Inhibition of ASM activity ameliorates DSS-induced colitis in mice.

Acid sphingomyelinase (ASM) is a membrane lipid hydrolase, acting to generate ceramide and regulate cell functions and inflammatory responses.The roles of ASM in mediating T cell functions are postulated whereas its function in regulation of macrophages remains uncertain. The study was performed to explore ASM activity in control of macrophage functions.

Inhibition of NADPH oxidase activities ameliorates DSS-induced colitis.

NADPH oxidases (NOX) act to generate reactive oxygen species (ROS) and exhibit microbicidal bioactivity, whereas their roles in mediating immune responses of inflammation in intestine remain to be further elucidated. The study was performed to explore the effects of NOX activity on regulation of macrophage functions. Macrophage responses were induced by lipopolysaccharides (LPS) in RAW 264.

Advances in treatment of ulcerative colitis with herbs: from bench to bedside.

Ulcerative colitis (UC), an idiopathic inflammatory disorder in the colon, has become a clinical challenge, owing to the increasing incidence and poor prognosis. The conventional treatments for UC including aminosalicylates, corticosteroids, and immunosuppressants, induce remission in only half of patients. Meanwhile, the treatments often come with serious side effects which can be life-threatening.

Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells.

Aim: To investigate the effects of osteopontin (OPN) gene expression knockdown on colon cancer Lovo cells in vitro.

Methods: Four candidate small interfering RNA (siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC-siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector. After confirmation by restriction enzyme digestion and DNA sequencing, the recombinant plasmids were subsequently transfected into a human colon cancer cell line (Lovo) using a liposome transfection method.

[Effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma cells in vitro].

Objective: To investigate the effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma AGS cells.

Methods: With experiment-control system of the wild-type CagA positive strain and isogenic CagA negative mutant strain of Helicobacter pyroli (Hp) were used as control and experimental groups, respectively. The cell contact, migration and invasion were examined by light and electron microscopy and invasion assay.

Basic research on inflammatory bowel disease in China.

Objective: Since the etiology and the pathogenesis of inflammatory bowel disease (IBD) are still not well known, research on IBD often focuses on these topics. Investigative science papers about IBD in Chinese medical journals from 1989 to 2003 were viewed to understand the progress of basic IBD research in China.

Materials And Methods: The basic science investigative papers about IBD from 1989 to 2003 in Chinese periodicals (VIP and CMCC) were reviewed and analyzed; the key words used were as follows: inflammatory bowel disease, ulcerative colitis, Crohn's disease, basic science investigation, and literature review.

Novel analogs of D-e-MAPP and B13. Part 2: signature effects on bioactive sphingolipids.

Novel isosteric analogs of the ceramidase inhibitors (1S,2R)-N-myristoylamino-phenylpropanol-1 (d-e-MAPP) and (1R,2R)-N-myristoylamino-4'-nitro-phenylpropandiol-1,3 (B13) with modified targeting and physicochemical properties were developed and evaluated for their effects on endogenous bioactive sphingolipids: ceramide, sphingosine, and sphingosine 1-phosphate (Cer, Sph, and S1P) in MCF7 cells as determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Time- and dose-response studies on the effects of these compounds on Cer species and Sph levels, combined with structure-activity relationship (SAR) data, revealed 4 distinct classes of analogs which were predominantly defined by modifications of the N-acyl-hydrophobic interfaces: N-acyl-analogs (class A), urea-analogs (class B), N-alkyl-analogs (class C), and omega-cationic-N-acyl analogs (class D). Signature patterns recognized for two of the classes correspond to the cellular compartment of action of the new analogs, with class D acting as mitochondriotropic agents and class C compounds acting as lysosomotropic agents.

Novel analogs of D-e-MAPP and B13. Part 1: synthesis and evaluation as potential anticancer agents.

A series of novel isosteric analogs of the ceramidase inhibitors, (1S,2R)-N-myristoylamino-phenylpropanol-1 (d-e-MAPP) and (1R,2R)-N-myristoylamino-4'-nitro-phenylpropandiol-1,3 (B13), with modified targeting and physicochemical properties were designed, synthesized, and evaluated as potential anticancer agents. When MCF7 cells were treated with the analogs, results indicated that the new analogs were of equal or greater potency compared to the parent compounds. Their activity was predominantly defined by the nature of the modification of the N-acyl hydrophobic interfaces: N-acyl analogs (class A), urea analogs (class B), N-alkyl analogs (class C, lysosomotropic agents), and omega-cationic-N-acyl analogs (class D, mitochondriotropic agents).

Blockade of STAT3 by antisense oligonucleotide in TNBS-induced murine colitis.

Background And Aims: The expression of signal transducers and activators of transcription 3 (STAT3) is increased in Crohn's disease (CD), and nuclear translocated STAT3 is also found in the disease. However, the role of STAT3 protein on the pathogenesis of CD is not clear. This study was executed to investigate the role of STAT3 protein on the pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis, the pathogenesis of which is CD-like.

Diallyl trisulfide inhibits tumor necrosis factor-alpha expression in inflammed mucosa of ulcerative colitis.

The present study aimed to investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor (TNF)-alpha expression in inflammed mucosa of ulcerative colitis and its possible mechanism. Colonic biopsies from ulcerative colitis were treated with 0, 1, 5, and 10 microM DATS for 24 hr. Lactate dehydrogenase (LDH) activities and concentrations of TNF-alpha in supernatants were measured.

[Activation of nuclear factor-kappa B and expression of cytokine in intestinal epithelia stimulated by TNF-alpha].

Objective: To investigate the effect of nuclear factor-kappa B activation on proinflammatory cytokine expression in intestinal epithelia when intestinal epithelia are in inflammatory condition.

Methods: Colonic adenocarcinoma HT29 cells were cultured in wells and TNF-alpha (10 ng/ml) was added into half of the wells. The supernatants were collected and measured for IL-8 after 3 hours, nuclear factor-kappaB (NF-kappaB) P65 and IL-8 mRNA were also examined by Western blotting and RT-PCR respectively.

Imrecoxib: a novel and selective cyclooxygenase 2 inhibitor with anti-inflammatory effect.

Aim: To investigate the inhibitory effect of imrecoxib, a synthetic compound of completely new structure, on cyclooxygenase 1 (COX-1) and 2 (COX-2) and its anti-inflammatory effect in vivo.

Methods: The inhibitory effects of imrecoxib on cyclooxygenase 1 and 2 were studied using whole cell assay with murine peritoneal macrophages induced by calcimycin and LPS. The inhibitory effects of imrecoxib on mRNA level of COX-1 and COX-2 in human macrophage cell line U937 were detected by reverse transcription polymerase chain reaction (RT-PCR) analysis.

Probiotics inhibit TNF-alpha-induced interleukin-8 secretion of HT29 cells.

Aim: To study the effect of probiotics on interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines.

Methods: Colonic adenocarcinoma HT29 cells were cultured and divided into four groups: control, TNF-alpha (group T in short), bifidobacterium (group B), lactobacillus (group L). B.

Inhibitory effect of 3,4-diaryl-3-pyrrolin-2-one derivatives on cyclooxygenase 1 and 2 in murine peritoneal macrophages.

Aim: To develop a whole-cell assay based on murine peritoneal macrophages and evaluate the inhibitory effect of candidate compounds on cyclooxygenase-1 (COX-1) and COX-2.

Methods: Macrophages were stimulated with calcimycin or lipopolysaccharide (LPS) for various periods. Their abilities to convert endogenous arachidonic acid to 6-keto-PGF1alpha or PGE2 were examined by radioimmunoassay (RIA).