Risk factors, diagnosis, and updated classification of hepatorenal syndrome / 临床肝胆病杂志

Hepatorenal syndrome (HRS) is a common complication of decompensated cirrhosis and is traditionally defined as progressive oliguria or anuria, azotemia, dilutional hyponatremia, and hyponatremia, while renal insufficiency without marked organic lesions in the kidney is the typical manifestation of HRS. Recent studies have found that besides the abnormalities in hemodynamics, inflammatory response, oxidative stress, and direct renal tubular toxicity of bile salts are jointly involved in the development and progression of HRS. HRS is not the only renal complication in patients with liver cirrhosis, and it is only a functional form of acute kidney injury (AKI). HRS meeting the criteria for AKI is called HRS-AKI, which is formerly known as HRS-Ⅰ type. For cirrhotic patients with acute kidney disease or chronic kidney disease, if they meet the criteria for HRS, they can be diagnosed with HRS-NAKI, which is formerly known as HRS-Ⅱ type. The most common risk factors for HRS are infection, digestive bleeding, and large-volume paracentesis without transfusion of human serum albumin for volume expansion.

Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor and orexin-B receptor messenger ribonucleic acid expression and represses mitogen-activated protein kinase signaling / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypocretin (HCRT) signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy. Our previous study showed that xingshentongqiao decoction (XSTQ) is clinically effective for the treatment of narcolepsy. To determine whether XSTQ improves narcolepsy by modulating HCRT signaling, we investigated its effects on SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1 [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved in these processes were also assessed.</p><p><b>METHODS</b>The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays. OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis. Western blotting for mitogen-activated protein kinase (MAPK) pathway activation was performed to further assess the signaling mechanism of XSTQ.</p><p><b>RESULTS</b>XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells. This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).</p><p><b>CONCLUSIONS</b>XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells. XSTQ also promotes OX1R and OX2R expression. These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways. These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation, which may explain its ability to treat narcolepsy.</p>

Inhibitory effect of vasostatin on migration of pancreatic cancer endothelial cells / 中华胰腺病杂志

ObjectiveTo investigate the effect of vasostatin on the migration of pancreatic cancer endothelial cells.Methods Ad-vasostatin with different concentrations of vasostatin was used to transfect pancreatic cancer endothelial cells.Ad-LacZ transfection and PBS was used as control.The effect of vasostatin gene mediated by adenovirus on the migration of pancreatic cancer endothelial cells was measured by woundhealing assay,transwell migration assay,and tube formation assay.ResultsThe scratched lines in PBS group and Ad-LacZ group were almost healed 48 hours later,while the lines in Ad-vasostatin group were rarely healed.At the MOI of 1,2,5,the migration rate of Ad-Laz group was ( 84.7 ± 2.6) ％,(80.7 ± 1.7 ) ％ and (81.3±4.0)％,while the corresponding values were (77.7 ±2.1)％,(67.3 ±2.1)％ and (38.8 ±2.1 ) ％ in Ad-vasostatin group.Transwell migration assay indicated that the number of migrated cells in Advasostatin group was inhibited in a dose-dependant manner,at the MOI of 5,the migration became significantly decreased (F=180.88,P ＜0.05).At the MOI of 1,5,10,the number of tubes in Ad-LacZ group was 118±6,120±6 and 82±5,while the corresponding values were 65±4,21±4 and 4 ±1 in Ad-vasostatin group.The number of tubes of pancreatic cancer endothelial cells was inhibited by Ad-vasostatin in a dose-dependant manner,at the MOI of 10, it was difficult to form the tubes (F-300.85,P＜0.05). Conclusions The vasostatin gene mediated by adenovirus has a significant inhibitory effect on the migation of pancreatic cancer endothelial cells in vitro in a dose-dependent manner.

Relationship between deficits of learning and memory and expressions of PSD-95 in hippocampus in traumatic brain injury rats / 中华创伤杂志

ObjectiveTo investigate the relation of learning and memory with the expression of postsynaptic density 95 (PSD-95) in traumatic brain injury (TBI) rats in Morris water maze.Methods Forty adult male Sprague-Dawley rats were randomly assigned to the TBI group and control group.The TBI group was produced using the impact acceleration injury model.Morris water maze memory paradigm was used to assess the learning and memory function in both groups one week after injury.Protein electro-phoresis was used to observe the expression of PSD-95 1,3,7 d after TBI.ResultsCompared with the control group,the TBI group showed a longer latency in the Morris water maze after one week,significantly longer than the latency in the first three days after TBI.The quantification of PSD-95 in the hippocampus was gradually reduced at one week after TBI ( P ＜ 0.01 ).ConclusionTBI may decrease expression of PSD-95 in the hippocampus of the rats,as may be one of the mechanisms for impairments of learning and memory of rats.

Cyclooxygenase-2 inducingangiogenesis in pancreatic carcinoma is mediated by prostaglandin E_2 / 中华消化杂志

Objective To investigate the effects of cyclooxygenase-2 (COX-2) on the expressions of vascular endothelial growth factor (VEGF) and prostaglandin E_2 (PGE_2) in pancreatic carcinoma both in vitro and in vivo, and to clarify the possible mechanism of PGE_2 in mediating COX-2 inducing angiogenesis of pancreatic carcinoma. Methods In vitro study, the inhibitory effects of Celebrex, a selective cyclooxygenase-2 inhibitor, on the expression of VEGF and PGE_2 in pancreatic carcinoma cell lines PC-3 were determined using either enzyme-linked immuno-absorbent assay (ELISA) or radioimmunoassay (RIA). Effect of exogenous PGE_2 on the down-regulation of VEGF by Celebrex was also assessed. In vivo study, PC-3 cell line xenograft nude mice model was established. Changes of VEGF expression and PGE_2 of tumor tissues after the treatment of Celebrex were investigated using Western blotting or RIA. Results Celebrex suppressed the expressions of VEGF and PGE_2 in cultured PC-3 cell line with a manner of dose- and time-dependence. Exogenous PGE_2 up-regulated the expression of VEGF, which was suppressed by Celebrex in a dose-dependent fashion. In vivo study, administration of Celebrex into xenograft nude mice inhibited expressions of VEGF and PGE_2 significantly. Conclusion COX-2 is involved in angiogenesis in pancreatic carcinoma probably through the inhibition of the production of angiogenic factors such as VEGF. PGE_2 is likely to act as an important mediator in this process.

Roles of nuclear factor-?B in the development of rat pancreatic fibrosis mediated by angiotensin II / 中国病理生理杂志

AIM: To determine the effects of NF-?B on the development of rat pancreatic fibrosis mediated by angiotensin II. METHODS: Spraque-Dawley rats (200-300g) were randomly divided into normal group, control group and losartan-treatment group. Pancreatic fibrosis was induced by injection of 2% TNBS into biliopancreatic duct. Rats in losartan-treatment group and control group were respectively treated with losartan (10 mg?kg~(-1)?d~(-1)) by gavage and the same volume of saline vehicle. The expression, distribution, and activation of NF-?B were studied by Western blot, immunohistochemistry and TransAM~(TM). Toluidine blue staining and transmission electron microscopy were also used to observe the number, distribution and degranulation of mast cells. In addition, RT-PCR was performed to detect the intrapancreatic ICAM-1 mRNA expression. RESULTS: The expression and activity of intrapancreatic NF-?B p65 protein were significantly increased on day 3 after operation, reaching peak on day 7 [(0.406?0.086) mg/g total protein]. Mast cell activation was observed and ICAM-1 mRNA levels on day 3 and 7 were up-regulated in control group. Losartan treatment inhibited NF-?B expression and activation, reduced mast cell infiltration and degranulation and decreased ICAM-1 mRNA expression compared with control rats. CONCLUSION: It might be associated with the expression and activation of NF-?B that angiotensin II mediates inflammation and fibrosis in the early stage of pancreatic fibrosis. [

Regulation of angiogenesis by peroxisome proliferator-activated receptor-?in pancreatic carcinoma and its possible mechanisms / 中华消化杂志

Objective To explore the role of peroxisome proliferator activated receptor ?(PPAR ?) in angiogenesis in human pancreatic carcinoma with reference to the regulation of vascular endothelial growth factor (VEGF). Methods Expression of PPAR ? in SW1990 pancreatic carcinoma cells was examined by RT PCR and immunocytochemical staining. Secretion of VEGF by SW1990 cells, treated by 15 deoxy delta(12,14) prostaglandin J 2(15d PGJ 2), the ligand of PPAR ? and, 9 cis retinoic acid(9 cis RA) the ligand of retinoic X receptor(RXR)?, at different concentrations and durations, was detected by semi quantitative RT PCR. Effects of Rosiglitazone, a selective PPAR ? activator, on the changes of microvascular density (MVD) and VEGF expression were investigated in 30 SW1990 cell xenografted nude mice, among which 15 were in the treatment group (drank a solution of Rosiglitazone at the dose of 10 ?mol?kg -1 ?d -1 ) and 15 in the control group. Neovasculature was detected using immunohistochemistry staining labeled with anti Ⅳ collagen antibody and indicated by MVD. Results RT PCR and immunocytochemical staining showed that PPAR ? mRNA and protein were expressed in the SW1990 cell line. Semi quantitative RT PCR demonstrated that the combination of 15d PGJ 2 and 9 cis RA had a potent inhibitory effect on the expression of VEGF in SW1990 cells in both dose and time dependent manners. In vivo study, the MVD was statistically decreased in Rosiglitazone treated mice (10.67?3.07) compared with that in the control group (31.44?6.06) ( P

Regulation of PPAR? on the growth of pancreatic carcinoma is partly dependent on NF-?B and AP-1 / 中国病理生理杂志

AIM: To examine the effects of PPAR? activation on the growth of human pancreatic carcinoma in vitro and to explore the role of NF-?B and activator protein-1 (AP-1) in this process. METHODS: SW-1990 pancreatic cancer cells were treated with ligand of RXR?, 9-cis-RA, ligand of PPAR?, 15d-PGJ_2, and both. Antiproliferative effect was evaluated by using MTT assay; the expression of NF-?B p65 active protein was assayed by using TransAM~TM technique. Expression of c-jun and c-fos by SW1990 cells, which were treated with 15d-PGJ_2, 9-cis-RA and both at varying concentrations, were detected by RT-PCR. RESULTS: MTT assay demonstrated that 15d-PGJ_2, 9-cis-RA and the combination of both had a potent inhibitory effect on the growth of SW1990 cells in a dose-dependent manner. 9-cis-RA had a synergic action with 15d-PGJ_2 on the growth inhibition of pancreatic carcinoma. TransAM~TM showed a down-regulation trend of P65 active protein in SW1990 cells treated with 15d-PGJ_2, 9-cis-RA and both. RT-PCR demonstrated that the expression of c-jun mRNA in 15d-PGJ_2, 9-cis-RA and the combination of both-treated cells were firstly increased and then decreased, the expression of c-fos was decreased in 15d-PGJ_2 or 9-cis-RA treated SW1990 cells, but increased in cells treated with both 15d-PGJ_2 and 9-cis-RA. CONCLUSION: Activation of PPAR? exerts a negative regulatory effect on the growth of pancreatic carcinoma in vitro. Activation of RXR? has a synergic action with PPAR? agonist. The mechanism is probably associated with down-regulating the expression of NF-?B and AP-1. [