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Biomedical subjects

Jie-Shou Li

Publications and source records attributed to Jie-Shou Li.

At least 19 recordsLinked to original sources

Triptolide suppresses IL-1beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts.

AIM: To examine the inhibitive effects of triptolide on the expression of IL-8, monocyte chemotactic protein (MCP)-1, and matrix metalloproteinases (MMP)-3 in subepithelial myofibroblasts (SEMF) stimulated with IL-1beta. METHODS: SEMF cultures were established from normal colons in patients who underwent gut resection for colorectal carcinoma. Chemokine and MMP-3 expressions were determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of I kappa B-alpha(p-I kappa B-alpha) was determined by Western blotting. The DNA binding capacity of NF-kappa B was evaluated by electrophoretic mobility shift assays. RESULTS: IL-1beta stimulated protein and mRNA expression of IL-8, MCP-1, and MMP-3 in SEMF. Triptolide inhibited these effects of IL-1beta in a dose-dependent manner. Mechanistic studies revealed that triptolide markedly decreased IL-1beta -induced NF-kappa B DNA binding capacity and cytosolic amount of p-I kappa B-alpha. These results showed that triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF through the NF-kappa B pathway. CONCLUSION: Triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of I kappa B-alpha.

Anti-Inflammatory Agents, Non-Steroidal↗

Apoptosis and functional changes of dipeptide transporter (PepT1) in the rat small intestine after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can induce significant alterations of intestinal mucosal structure and barrier function. However, it has not been investigated whether, and to what degree, apoptosis and alterations of absorptive function in the intestinal mucosal epithelium occur after TBI. MATERIAL AND METHODS: Male Wistar rats were randomly divided into seven groups (five rats each group) including normal group, control group with sham operation, and TBI groups at hours 3, 12, 24, and 72, and on day 7. Parietal brain contusion was adopted using weight-dropping method. Intestinal mucosal structure was examined using histomorphmetric study and electron microscopy, and apoptosis was detected by TUNEL method. An everted sleeve of intestine was securely incubated in Kreb's solution with radioactive dipeptide ((3)H-Gly-Sar, 10 microCi/mL) to measure the uptake and transport of PepT1 of small intestinal epithelial cells. RESULTS: The villous height, crypt depth and surface area were significantly decreased at 24 h after TBI, and further declined to the degree of mucosal atrophy on day 7 after TBI. Apoptotic changes of condensed nuclei in epithelial cells and fractured, distorted, and sparse microvilli were found by electron microscopy. The number of apoptotic cells in the mucosal epithelium was significantly increased since 3 h after TBI, peaked at 72 h post-injury, then declined at 7 days, but was still higher than that of control. There was a highly negative relation between the apoptotic index and the villous height, the crypt depth, and villous surface area. Compared with that of normal and control rats, the transport and uptake of dipeptide was significantly increased at 3 h post-injury (P < 0.01), peaked at 12 h and declined a bit at 24 h post-injury, and returned to the level of normal and control rats at 72 h and 7 days. CONCLUSIONS: It is highly suggested that intestinal mucosa apoptosis plays an important role in the pathogenesis of acute gut damage after TBI. Intestinal PepT1 expression could be up-regulated after traumatic brain injury, and maintained the normal level under the condition of serious intestinal damage. Up-regulation of PepT1 may adaptively improve absorption of di- and tripeptides, independent of changes in the mucosal surface area.

Adaptation, Physiological↗

[Correlation of growth hormone receptor expression to preoperative radiosensitivity of rectal cancer patients].

BACKGROUND & OBJECTIVE: Growth hormone (GH) could activate pathways involved in DNA repair process by binding to growth hormone receptor (GHR), which is thought as one of the mechanisms of radioprotection. This study was to evaluate the correlation of GHR expression to radiosensitivity of rectal cancer. METHODS: The expression of GHR in biopsy specimens from 98 rectal cancer patients before preoperative irradiation and postoperative specimens was detected by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Radiosensitivity was evaluated according to Rectal Cancer Regression Grading. RESULTS: IHC revealed that GHR overexpression was positively correlated to poor response to radiotherapy (P<0.001, rs=0.399); RT-PCR also showed that radiosensitivity was significantly higher in GHR mRNA-negative group than in GHR mRNA-positive group (P<0.001, rs=0.398). Compared with the biopsy specimens before preoperative irradiation, the paired postoperative specimens showed significantly increased GHR expression in residual cancer cells (P<0.001). CONCLUSION: Detection of GHR expression before preoperative irradiation may predict radiosensitivity of rectal cancer.

Adult↗

Role of laparoscopic subtotal cholecystectomy in the treatment of complicated cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the "gold standard" in treating benign gallbladder diseases. Increasing laparoscopic experience and techniques have made laparoscopic subtotal cholecystectomy (LSC) a feasible option in more complex procedures. In recent years, few studies with a few cases of LSC have reported good results in patients with various types of cholecystitis. This study was designed to evaluate the feasibility, indications, characteristics and benefits of LSC in patients with complicated cholecystitis. METHODS: Altogether, 3485 patients were scheduled to receive LC during the past 4 years at our institute. Among them, 168 patients with various complicated forms of cholecystitis were treated by LSC. Meanwhile, the other 3317 patients who received standard LC were enrolled as the control group. Perioperative data from the two groups were collected and retrospectively analyzed. RESULTS: In the LSC group, 135 patients suffered from acute calculic cholecystitis, 18 from chronic calculic cholecystitis with cirrhotic portal hypertention, and 15 from chronic calculic atrophy cholecystitis with severe fibrosis. These patients constituted 4.8% of the total patients who underwent LC (168/3485) in the same period at our institute. In 122 patients, the cystic duct and artery were clipped before division. In another 46 patients, the gallbladder was initially incised at Hartmann's pouch. Five patients (3.0%) were converted to open subtotal cholecystectomy. The median operation time for LSC was 65.5 +/- 15.2 minutes, estimated operative blood loss was 71.5+/-15.5 ml, and the time to resume diet was 20.4 +/- 6.3 hours. Thirteen patients (7.7%) had local complications. The mean postoperative hospital stay was 4.2 +/- 2.6 days. In the LC group, 2887 had chronic calculic cholecystitis, 312 had acute calculic cholecystitis, 47 had chronic calculic atrophy cholecystitis, and 71 had polypus. Seventeen patients (0.5%) were converted to open cholecystectomy. The median operation time was 32.6 +/- 10.2 minutes, the estimated operative blood loss was 24.5 +/- 8.5 ml, and the time to resume diet was 18.3 +/- 4.5 hours. Thirty-nine patients (1.2%) had local complications. Mean postoperative hospital stay was 3.8 +/- 1.4 days. There was no bile duct injury or mortality in either group. CONCLUSIONS: LSC for patients with complicated cholecystitis is difficult, with a longer operation time, more operative blood loss and higher conversion and complication rates than LC. However, it is feasible and relatively safe. LSC is advantageous over open surgery, but it remains a non-routine choice. It is important to know the technical characteristics of LSC, and pay attention to perioperative bleeding and bile leak.

Adolescent↗

Non-composite combined liver and intestinal allotransplantation.

BACKGROUND: Patients with short bowel syndrome may require combined liver and intestinal transplantation due to total parenteral nutrition(TPN)-related liver damage. We report combined liver and intestinal allotransplantation as a non-composite technique in a patient in China. METHODS: During the operation, a 380 cm long intestine was transplanted with systemic drainage and aortic inflow, while the liver graft was placed in a piggyback fashion. Warm ischemic time of the donor graft was 2 minutes and 30 seconds, and cold ischemic time for intestinal and the liver graft was 6 hours and 40 minutes and 8 hours and 7 minutes, respectively. Immunosuppressants used after operation included tacrolimus, methylprednisolone, mycophenolate mofetil and Zenapax. RESULTS: The recipient recovered with no evidence of rejection and was kept well on tube feeding. Eventually, he died of massive hemorrhage of the thoracic cavity on day 210 after transplantation. CONCLUSION: The non-composite combined liver and intestinal allotransplantation is superior to composite technique in adult patients, particularly those who have had abdominal infection or repeated abdominal operations.

Adult↗

[Mechanism of reduction of albumin expression induced by lipopolysaccharide in rat hepatocytes].

BACKGROUND: The severity of hypoalbuminemia has been shown to be related to morbidity and mortality in some critical illnesses, illustrating the need for better understanding of molecular mechanism of hypoalbuminemia. Lipopolysaccharide (LPS) is a key mediator inducing hypoalbuminemia in sepsis and septic shock. The present study was designed to identify if the reduction of albumin expression is directly induced by LPS and modulated by activated extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in rat hepatocytes. METHODS: Primary rat hepatocytes were divided into five groups. In two of them, hepatocytes were treated with normal saline or 1 microg/ml LPS, then albumin mRNA expression was observed at 0, 2, 8, 12 and 24 hours after treatment. In another group, hepatocytes were pretreated with 100, 40 or 20 micromol/L of cycloheximide (CHX, an inhibitor of protein synthesis) for 30 minutes followed by 1 microg/ml LPS for 24 hours. Then the RNA was extracted from the cells for RT-PCR to detect the expression of albumin. The other two groups were administered 1 micromol/L, 10 micromol/L and 50 micromol/L of SB203580 (p38 MAPK inhibitor) or PD98059 (ERK inhibitor) 30 minutes prior to 1 microg/ml LPS treatment. After 24 hours of LPS treatment, the supernatant was collected and assayed for albumin concentrations. Data were analyzed by one-way analysis of variance, followed by the Newman-Keul test; a P<0.05 was considered significant. RESULTS: There was no marked change in albumin mRNA expression in the control group during 24-hours treatment with normal saline. The reduction did not occur until 24 hours after LPS treatment, and albumin mRNA decreased by 30% approximately compared to the control group at 24 hours (0.587 vs 0.832, P=0.007). CHX could inhibit the decline of albumin mRNA induced by LPS and the effect was correlated with the dose of CHX. The ERK inhibitor PD98059 caused a significant increase in LPS-induced albumin production at the three concentrations (119.7, 111.4 and 80.0 ng/ml vs 44.4 ng/ml, P=0.0013, 0.0025 and 0.009, respectively), whereas SB203580 obviously blocked albumin reduction in LPS-treated cells at the concentrations of 10 and 50 micromol/L (87.5 and 93.6 ng/ml vs 44.4 ng/ml, P=0.0076 and 0.0049, respectively). CONCLUSIONS: LPS can induce the reduction of albumin expression by new synthesized proteins indirectly, and the process may be related to the signal proteins of ERK and p38 kinase. The ERK and p38 kinase are critical signaling pathways in LPS-induced hypoalbuminemia which is worthwhile to understand in studying the molecular mechanism of hypoalbuminemia in sepsis and septic shock.

Albumins↗

Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock.

AIM: To investigate IL-1beta+3 594 in the 5th intron, IL-10-1 082 and CD14-159 polymorphisms in patients with acute pancreatitis (AP) and septic shock. METHODS: The study included 215 patients (109 with acute severe pancreatitis (SAP), 106 with acute mild pancreatitis (MAP)) and 116 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of PCR products. RESULTS: The frequencies of IL-1beta+3 594T, IL-10-1082G and CD14-159T allele were similar in patients with mild or severe pancreatitis and in controls. Within SAP patients, no significant differences were found in the allele distribution examined when etiology was studied again. Patients with septic shock showed a significantly higher prevalence of IL-10-1082G allele than those without shock (chi2= 5.921, P = 0.015). CONCLUSION: IL-10-1082G plays an important role in the susceptibility of SAP patients to septic shock. Genetic factors are not important in determination of disease severity or susceptibility to AP.

Acute Disease↗

Protective effect of L-arginine preconditioning on ischemia and reperfusion injury associated with rat small bowel transplantation.

AIM: To investigate the protective effect and possible mechanism of L-arginine preconditioning on ischemia and reperfusion injury associated with small bowel transplantation (SBT). METHODS: Male inbred Wistar rats weighting between 180 and 250 g were used as donors and recipients in the study. Heterotopic rat SBT was performed according to the techniques of Li and Wu. During the experiment, intestinal grafts were preserved in 4 degrees Ringer's solution for 8 h before being transplanted. Animals were divided into three groups. In group 1, donors received intravenous L-arginine (50 mg/kg, 1 mL) injection 90 min before graft harvesting. However, donors in control group were given normal saline (NS) instead. In group 3, six rats were used as sham-operated control. Specimens were taken from intestinal grafts 15 min after reperfusion. Histological grading, tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed. The graft survival of each group was monitored daily until 14 d after transplantation. RESULTS: Levels of MDA and MPO in intestine of sham-operated rats were 2.0+/-0.22 mmol/g and 0.66+/-0.105 U/g. Eight hours of cold preservation followed by 15 min of reperfusion resulted in significant increases in tissue MDA and MPO levels. Pretreatment with L-arginine before graft harvesting resulted in lower enhancement of tissue levels of MDA and MPO and the differences were significant (4.71+/-1.02 mmol/g vs 8.02+/-3.49 mmol/g, 1.03+/-0.095 U/g vs 1.53+/-0.068 U/g, P<0.05). Besides, animals in L-arginine pretreated group had better histological structures and higher 2-wk graft survival rates comparing with that in NS treated group (3.3+/-0.52 vs 6+/-0.1, 0/6 vs 6/6, P<0.05 or 0.01). CONCLUSION: L-arginine preconditioning attenuates ischemia and reperfusion injury in the rat SBT model, which was due to antioxidant activities partially.

Animals↗

Design of cervical pedicle locator and three-dimensional location of cervical pedicle.

STUDY DESIGN: To develop a high-accuracy, easy-manipulated, and low-cost cervical pedicle three-dimensional locator for guiding cervical pedicle screw placement. OBJECTIVES: To improve the safety of cervical pedicle screw insertion, simplify its manipulation, and offer safety guarantees in clinical application. SUMMARY OF BACKGROUND DATA: Because of the complicacy of the anatomic structure of cervical pedicle, clinical application of cervical pedicle screw remained hard to popularize. And recent advances on cervical pedicle location did not simplify the manipulation of procedure significantly. Without aid of locator, distance and angle errors were difficult to control. So far, the only instrument for the location of pedicle "computer-assisted image-guided surgical system" is too expensive for clinical use. Furthermore, it has not yet been documented on location instrument for insertion of cervical pedicle screws. METHODS: The high-accuracy three-dimensional locator, made of stainless steel was designed to aid cervical pedicle nail placement. The cadavers were inserted nails under guidance of the locator that has been input the corresponding parameters collected from CT images. Results were evaluated by CT scans. RESULTS: A total of 90 nails were inserted into cervical pedicles, 90% of which were found right in the pedicles; 10% had pedicle cortex breaches. Parallel offset error of the locator in cross-sectional and lateral CT image that was 0.56 +/- 0.70 and 1.04 +/- 0.99; angular offset error was 1.69 +/- 2.41 and 6.54 +/- 7.08. CONCLUSION: Three-dimensional locator of cervical pedicle and its localization technique achieved good results for individuated screws insertion into cervical pedicles, having such advantages as easy manipulation, high accuracy, and low cost. The system presented safety guarantee to the application and advanced the prevalence of pedicle techniques. Its principium and design were demonstrated feasible.

Bone Screws↗

A randomized controlled trial of laparoscopic versus open cholecystectomy in patients with cirrhotic portal hypertension.

AIM: To evaluate the characters, risks and benefits of laparoscopic cholecystectomy (LC) in cirrhotic portal hypertension (CPH) patients. METHODS: Altogether 80 patients with symptomatic gallbladder disease and CPH, including 41 Child class A, 32 Child class B and 7 Child class C, were randomly divided into open cholecystectomy (OC) group (38 patients) and LC group (42 patients). The cohorts were well-matched for number, age, sex, Child classification and types of disease. Data of the two groups were collected and analyzed. RESULTS: In LC group, LC was successfully performed in 36 cases, and 2 patients were converted to OC for difficulty in managing bleeding under laparoscope and dense adhesion of Calot's triangle. The rate of conversion was 5.3%. The surgical duration was 62.6+/-15.2 min. The operative blood loss was 75.5+/-15.5 mL. The time to resume diet was 18.3+/-6.5 h. Seven postoperative complications occurred in five patients (13.2%). All patients were dismissed after an average of 4.6+/-2.4 d. In OC group, the operation time was 60.5+/-17.5 min. The operative blood loss was 112.5+/-23.5 mL. The time to resume diet was 44.2+/-10.5 h. Fifteen postoperative complications occurred in 12 patients (30.0%). All patients were dismissed after an average of 7.5+/-3.5 d. There was no significant difference in operation time between OC and LC group. But LC offered several advantages over OC, including fewer blood loss and lower postoperative complication rate, shorter time to resume diet and shorter length of hospitalization in patients with CPH. CONCLUSION: Though LC for patients with CPH is difficult, it is feasible, relatively safe, and superior to OC. It is important to know the technical characters of the operation, and pay more attention to the meticulous perioperative managements.

Adult↗

Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats.

AIM: Nuclear factor kappa B (NF-kappaB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-kappaB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-kappaB activation and ICAM-1 expression following TBI. METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-kappaB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. RESULTS: There was a very low NF-kappaB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-kappaB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-kappaB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-kappaB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-kappaB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.

Animals↗

Amelioration of hemodynamics and oxygen metabolism by continuous venovenous hemofiltration in experimental porcine pancreatitis.

AIM: To investigate the potential role of continuous venovenous hemofiltration (CVVH) in hemodynamics and oxygen metabolism in pigs with severe acute pancreatitis (SAP). METHODS: SAP model was produced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight (BW)) and trypsin (2 U/kg BW). Animals were allocated either to untreated controls as group 1 or to one of two treatment groups as group 2 receiving a low-volume CVVH (20 mL/(kg.h)), and group 3 receiving a high-volume CVVH (100 (mL/kg.h)). Swan-Ganz catheter was inserted during the operation. Heart rate, arterial blood pressure, cardiac output, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, central venous pressure, systemic vascular resistance, oxygen delivery, oxygen consumption, oxygen extraction ratio, as well as survival of pigs were evaluated in the study. RESULTS: Survival time was significantly prolonged by low-volume and high-volume CVVHs, which was more pronounced in the latter. High-volume CVVH was significantly superior compared with less intensive treatment modalities (low-volume CVVH) in systemic inflammatory reaction protection. The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by intensive CVVH (87.4+/-12.5 kPa vs 116.3+/-7.8 kPa, P<0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in cardiac output, an attenuated decrease in systemic vascular resistance and an elevation in oxygen extraction ratio. CONCLUSION: CVVH blunts the pancreatitis-induced cardiovascular response and increases tissue oxygen extraction. The high-volume CVVH is distinctly superior in preventing sepsis-related hemodynamic impairment.

Acute Disease↗

Expressions of intestinal NF-kappaB, TNF-alpha, and IL-6 following traumatic brain injury in rats.

BACKGROUND: NF-kappaB regulates a large number of genes involved in the inflammatory response to critical illness, but it is not well known if and how NF-kappaB is activated in the gut following traumatic brain injury (TBI) and what is the role of cytokine-mediated inflammation in the pathogenesis of acute gut mucosal injury. MATERIALS AND METHODS: Male Wistar rats were randomly divided into control and TBI groups, each of which was subgrouped at hours 3, 12, 24, and 72 and on day 7. Parietal brain contusion was produced by a free-falling weight on the exposed dura of the right parietal lobe. NF-kappaB binding activity in jejunal tissue was measured using EMSA and the concentrations of TNF-alpha and IL-6 were detected using ELISA. RESULTS: NF-kappaB binding activity in the jejunum was significantly increased at 3 h following TBI, was maximal at 72 h, and remained elevated by 7 days postinjury. TNF-alpha and IL-6 concentrations were also significantly increased by 3 h postinjury, but peaked at 24 h and remained elevated on Day 7 postinjury. CONCLUSIONS: TBI induced a rapid and persistent up-regulation of NF-kappaB and proinflammatory cytokines in the gut, which may play an important role in the pathogenesis of acute gut mucosal injury mediated by inflammation.

Acute Disease↗

Change of the growth hormone-insulin-like growth factor-I axis in patients with gastrointestinal cancer: related to tumour type and nutritional status.

Changes in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis, especially acquired GH resistance, develop in many severe illnesses, including cachexia. To study changes in the GH-IGF-I axis in patients with cancer cachexia, biochemical markers and body composition parameters were measured in eighty-eight gastric cancer patients, thirty colorectal cancer patients (subclassified according to the presence or absence of cachexia) and twenty-four healthy control subjects. Fifty-nine patients were defined as cachectic, based on the percentage of weight loss compared with their previous normal weight. The remaining fifty-nine patients were defined as non-cachectic. Measurements were repeated in twenty-seven patients (sixteen with gastric cancer and eleven with colorectal cancer) 3 months after radical operation. Compared with the controls, the cachectic gastric cancer patients had high GH levels (1.36 v. 0.32 ng/ml; P=0.001), a trend towards high IGF-I levels (223.74 v. 195.15 ng/ml; P=0.128 compared with non-cachectic patients) and a low log IGF-I/GH ratio (2.55 and 2.66 v. 3.00; P=0.002), along with a decreased BMI; the cachectic colorectal cancer patients showed the biochemical characteristics of acquired GH resistance: high GH (0.71 v. 0.32 ng/ml; P=0.016), a trend towards decreased IGF-I levels (164.18 v. 183.24 ng/ml; P=0.127) and a low log IGF-I/GH ratio (2.54 v. 2.99; P=0.005), with increased IGF-I levels following radical surgery (200.49 v. 141.91 ng/ml; P=0.046). These findings suggest that normal GH reaction and sensitivity occur in gastric cancer patients, controlled by nutritional status, whereas acquired GH resistance develops in cachectic colorectal cancer patients, which may be caused by tumour itself.

Adult↗

Small intestinal organoid-derived SP cells contribute to repair of irradiation-induced skin injury.

Side population (SP) cells, characterized by their ability to efflux the fluorescent dye Hoechst 33342, were isolated from the small intestine of mice. In the abdominal irradiation model, small intestinal organoid-derived SP (sioSP) cells from ROSA 26 mice were submucosally injected into the small intestinal of the irradiated C57BL/6 mice. In contrast to the control mice, mice receiving sioSP cell transplantation demonstrated far less skin injury. Most importantly, hairs in the irradiated body part of the transplanted mice almost remained black, whereas the counterpart in the control mice almost turned white. Histochemistry studies showed the donor cells gave rise to skin cells in the irradiated skin. Thus, our study demonstrated for the first time that stem cells from the small intestine can differentiate into skin cells under local cues and thus supports the theory of stem cell plasticity.

Animals↗

Effect of somatostatin versus octreotide on portal haemodynamics in patients with cirrhosis and portal hypertension.

OBJECTIVES: Elevated portal inflow is part of the pathogenesis of portal hypertension in patients with cirrhosis. Vasoactive substances appear to play a primary role in the regulation of portal flow. The aim of this study was to investigate the effects of somatostatin and octreotide on portal pressure and plasma levels of insulin-like growth factor (IGF-1), nitric oxide (NO), endothelin-1 (ET-1) and glucagon (GLU). METHODS: Portal pressures of 14 cirrhotic patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) were directly measured via a catheter placed in the portal vein. Portal pressure and IGF-1, NO, ET-1 and GLU plasma levels were determined at baseline, and at 8 h and 24 h after administration of somatostatin or octreotide via portal vein catheter in a randomized, double-blind, cross-over design. RESULTS: The average decrease in portal pressure after intravenous infusion of somatostatin and octreotide was 9.4 +/- 1.0 cmH2O and 5.0 +/- 1.0 cmH2O, respectively (P < 0.01). Plasma levels of GLU and IGF-1 decreased significantly 8 and 24 h after somatostatin and octreotide infusion (P < 0.05). However, there were no significant decreases in plasma NO or ET-1 levels. There was a significant difference between somatostatin and octreotide groups (P < 0.01). CONCLUSION: Both somatostatin and octreotide can significantly reduce portal pressure, although somatostatin is more potent than octreotide. The underlying mechanisms may involve inhibition of the secretion of GLU, IGF-1 and other hormones as well as a decrease in hepatic metabolism and portal inflow leading to a reduction in portal pressure.

Adult↗

Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model.

BACKGROUND: Nuclear factor kappa B (NF-kB), proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) are frequently upregulated in the injured brain after traumatic brain injury (TBI). However, the temporal pattern of upregulation is not well defined. AIMS: The current study was undertaken to investigate the temporal profile of the expression of NF-kB, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma of the rat brain. SETTINGS AND DESIGN: A rat model of cortical contusion was produced by a free-falling weight on the exposed dura of right parietal lobe. The rats were randomly divided into control group and TBI groups at hours 3, 12, 24 and 72, and on day 7. MATERIAL AND METHODS: NF-kB binding activity in the surrounding brain of injured area was studied by electrophoretic mobility shift assay (EMSA). The levels of TNF-alpha and IL-6 were detected using ELISA and ICAM-1 expression studied by immunohistochemistry. STATISTICAL ANALYSIS: The data were analyzed by one-way ANOVA followed by Student-Newman-Keuls post hoc test. Relation between variables was analyzed using bivariate correlation with two-tailed test. RESULTS: Compared with that of control group, NF-kB binding activity in the injured brain was significantly increased through 12 h and 7 days postinjury, with the maximum at 72 h. The concentrations of TNF-alpha and IL-6 in the injured brain were significantly increased from 3 h to 7 days and maximal at 24 h postinjury. The number of ICAM-1 immunostained microvessels was significantly increased in the injured brain from 24 h to 7 days postinjury, with its peak at 72 h. Concomitant upregulation of TNF-alpha, IL-6, ICAM-1 and the cytokine mediators NF-kB in the injured brain was observed in the injured brain after cortical contusion, and there was a highly positive relation among these variables. CONCLUSIONS: Cortical contusion trauma could induce a concomitant and persistent upregulation of NF-kB binding activity, TNF-alpha, IL-6 and ICAM-1 in the injured rat brain which might play a central role in the injury-induced immune response of brain.

Animals↗

Lipopolysaccharide decreasing albumin expression in rat hepatocytes.

BACKGROUND: The relations of the severity of hypoalbuminemia to morbidity and mortality of patients with critical illness illustrate the need for better understanding of molecular mechanism of hypoalbuminemia. This study was undertaken to investigate the response of albumin synthesis to lipopolysaccharide (LPS)in rat hepatocytes in vitro in early acute phase of sepsis. METHODS: Hepatocytes were cultured at an initial cell density of 1.5 x 10(6) cells/well in 3 ml culture medium. There were two groups of samples which received either normal saline or 1 microg/L LPS randomly. Albumin mRNA in hepatocytes was assessed by reverse transcription-polymerase chain reaction (RT-PCR)and albumin level in the supernatant was measured by ELISA at 0, 2, 8, 12, 24 hours after exposure. Meanwhile, the albumin precursor was evaluated at the same time points by flow cytometry. RESULTS: The quantitative changes of mRNA,albumin precursor and its protein were analogous. All of them tended to decline at 12 hours post-treatment and did not decrease significantly until 24 hours after LPS exposure. Meanwhile, albumin mRNA decreased about 30% and the levels of albumin precursor and albumin reduced approximately 50%. CONCLUSIONS: LPS can inhibit albumin synthesis in rat hepatocytes by prevention of albumin transcription. Moreover, the response of hepatic albumin synthesis to LPS changes with the stage of sepsis process. The results show that albumin metabolism in sepsis is a complicated process and further studies are required to understand the molecular mechanism of LPS-induced hypoalbuminemia in sepsis.

Albumins↗