Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

Background/Aims: Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. Methods: Forty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. Results: Prevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. Conclusion IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

To analyze the correlation between lipid profile and disease activity in patients with inflammatory bowel disease (IBD).A total of 307 Crohn′s disease (CD) patients, 232 ulcerative colitis (UC) patients and 165 healthy subjects from the same geographic region were included. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a)[Lp(a)] were retrieved from their medical records. Crohn disease activity index (CDAI) and Mayo scores were calculated as measurement of disease severity for CD and UC separately. Patients with CD and UC had lower TC, TG, HDL-C and LDL-C levels than those in control group ( P<0.05). Additionally, CDAI was negatively associated with TC, HDL-C and LDL-C levels ( r=-0.218, -0.210, -0.176, P<0.05), while TG level was not associated with CDAI. Mayo scores was not significantly associated with TC, HDL-C, LDL-C and TG. Patients with CD had higher Lp(a) levels than those in UC and control group ( P<0.05). Furthermore, patients with active CD had higher Lp (a) levels than those with inactive disease ( P<0.05).The Lp(a) levels in CD patients were positively associated with CDAI ( r=0.151, P<0.05), while Lp(a) level in UC group was nor assocriated with Mayo score. Patients with IBD have dyslipidemia and lipid profile is associated with disease activity in CD patients.

Background/Aims: Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. Methods: Forty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. Results: Prevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. Conclusion IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

Objective:Mesenteric fat hypertrophy is present in about a quarter of Crohn′s disease (CD) patients and it can be easily detected by bowel ultrasound (US). The purpose of this research was to assess the correlation between mesenteric fat hypertrophy and behavior and activity of CD.Methods:A total of 89 CD patients who admitted to the First Affiliated Hospital of Nanjing Medical University from August 2018 to November 2019 were recruited in this study. The total CD patients were divided into two groups depending on with or without mesenteric fat hypertrophy by US tests. Crohn′s disease activity index (CDAI), simplified endoscopic score for Crohn′s disease (SES-CD), serum inflammatory indicators and fecal calprotectin were assessed.Results:Mesenteric fat hypertrophy was significantly associated with stricturing behavior (B2, P<0.01). CDAI ( P=0.002) , blood platelet ( P=0.001) , C-reactive protein ( P=0.024) , fecal calprotectin ( P=0.004) and bowel wall thickness ( P<0.01) in patients with mesenteric fat hypertrophy were significantly higher than those without, but not the erythrocyte sedimentation rate ( P=0.110) and SES-CD ( P=0.115) . Serum albumin ( P=0.001) in patients with mesenteric fat hypertrophy was lower than that in patients without mesenteric fat hypertrophy. Conclusion:Mesenteric fat hypertrophy is correlated with intestinal stenosis and disease activity in patients with Crohn′s disease.

A novel method was proposed for the quantification of nitrite ion in aqueous samples by the combination of an advanced quantitative fluorescence model with ratiometric fluorescence indicator 2 , 3-diaminonaphthalene . The proposed method was tentatively applied to direct quantitative determination of nitrite ion in turbid environmental water samples containing both scatterers and absorbers; and its performance was thoroughly investigated and evaluated. Experimental results showed that the proposed method could realize accurate quantitative determination of nitrite ion in environmental water samples with recovery rates in the range of 90. 8%-103. 0%, which were comparable to the corresponding values of HPLC-DAD experiments. The limit of detection and limit of quantification of the proposed method were estimated to be 1 . 9 and 5. 8 nmo/L, respectively.

Objective:To conduct a systematic study of the immunologic response of rats to transplanted glutaraldehyde ( GA)-treated porcine blood vessels in vivo.Methods: The experiment was divided into two groups:fresh group and glutaraldehyde-treated group.Twenty cases of fresh and glutaraldehyde-treated porcine pulmonary arteries were subcutaneously embedded in rats.We compared the changes using HE staining and immunohistochemistry.Results:HE staining showed that there were stronger expression on day 12 and day 30 in the fresh group than that in the glutaraldehyde group.There were similar results in morphology in CD68,C3,IgG.The results of integral optical density ( IOD) in immunohistochemistry showed that IOD started rising from day 4 and got the peak on day 12 or day 30 and or fell on day 60.Conclusion: Innate immunity played an important role in the research on xenogenic immunological rejection mechanism.The immunogenicity of glutaraldehyde-treated xenogenic blood vessels is lower than that in fresh blood vessels.However there is still immunogenicity in glutaraldehyde-treated xenogenic blood vessels.We will explore better ways to obviously weaken the rejection.

Objective To investigate the expression of insulin-like growth factor 2 receptor(IGF-2R)induced by hypoxia and serum deprivation(H/SD)in cultured neonatal rat cardiomyocytes in vitro.Methods Cultured neonatal rat cardiomyocytes were randomly divided into control group and H/SD group.Expression of IGF-2R mRNA was measured by RT-PCR and real time RT-PCR.Level of IGF-2R protein was measured by enzyme-linked immunosorbent assay(ELISA).Results Compared with control group,the expression of IGF-2R mRNA increased significantly (P ＜0.01)in cardiomyocytes cultured in H/SD condition for 12 h and 24 h,and IGF-2R protein was upregulated in cardiomyocytes cultured in H/SD condition for 24 h(P ＜0.05).Conclusion H/SD may induce IGF-2R expression,and IGF-2R may potentially explain the mechanism of cardiomyocyte damage induced by ischemia.