The homing and engraftment of hematopoietic stem cells (HSC) into bone marrow is the first critical step for successful clinical hematopoietic stem cell transplantation (HSCT). SDF-1 / CXCR4 is considered to be a very promising target to promote HSC homing. In recent years, with the in-depth research on the HSC homing, a variety of new strategies for promoting HSC homing and engraftment have been explored, such as nuclear hormone receptor, histone deacetylase inhibitor, prostaglandin and metabolic regulation, so as to increase the success rate of HSCT and improve the survival of patients. In this review, the recent research advances in the mechanism of HSC homing and strategies to promote HSC homing and engraftment were summarized and discussed.
Humans ; Hematopoietic Stem Cells/physiology* ; Bone Marrow ; Hematopoietic Stem Cell Transplantation ; Gene Expression Regulation ; Prostaglandins/metabolism*

OBJECTIVETo investigate the effect of seawater exposure on intestinal injury in rabbits with scald burns and explore the mechanisms.

METHODSSixty-three rabbits with scald burns covering 20% total body surface area were randomized equally into scald control group (group A), scald with freshwater exposure group (group B), and scald with seawater exposure group (group C). At 2, 4 and 8 h after scald burns, 7 rabbits from each group were sacrificed for detecting plasma superoxide dismutase (SOD) and lipid peroxide (LPO) levels and intestinal contents of prostaglandins (PGs) and for examining the intestinal pathologies; immunohistochemistry was used to detect the expression of Bax and Bcl-2 proteins in the small intestinal epithelium.

RESULTSThe rabbits in group C showed severer intestinal mucosal and barrier function damages than those in groups A and B. The plasma SOD activity and intestinal PGs contents were significantly lowered in group C than in groups A and B at 2, 4, and 8 h postburn (P<0.01) and reduced as the postburn time extended (P<0.01). In group C, plasma LPO content was the highest among the groups (P<0.01) and increased significantly with the seawater exposure time (P<0.01). The expression of Bax and Bcl-2 in the intestinal mucosal tissues was also the highest in group C (P<0.01) at 4 h and 8 h postburn and increased significantly with time (P<0.01).

CONCLUSIONSeawater exposure exacerbates scald burn-induced intestinal mucosal and barrier function damages in rabbits mainly by aggravating intestinal inflammation and structural damage, as evidenced by decreased intestinal PGs contents and plasma SOD activity, increased plasma PLO content, and enhanced Bax and Bcl-2 protein expressions in the intestinal mucosa.

Animals ; Burns ; pathology ; Intestinal Mucosa ; metabolism ; physiopathology ; Lipid Peroxidation ; Prostaglandins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rabbits ; Seawater ; adverse effects ; Soft Tissue Injuries ; Superoxide Dismutase ; blood ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDPulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD.

METHODSWe measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg.

RESULTSCompared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P < 0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P < 0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P < 0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P < 0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r = 0.477-0.589, P < 0.05).

CONCLUSIONThe increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Aged ; Breath Tests ; Female ; Humans ; Hypertension, Pulmonary ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Male ; Middle Aged ; Prostaglandins A ; blood ; metabolism ; Pulmonary Disease, Chronic Obstructive ; blood ; metabolism

OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.

METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).

RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).

CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

Astrocytes are the most abundant cells in the central nervous system that play roles in maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe complication of Plasmodium falciparum infection. Prostaglandin (PG) D2 is abundantly produced in the brain and regulates the sleep response. Moreover, PGD2 is a potential factor derived from P. falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme breakdown process to release iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites. Here, we showed that treatment of a human astrocyte cell line, CCF-STTG1, with PGD2 significantly increased the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that PGD2 treatment increased the level of HO-1 protein, in a dose- and time-dependent manner. Thus, PGD2 may be involved in the pathogenesis of cerebral malaria by inducing HO-1 expression in malaria patients.
Animals ; Astrocytes/*enzymology ; Blotting, Western ; Cell Line ; Gene Expression Profiling ; Heme Oxygenase-1/*biosynthesis ; Humans ; Malaria, Cerebral/*pathology ; Malaria, Falciparum/*complications/*pathology ; Plasmodium falciparum/*pathogenicity ; Prostaglandins/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo observe the effects of Herba dendrobii on rats with stomach-heat syndrome and to explore the mechanisms.

METHODRats were fed with decoction of Rhizoma Zingiberis for 15 continuous days to induce the model of stomach-heat syndrome. After modeling, Herba Dendrobii (HD) decoction were given (in the doses of 1.5, 0.75 g x kg(-1) respectively) for 10 days. After treatment, amount of the daily diet, volume and absorbance of urine, pellet number and moistness of excrement, color and coating degree of tongue were recorded; the body thermal effects were detected with thermal texture maps (TTM) system; the biochemical indexes of blood reflecting the physiological function of stomach, including thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha), motilin (MTL), gastrin (Gas), somatostation (SS), interleukin-4 (IL-4) and interleukin-8 (IL-8) were measured by radio immunoassay; and the histological changes of gastric mucosa were observed by hematoxylin-eosin (HE) stain.

RESULTThe model rat had yellow coating and red tongues (P < 0.05). The amount of daily diet were increased (over 10%), urine volume and excrement pellet number were decreased (over 10%). The their urine color became deep (P < 0.01) and their excrement became dry. The temperatures in head, neck, left fore-armpit, chest, up-abdomen, mid-abdomen of the model rats were raised up (difference > 0.5 degrees C or difference > 1.0 degree C ). The content of 6-keto-PGF1alpha in blood of model rats decreased evidently (P < 0.01), and the contents of MTL, Gas and IL-8 increased conspicuously (P < 0.01). The histological changes of gastric mucosa in the model rats were as follows: diffuse congestion, infiltration of neutrophil, less secretion, decrease of the number of chief and parietal cells, etc (P < 0. 05 or P < 0.01). After treatment with HD, except the daily food weight, the temperatures in head, neck and chest, the content of MTL and the number of chief cells, the other indexes observed above were improved noticeably (difference > 0.5 RC or difference > 1.0 degree C, P < 0.05 or P < 0.01).

CONCLUSIONThe reason why HD relieves the general symptom and sign the gastric mucosa of rats with stomach-heat syndrome is that HD can increase 6-keto-PGF1alpha and decrease IL-8, Gas, TXB2 in their blood.

Animals ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Gastric Dilatation ; drug therapy ; metabolism ; Gastrins ; Interleukin-4 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Motilin ; metabolism ; Prostaglandins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Detection, Psychological ; Signal Transduction ; drug effects ; Stomach Diseases ; drug therapy ; metabolism ; Syndrome ; Thromboxanes ; metabolism

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma.
Animals ; Anti-Infective Agents/pharmacology ; Asthma/*immunology/metabolism ; Cytokines/metabolism ; Histamine/metabolism ; Humans ; Hypersensitivity/*immunology/metabolism ; Immune System ; Immunoglobulin E/immunology ; Leukotrienes/metabolism ; Mast Cells/*cytology ; Mice ; Models, Biological ; Prostaglandins/metabolism ; Tumor Necrosis Factor-alpha/metabolism

Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Colonic Neoplasms/drug therapy/*etiology/prevention & control ; Cyclooxygenase 2/metabolism ; Cyclooxygenase Inhibitors/pharmacology/therapeutic use ; Humans ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/metabolism ; Prostaglandins/metabolism/*physiology

BACKGROUNDCyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.

METHODSFifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1alpha (6-K-PGF1alpha) contents were assessed.

RESULTSThirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P < 0.01 and P < 0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P < 0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1alpha concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P < 0.05 and P < 0.01 respectively), decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1alpha levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours (P < 0.05).

CONCLUSIONSAcute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.

Acute Disease ; Animals ; Colitis ; physiopathology ; Cyclooxygenase 2 ; physiology ; Hyperalgesia ; physiopathology ; Liver ; metabolism ; Liver Diseases ; physiopathology ; Male ; Morphine ; pharmacology ; Nitrobenzenes ; pharmacology ; Prostaglandins ; physiology ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; pharmacology

BACKGROUND/AIMS: Prostaglandin (PG) A2 has been reported to inhibit the growth of hepatocellular carcinoma cells via activation of apoptosis, although the molecular mechanisms involved have not been clarified, yet. To investigate the mechanism of the PGA2-induced apoptosis, we analyzed the activation of caspases during the apoptosis of hepatoma cell lines. METHODS: Induction of apoptosis by PGA2 in hepatoma cell lines, Hep 3B and Hep G2, was assessed by DAPI staining of nuclei and agarose gel electrophoresis of genomic DNA. The involvement of caspases was analyzed by immunoblot analysis of poly ADP-ribose polymerase (PARP) and by checking the effect of caspase inhibitors on PGA2-induced apoptosis. RESULTS: PGA2 inhibited the growth of Hep 3B and Hep G2 cells, accompanying nuclear condensation and fragmentation, and genomic DNA laddering, which are the hallmarks of apoptosis. The PARP was not cleaved during the apoptosis of Hep 3B and Hep G2 cells and caspase inhibitors such as z-VAD-Fmk and z-DEVD-Fmk exerted no effect on the PGA2-induced apoptosis. CONCLUSIONS: These results suggest that PGA2 induces apoptosis in Hep 3B and Hep G2 cells via caspase-independent pathway.
Apoptosis/*drug effects ; Carcinoma, Hepatocellular/*pathology ; Caspases/antagonists & inhibitors/*metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Enzyme Activation ; Humans ; Liver Neoplasms/*pathology ; Prostaglandins A/*pharmacology ; Research Support, Non-U.S. Gov't ; Tumor Cells, Cultured