were treated with resin monomers at noncytotoxic concentrations for 48 h and were analysed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co-treatment) or after treatment with monomers (pre-treatment). CD86 and CD206 mRNA in co-treated cells was evaluated using quantitative real-time polymerase chain reaction. The release of TNF-α and TGF-ß by pre-treated and co-treated cells was assessed using enzyme-linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright-field microscopy. One-way analysis of variance was used for statistical analysis. RESULTS: TEGDMA (1 mmol L-1 ) and HEMA (2 mmol L-1 ) did not induce CD86 and CD206 expressions in THP-1 cells but rather inhibited their expressions in the co-treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre-treatment with resin monomers. The release of TNF-α and TGF-ß by M1- and M2-stimulated cells, respectively, was suppressed by co-treatment (P < 0.05). Microscopic studies revealed that co-treatment with resin monomers suppressed polarization-associated morphological changes such as cell volume increase. CONCLUSIONS: TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture.

Antimicrobial activities of an oxygenated cyclohexanone derivative isolated from Amphirosellinia nigrospora JS-1675 against various plant pathogenic bacteria and fungi.

AIMS: To evaluate the antimicrobial activities of an active compound isolated from the culture broth of Amphirosellinia nigrospora JS-1675 against various plant pathogenic bacteria and fungi. METHODS AND RESULTS: While screening for bioactive secondary metabolites from endophytic fungi, we found that A. nigrospora JS-1675 showed strong in vitro antibacterial activity against Ralstonia solanacearum. One compound (1) was isolated and identified as (4S, 5S, 6S)-5,6-epoxy-4-hydroxy-3-methoxy-5-methyl-cyclohex-2-en-1-one. Growth of most of the tested phytopathogenic bacteria was inhibited by compound 1 and the ethyl acetate (EtOAc) layer except Pseudomonas syringae pv. lachrymans. Compound 1 also inhibited the mycelial growth of several plant pathogenic fungi. Both compound 1 and the EtOAc layer reduced bacterial leaf spot disease in detached peach leaves. They also suppressed the development of bacterial wilt on tomato seedlings quite effectively. CONCLUSIONS: Amphirosellinia nigrospora JS-1675 showed antimicrobial activity against plant pathogenic bacteria and fungi by producing compound 1. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the occurrence of compound 1 in A. nigrospora JS-1675 and its efficacy against plant pathogenic bacteria and fungi. Their strong disease control efficacy against tomato bacterial wilt suggests that this fungus can be used as a microbial bactericide.

Transcription factor DEC1 is required for maximal experimentally induced periodontal inflammation.

BACKGROUND AND OBJECTIVES: Disruption of transcriptional regulation is a confounding factor associated with a wide range of human inflammatory diseases. To investigate mechanistic links between transcription factor DEC1 and pathways underlying inflammation, wild-type and DEC1 knockout (KO) C57BL/6 mice were treated with Porphyromonas gingivalis (or carboxymethyl cellulose as a control) to induce periodontal inflammation. It provoked an inflammatory response within the oral environment, which showed robust variation in alveolar bone resorption and expression of inflammatory cytokines. MATERIAL AND METHODS: Male DEC1KO mice and their wild-type littermates were used for the experimental periodontitis model. Measurement of alveolar bone resorption, micro-computed tomography, isolation of gingival mononuclear cells (GMCs), flow cytometry and immunohistochemical analysis were used in this study. Human gingival fibroblast cells (HGF-1) were used for DEC1 over-expression and short interference RNA (siRNA) studies and quantitative real-time polymerase chain reaction and western blot analysis were performed. RESULTS: Micro-computed tomography analysis demonstrated that P. gingivalis caused a decrease in bone area of wild-type mice compared with DEC1KO mice. Expression of inflammatory and immune markers in GMCs was significantly decreased in DEC1KO mice after treatment with P. gingivalis. Conversely, interleukin (IL)-4 and IL-10 mRNAs were significantly increased in GMCs isolated from DEC1KO mice. The results show that treatment of DEC1KO mice with P. gingivalis decreased the numbers of CD11b+ F4/80+ and CD4+ RANKL+ T cells. Moreover, expression of CD4, F4/80, RANKL and cathepsin K in inflammatory cell infiltrates was significantly reduced in DEC1KO mice treated with P. gingivalis compared with controls. Furthermore, over-expression of DEC1 in HGF-1 cells increased the expression of IL-1ß and tumor necrosis factor-α mRNAs and their expression levels reached a maximum in response to treatment with lipopolysaccharide. Inhibition of DEC1 by short interference RNA interference suppressed the P. gingivalis-derived lipopolysaccharide-induced expression of IL-1ß, tumor necrosis factor-α and toll-like receptor4. CONCLUSION: These results suggest that transcription factor DEC1 can modulate P. gingivalis-induced periodontitis in the oral mucosa.

Effects of cell death-inducing DFF45-like effector B on meat quality traits in Berkshire pigs.

Cell death-inducing DFF45-like effector (CIDE) B is a member of the CIDE family of apoptosis-inducing factors. In the present study, we detected a single nucleotide polymorphism (SNP), c.414G>A, which corresponds to the synonymous SNP 414Arg, in CIDE-B in the Berkshire pigs. We also analyzed the relationships between the CIDE-B SNP and various meat quality traits. The SNP was significantly associated with post-mortem pH24h, water-holding capacity (WHC), fat content, protein content, drip loss, post-mortem temperature at 12 h (T12) and 24 h (T24) in a co-dominant model (P < 0.05). A significant association was detected between the SNP and post-mortem pH24h, fat content, protein content, drip loss, shear force, and T24 in gilts; and color parameter b*, WHC, and T24 in barrows (P < 0.05). The SNP was significantly correlated with the fat content, and CIDE-B mRNA expression was significantly upregulated during the early stage of adipogenesis, suggesting that CIDE-B may contribute towards initiation of adipogenesis (P < 0.05). Furthermore, CIDE-B mRNA was strongly expressed in the liver, kidney, large intestine, and small intestine, and weakly expressed in the stomach, lung, spleen, and white adipose tissue. These results indicate that the CIDE-B SNP is closely associated with meat quality traits and may be a useful DNA marker for improving pork quality.

Transoesophageal echocardiographic evaluation of central venous catheter positioning using Peres' formula or a radiological landmark-based approach: a prospective randomized single-centre study.

BACKGROUND: The lower superior vena cava (SVC), near its junction with the right atrium (RA), is considered the ideal location for the central venous catheter tip to ensure proper function and prevent injuries. We determined catheter insertion depth with a new formula using the sternoclavicular joint and the carina as radiological landmarks, with a 1.5 cm safety margin. The accuracy of tip positioning with the radiological landmark-based technique (R) and Peres' formula (P) was compared using transoesophageal echocardiography. METHODS: Real-time ultrasound-guided central venous catheter insertion was done through the right internal jugular or subclavian vein. Patients were randomly assigned to either the P group (n=93) or the R group (n=95). Optimal catheter tip position was considered to be within 2 cm above and 1 cm below the RA-SVC junction. Catheter tip position, abutment, angle to the vascular wall, and flow stream were evaluated on a bicaval view. RESULTS: The distance from the skin insertion point to the RA-SVC junction and determined depth of catheter insertion were more strongly correlated in the R group [17.4 (1.2) and 16.7 (1.5) cm; r=0.821, P<0.001] than in the P group [17.3 (1.2) and 16.4 (1.1) cm; r=0.517, P<0.001], with z=3.96 (P<0.001). More tips were correctly positioned in the R group than in the P group (74 vs 93%, P=0.001). Abutment, tip angle to the lateral wall >40°, and disrupted flow stream were comparable. CONCLUSIONS: Catheter tip position was more accurate with a radiological landmark-based technique than with Peres' formula. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp KCT0001937.

Association between a non-synonymous HSD17B4 single nucleotide polymorphism and meat-quality traits in Berkshire pigs.

Single nucleotide polymorphisms (SNPs) are useful genetic markers that allow correlation of genetic sequences with phenotypic traits. It is shown here that HSD17B4, a bifunctional enzyme mediating dehydrogenation and anhydration during ß-oxidation of long-chain fatty acids, contains a non-synonymous SNP (nsSNP) of chr2:128,825,976A>G, c.2137A>G, I690V, within the sterol carrier protein-2 domain of the HSD17B4 gene, by RNA-Seq of liver RNA. The HSD17B4 mRNA was highly expressed in the kidney and liver among various other tissues in four pig breeds, namely, Berkshire, Duroc, Landrace, and Yorkshire. The nsSNP was significantly associated with carcass weight, backfat thickness, and drip loss (P < 0.05). Furthermore, HSD17B4 may play a crucial role during the early stages of myogenesis when expression of its mRNA was significantly high. In conclusion, HSD17B4 may serve as a possible regulator of muscle development, and its identification should help to select for improved economic traits of Berkshire pigs such as carcass weight, backfat thickness, and drip loss.

Unstable intertrochanteric versus displaced femoral neck fractures treated with cementless bipolar hemiarthroplasty in elderly patients; a comparison of 80 matched patients.

BACKGROUND: While hemiarthroplasty (HA) is considered the treatment of choice for displaced femoral neck (FN) fractures in elderly patients, HA has been partly performed as an alternative treatment option for unstable intertrochanteric (IT) fractures. However, there is a paucity of data regarding the risk and availability of HA for unstable IT fractures compared to HA for displaced FN fractures in elderly patients. Therefore, we performed this case-control study to determine whether HA for unstable IT fractures provides clinical results and survival comparable to HA for displaced FN fractures in elderly patients. HYPOTHESIS: HA for unstable IT fractures in elderly patients provides clinical results and 1-year survival comparable to HA for displaced FN fractures in the same aging group. MATERIALS AND METHODS: We identified 80 patients aged 75years or older, who underwent cementless bipolar HA for unstable IT fracture (AO/OTA type 31-A2.2/3 and A3.3). Their clinical results and 1-year survival were compared to the matched control group of 80 patients with displaced FN fractures (Garden type 3 and 4) treated with the same procedure. Perioperative results, postoperative complications, and 1-year survival were investigated between the two groups. Functional outcome was assessed by walking status and Harris hip score (HHS) 6months after surgery. RESULTS: Operating time was significantly longer in the IT group than the FN group (97.3min [50 to 255] vs. 79.3min [40 to 175], P=0.016). However, the two groups did not significantly differ regarding perioperative results, such as total blood loss, transfusion, intraoperative fracture, length of hospital stay, and postoperative complication. No statistically significant differences in walking status and HHS were observed between the groups. No significant difference in cumulative survival was observed between the two groups (P=0.836), with a 1-year survival rate of 80% (95% confidence interval [CI], 71.8 to 87.5) in the IT group and 82% (95% CI, 73.1 to 89.4) in the FN group. CONCLUSION: HA for unstable IT fractures in elderly patients showed clinical results and 1-year survival comparable to HA as the treatment of choice for displaced FN fractures in the same aging group. LEVEL OF EVIDENCE: Level III, case-control study.

Antibacterial activities of penicillic acid isolated from Aspergillus persii against various plant pathogenic bacteria.

UNLABELLED: The emergence of pathogenic bacterial strains resistant to agrochemicals and the increasing demand for organic foods have led to the discovery of new antibacterial metabolites that can be used either directly or as a lead molecule for development of synthetic bactericides. During the screening of antibacterial fungal cultures, we found that one fungal strain, Aspergillus persii EML-HPB1-11, showed strong in vitro antibacterial activity against Xanthomonas arboricola pv. pruni (Xap) with a minimum inhibitory concentration (MIC) of 10% of fermentation broth filtrate. The active compound was identified as penicillic acid (PA: 3-methoxy-5-methyl-4-oxo-2,5-hexadienoic acid) by mass and NMR spectroscopy. The in vitro antibacterial activity of PA was tested against 12 phytopathogenic bacteria. All of the bacterial pathogens tested were highly inhibited by PA with MIC values of 12·3-111·1 µg ml(-1) . It also effectively suppressed the development of bacterial spot disease in detached peach leaves, showing control values of 82·4 and 94·1% at concentrations of 111·1 and 333·3 µg ml(-1) respectively. This is the first report on the production of PA by A. persii. This study suggests that PA can be used as a lead molecule for development of synthetic bactericides for control of various plant diseases. SIGNIFICANCE AND IMPACT OF THE STUDY: Penicillic acid (PA) produced by the seed-borne fungus Aspergillus persii EML-HPB1-11 showed antibacterial activity against various plant pathogenic bacteria. The compound effectively inhibited the growth of 12 plant pathogenic bacteria and successfully controlled bacterial spot disease on peach leaf. These results suggest that PA can be used as a lead molecule for development of synthetic agrochemicals to control plant bacterial diseases.

Influence of arm position on catheter placement during real-time ultrasound-guided right infraclavicular proximal axillary venous catheterization.

BACKGROUND: Real-time ultrasound-guided infraclavicular proximal axillary venous catheterization is used in many clinical situations and provides the advantages of catheter stabilization, a reduced risk of catheter-related infection, and comfort for the patient without limitation of movement. However, unintended catheter tip dislocation and accidental arterial puncture occur occasionally. This study was designed to investigate the influence of arm position on catheter placement and complications. METHODS: Patients were randomized to either the neutral group (n=240) or the abduction group (n=241). In the neutral group, patients were positioned with the head and shoulders placed in an anatomically neutral position and the arms kept by the side during catheterization. In the abduction group, the right upper arm was abducted at 90° from the trunk during catheterization. After real-time ultrasound-guided catheterization was carried out in the right infraclavicular proximal axillary vein, misplacement of the catheter and all complications were evaluated with ultrasound and chest radiography. RESULTS: The success rate of complete catheterization before evaluating the placement of the catheter was high in both groups (97.1 vs 98.8%, P=not significant). The incidence of accidental arterial puncture was not different (1.7 vs 0%, P=not significant). The incidence of misplacement of the catheter was higher in the neutral group than in the abduction group (3.9 vs 0.4%, P=0.01). There were no complications, such as haemothorax, pneumothorax, or injury to the brachial plexus and phrenic nerve, in either group. CONCLUSIONS: Upper arm abduction may minimize the risk of misplacement of the catheter during real-time ultrasound-guided infraclavicular proximal axillary venous catheterization. CLINICAL TRIAL REGISTRATION: The trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001417.

Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

OBJECTIVE: To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS: Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS: Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION: The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

Anti-transforming growth factor ß-induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis.

AIM: Sepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor ß-induced protein (TGFBIp) is an extracellular matrix protein expressed by human endothelial cells and platelets that induces sepsis through interaction with integrin αvß5. The aim of this study was to investigate the role of TGFBIp in vascular permeability and the underlying mechanisms using TGFBIp-neutralizing antibody. METHODS: Mice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti-TGFBIp antibody (300 µg kg(-1), intravenously). Wild-type or integrin ß5-null mice received TGFBIp (0.1 mg kg(-1), intravenously) or were subjected to CLP. Human umbilical vein endothelial cells were exposed to lipopolysaccharide (100 ng mL(-1)) with or without neutralizing anti-TGFBIp antibody (50 µg mL(-1)). RESULTS: Administration of neutralizing anti-TGFBIp antibody in mice attenuated CLP-induced secretion of TGFBIp, leucocyte migration and vascular permeability and reduced septic mortality. Injected TGFBIp did not enhance vascular barrier permeability or leucocyte migration in ß5-null mice. Finally, neutralizing anti-TGFBIp antibody inhibited the specific interactions between TGFBIp and its receptor, integrin αvß5. CONCLUSION: Our findings demonstrate that treatment with a TGFBIp-neutralizing antibody can ameliorate the deleterious effects of sepsis.

OGA heterozygosity suppresses intestinal tumorigenesis in Apc(min/+) mice.

Emerging evidence suggests that aberrant O-GlcNAcylation is associated with tumorigenesis. Many oncogenic factors are O-GlcNAcylated, which modulates their functions. However, it remains unclear how O-GlcNAcylation and O-GlcNAc cycling enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), affect the development of cancer in animal models. In this study, we show that reduced level of OGA attenuates colorectal tumorigenesis induced by Adenomatous polyposis coli (Apc) mutation. The levels of O-GlcNAcylation and O-GlcNAc cycling enzymes were simultaneously upregulated in intestinal adenomas from mice, and in human patients. In two independent microarray data sets, the expression of OGA and OGT was significantly associated with poor cancer-specific survival of colorectal cancer (CRC) patients. In addition, OGA heterozygosity, which results in increased levels of O-GlcNAcylation, attenuated intestinal tumor formation in the Apc(min/+) background. Apc(min/+) OGA(+/-) mice exhibited a significantly increased survival rate compared with Apc(min/+) mice. Consistent with this, Apc(min/+) OGA(+/-) mice expressed lower levels of Wnt target genes than Apc(min/+). However, the knockout of OGA did not affect Wnt/ß-catenin signaling. Overall, these findings suggest that OGA is crucial for tumor growth in CRC independently of Wnt/ß-catenin signaling.