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| 1 | Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer显示文摘Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. | Jonathan Landy Emma Ronde Nick English Sue K Clark Ailsa L Hart Stella C Knight Paul J Ciclitira Hafid Omar Al-Hassi | 2016 | World Journal of Gastroenterology2016，22，11： | 39 |
| 2 | Esophageal motility abnormalities in gastroesophageal reflux disease显示文摘Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. | Irene Martinucci Nicola de Bortoli Maria Giacchino Giorgia Bodini Elisa Marabotto Santino Marchi Vincenzo Savarino Edoardo Savarino | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，2： | 24 |
| 3 | Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability显示文摘The integrity of the endothelial barrier is a determinant of the prognosis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, we investigated whether and how Sirtuin 1 (SIRT1) maintained the vascular integrity during ALI. An experimental model of ALI was established in mice through intratracheal administration of LPS (10 mg/kg). LPS stimulation significantly increased the pulmonary permeability and decreased the expression of SIRT1 and tight junction proteins (TJs), including occludin, claudin-5, tight junction protein 1 and tight junction protein 2. Morphological studies showed that LPS induced obvious lung injury with inammatory cell infiltration in the interstitial and alveolar space, hemorrhage, edema, and the thickened alveolar wall compared to the control mice. Intratracheal administration of the selective SIRT1 activator SRT1720 (6.25 mg/kg) significantly attenuated LPS- induced lung injury, lung hyper-permeability and increased TJs expression, whereas intratracheal administration of the selective SIRT1 inhibitor EX527 (6.25 mg/kg) aggravated LPS-induced ALI. Similar protective effects of SIRT1 on pulmonary cellular permeability were observed in primary human pulmonary microvascular endothelial cells treated with LPS (2 mg/mL) in vitro. We further demonstrated that the RhoA/ROCK signaling pathway was activated in SIRT1 regulation of tight junction permeability. The RhoA/ROCK inhibitor Y-27632 (10 μM) increased the expression of TJs and reversed LPS- or EX527-induced hyper-permeability. In conclusion, SIRT1 ameliorates LPS-induced lung injury via decreasing endothelial tight junction permeability, possibly via RhoA/ ROCK signaling pathway. This finding may contribute to the development of new therapeutic approaches for lung injury. | Cui-ping Fu Sheng-yu Hao Xiao-bo Xu Jian Zhou Zi-long Liu Huan Lu Li-min Wang Wei-zhong Jin Shan-qun Li | 2019 | Acta Pharmacologica Sinica2019，40，5： | 22 |
| 4 | Constraint-induced movement therapy enhances angiogenesis and neurogenesis after cerebral ischemia/reperfusion显示文摘Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke.In addition,it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling.Here,a stroke model was established by middle cerebral artery occlusion and reperfusion.Seven days after stroke,the following treatments were initiated and continued for 3 weeks:forced limb use in constraint-induced movement therapy rats(constraint-induced movement therapy group),intraperitoneal infusion of fasudil(a ROCK inhibitor)in fasudil rats(fasudil group),or lateral ventricular injection of NEP1-40(a specific antagonist of the Nogo-66 receptor)in NEP1-40 rats(NEP1-40 group).Immunohistochemistry and western blot assay results showed that,at 2 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK were lower in the ischemic boundary zone in rats treated with NEP1-40 compared with rats treated with ischemia/reperfusion or constraint-induced movement therapy alone.However,at 4 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK in the ischemic boundary zone were markedly decreased in the NEP1-40 and constraint-induced movement therapy groups,but there was no difference between these two groups.Compared with the ischemia/reperfusion group,modified neurological severity scores and foot fault scores were lower and time taken to locate the platform was shorter in the constraint-induced movement therapy and fasudil groups at 4 weeks after middle cerebral artery occlusion,especially in the constraint-induced movement therapy group.Immunofluorescent staining demonstrated that fasudil promoted an immune response of nerve-regeneration-related markers(BrdU in combination with CD31(platelet endothelial cell adhesion molecule),Nestin,doublecortin,NeuN,and glial fibrillary acidic protein)in the subventricular zone and ischemic boundary zone ipsilateral to the infarct.After 3 weeks of constraint-induced movement therapy,the number of regenerated nerve cells was noticeably increased,and was accompanied by an increased immune response of tight junctions(claudin-5),a pericyte marker(a-smooth muscle actin),and vascular endothelial growth factor receptor 2.Taken together,the results demonstrate that,compared with fasudil,constraint-induced movement therapy led to stronger angiogenesis and nerve regeneration ability and better nerve functional recovery at 4 weeks after cerebral ischemia/reperfusion.In addition,constraint-induced movement therapy has the same degree of inhibition of RhoA and ROCK as NEP1-40.Therefore,constraint-induced movement therapy promotes angiogenesis and neurogenesis after cerebral ischemia/reperfusion injury,at least in part by overcoming the Nogo-A/RhoA/ROCK signaling pathway.All protocols were approved by the Institutional Animal Care and Use Committee of China Medical University,China on December 9,2015(approval No.2015 PS326 K). | Zhi-Yong Zhai Juan Feng | 2019 | Neural Regeneration Research2019，14，10： | 22 |
| 5 | Electroacupuncture improves gut barrier dysfunction in prolonged hemorrhagic shock rats through vagus anti-inflammatory mechanism显示文摘AIM:To investigate whether electroacupuncture(EA)at Zusanli(ST36)prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism.METHODS:Sprague-Dawley rats were subjected to about 45%of total blood volume loss followed by delayed fluid replacement(DFR)with Ringer lactate 3h after hemorrhage.In a first study,rats were randomly divided into six groups:(1)EAN:EA at non-channel acupoints followed by DFR;(2)EA:EA at ST36 after hemorrhage followed by DFR;(3)VGX/EA:vagotomy(VGX)before EA at ST36 and DFR;(4)VGX/EAN:VGX before EAN and DFR;(5)α-bungarotoxin(α-BGT)/EA:intraperitoneal injection ofα-BGT before hemorrhage,followed by EA at ST36 and DFR;and(6)α-BGT/EAN group:α-BGT injection before hemorrhage followed by EAN and DFR.Survival and mean arterial pressure(MAP)were monitored over the next 12 h.In a second study,with the same grouping and treatment,cytokine levels in plasma and intestine,organ parameters,gut injury score,gut permeability to 4 kDa FITC-dextran,and expression and distribution of tight junction protein ZO-1 were evaluated.RESULTS:MAP was significantly lowered after blood loss;EA at ST36 improved the blood pressure at corresponding time points 3 and 12 h after hemorrhage.EA at ST36 reduced tumor necrosis factor-αand interleukin(IL)-6 levels in both plasma and intestine homogenates after blood loss and DFR,while vagotomy or intraperitoneal injection ofα-BGT before EA at ST36reversed its anti-inflammatory effects,and EA at ST36did not influence IL-10 levels in plasma and intestine.EA at ST36 alleviated the injury of intestinal villus,the gut injury score being significantly lower than that of EAN group(1.85±0.33 vs 3.78±0.59,P<0.05).EA at ST36 decreased intestinal permeability to FITCdextran compared with EAN group(856.95 ng/mL±90.65 ng/mL vs 2305.62 ng/mL±278.32 ng/mL,P<0.05).EA at ST36 significantly preserved ZO-1 protein expression and localization at 12 h after hemorrhage.However,EA at non-channel acupoints had no such effect,and abdominal vagotomy andα-BGT treatment could weaken or eliminate the effects of EA at ST36.Besides,EA at ST36 decreased blood aminotransferase,MB isoenzyme of creatine kinase and creatinine vs EAN group at corresponding time points.At the end of 12-h experiment,the survival rate of the EA group was significantly higher than that of the other groups.CONCLUSION:EA at ST36 attenuates the systemic inflammatory response,protects intestinal barrier integrity,improves organ function and survival rate after hemorrhagic shock via activating the cholinergic antiinflammatory mechanism. | Ming-Hua Du Hong-Min Luo Sen Hu Yi Lv Zhi-Long Lin Li Ma | 2013 | World Journal of Gastroenterology2013，19，36： | 21 |
| 6 | Arpin contributes to bacterial translocation and development of severe acute pancreatitis显示文摘AIM: To assess the impact of Arpin protein and tight junction(TJ) proteins in the intestinal mucosa onbacterial translocation in patients with severe acute pancreatitis(SAP).METHODS: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation(BT) in the blood [i.e., BT(+) and BT(-)].Twenty healthy individuals were included in the control group.BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting.RESULTS: Bacterial DNA was detected in the peripheral blood of 62.0% of patients(31/50) with SAP.The expression of TJ proteins in SAP patients was lower than that in healthy controls.In contrast, Arpin protein expression in SAP patients was higher than in healthy controls(0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05).Among SAP patients, those positive for BT showed a higher level of claudin-2 expression(0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin(OC)(0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1(0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT(-) patients.Moreover, the level of Arpin expression in BT(+) patients was higher than in BT(-) patients(0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05).CONCLUSION: Arpin protein affects the expression of tight junction proteins and may have an impact on BT.These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis. | Wen-Sheng Deng Jian Zhang Hui Ju Hong-Mei Zheng Jiang Wang Su Wang Dian-Liang Zhang | 2015 | World Journal of Gastroenterology2015，21，14： | 20 |
| 7 | Choledochal cysts: Similarities and differences between Asian and Western countries显示文摘Choledochal cysts(CCs)are rare bile duct dilatations,intra-and/or extrahepatic,and have higher prevalence in the Asian population compared to Western populations.Most of the current literature on CC disease originates from Asia where these entities are most prevalent.They are thought to arise from an anomalous pancreaticobiliary junction,which are congenital anomalies between pancreatic and bile ducts.Some similarities in presentation between Eastern and Western patients exist such as female predominance,however,contemporary studies suggest that Asian patients may be more symptomatic on presentation.Even though CC disease presents with an increased malignant risk reported to be more than 10%after the second decade of life in Asian patients,this risk may be overstated in Western populations.Despite this difference in cancer risk,management guidelines for all patients with CC are based predominantly on observations reported from Asia where it is recommended that all CCs should be excised out of concern for the presence or development of biliary tract cancer. | George N Baison Morgan M Bonds William S Helton Richard A Kozarek | 2019 | World Journal of Gastroenterology2019，25，26： | 16 |
| 8 | 在诊断 choledochal 包囊的磁性的回声 cholangiopancreatography 的角色: 盒子系列和评论显示文摘 AIM:To determine the merits of magnetic resonance cholangiopancreatography(MRCP) as the primary diagnostic test for choledochal cysts(CC’s).METHODS:Between 2009 and 2012,patients who underwent MRCP for perioperative diagnosis were identified.Demographic information,clinical characteristics,and radiographic findings were recorded.MRCP results were compared with intraoperative findings.A PubMed search identified studies published between 1996-2012,employing MRCP as the primary preoperative imaging and comparing results with either endoscopic retrograde cholangiopancreatography(ERCP) or operative findings.Detection rates for CC’s and abnormal pancreaticobiliary junction(APBJ) were calculated.In addition detection rates for clinically related biliary pathology like choledocholithiasis and cholangiocarcinomas in patients diagnosed with CC’s were also evaluated.RESULTS:Eight patients were identified with CC’s.Six patients out of them had typeⅣCC’s,1 had type I and 1 had a new variant of choledochal cyst with confluent dilatation of the common bile duct(CBD) and cystic duct.Seven patients had an APBJ and 3 of those had a long common-channel.Gallstones were found in 2 patients,1 had a CBD stone,and 1 pancreatic-duct stone was also detected.In all cases,MRCP successfully identified the type of CC’s,as well as APBJ with ductal stones.From analyzing the literature,we found that MRCP has 96%-100% detection rate for CC’s.Additionally,we found that the range for sensitivity,specificity,and diagnostic accuracy was 53%-100%,90%-100% and 56%-100% in diagnosing APBJ.MRCP’s detection rate was 100% for choledocholithiasis and 87% for cholangiocarcinomas with concurrent CC’s.CONCLUSION:After initial ultrasound and computed tomography scan,MRCP should be the next diagnostic test in both adult and pediatric patients.ERCP should be reserved for patients where therapeutic intervention is needed. | Vikas Y Sacher James S Davis Danny Sleeman Javier Casillas | 2013 | World Journal of Radiology2013，5，8： | 15 |
| 9 | Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage显示文摘Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage. | Hideki Kanamaru Hidenori Suzuki | 2019 | Neural Regeneration Research2019，14，7： | 15 |
| 10 | Transthoracic vs transhiatal surgery for cancer of the esophagogastric junction:A meta-analysis显示文摘AIM:To compare the efficacy and safety of the transthoracic and transhiatal approaches for cancer of the esophagogastric junction.METHODS:An electronic and manual search of the literature was conducted in PubMed,EmBase and the Cochrane Library for articles published between March1998 and January 2013.The pooled data included the following parameters:duration of surgical time,blood loss,dissected lymph nodes,hospital stay time,anastomotic leakage,pulmonary complications,cardiovascular complications,30-d hospital mortality,and long-term survival.Sensitivity analysis was performed by excluding single studies.RESULTS:Eight studies including 1155 patients with cancer of the esophagogastric junction,with 639 patients in the transthoracic group and 516 in the transhiatal group,were pooled for this study.There were no significant differences between two groups concerning surgical time,blood loss,anastomotic leakage,or cardiovascular complications.Dissected lymph nodes also showed no significant differences between two groups in randomized controlled trials(RCTs)and nonRCTs.However,we did observe a shorter hospital stay(WMD=1.92,95%CI:1.63-2.22,P<0.00001),lower30-d hospital mortality(OR=3.21,95%CI:1.13-9.12,P=0.03),and decreased pulmonary complications(OR=2.95,95%CI:1.95-4.45,P<0.00001)in the transhiatal group.For overall survival,a potential survival benefit was achieved for typeⅢtumors with the transhiatal approach.CONCLUSION:The transhiatal approach for cancers of the esophagogastric junction,especially typesⅢ,should be recommended,and its long-term outcome benefits should be further evaluated. | Ming-Tian Wei Yuan-Chuan Zhang Xiang-Bing Deng Ting-Han Yang Ya-Zhou He Zi-Qiang Wang | 2014 | World Journal of Gastroenterology2014，20，29： | 15 |
| 11 | Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1显示文摘AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxidative stress is mediated by H2O2.The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance(TER)and permeability was estimated by measuring the paracellular transport of FITC-labeled4-kDa dextran(FD4).The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux.The expression of tight junction(TJ)proteins was assessed using reverse-transcription polymerase chain reaction(RT-PCR)and immunofluorescence staining.RESULTS:Without H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced the mRNA expression of these TJ proteins.Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin.Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface.H2O2disrupted the integrity of claudin-1.Treatment with fucoidan dramatically attenuated the expression of claudin-1.CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1.Thus,fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases. | Atsushi Iraha Hiroshi Chinen Akira Hokama Takumi Yonashiro Tetsu Kinjo Kazuto Kishimoto Manabu Nakamoto Tetsuo Hirata Nagisa Kinjo Futoshi Higa Masao Tateyama Fukunori Kinjo Jiro Fujita | 2013 | World Journal of Gastroenterology2013，19，33： | 15 |
| 12 | Metal-organic framework coated titanium dioxide nanorod array p-n heterojunction photoanode for solar water-splitting显示文摘This paper presents a p-n heterojunction photoanode based on a p-type porphyrin metal-organic framework (MOF) thin film and an n-type rutile titanium dioxide nanorod array for photoelectrochemical water splitting. The TiO2@MOF core-shell n anorod array is formed by coati ng an 8 nm thick MOF layer on a vertically aligned TiO2 nanorod array scaffold via a layer-by-layer self-assembly method. This vertically aligned core-shell nanorod array enables a long optical path length but a short path length for extraction of photogenerated minority charge carriers (holes) from TiO2 to the electrolyte. A p-n junction is formed between TiO2 and MOF, which improves the extraction of photogenerated electr ons and holes out of the TiO2 nano rods. In additi on, the MOF coati ng sign ificantly improves the efficie ncy of charge in jecti on at the photoanode/electrolyte interface. Introduction of Co(lll) into the MOF layer further enhances the charge extraction in the photoanode and improves the charge injection efficiency. As a result, the photoelectrochemical cell with the TiO2@Co-MOF nanorod array photoanode exhibits a photocurrent density of 2.93 mA/cm^2 at 1.23 V (vs. RHE), which is ~ 2.7 times the photocurrent achieved with bare T1O2 nanorod array under irradiation of an unfiltered 300 W Xe lamp with an output power density of 100 mW/cm^2. | Hui Yang Joeseph Bright Sujan Kasani Peng Zheng Terence Musho Banglin Chen Ling Huang Nianqiang Wu | 2019 | Nano Research2019，12，3： | 14 |
| 13 | Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract显示文摘Congenital abnormalities of the kidney and urinary tract(CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis(bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number(agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography(US) is typically the first imaging performed as it is easily available, noninvasive and radiation free used both antenatally and postnatally. Computed tomography(CT) and magnetic resonance imaging(MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. | Subramaniyan Ramanathan Devendra Kumar Maneesh Khanna Mahmoud Al Heidous Adnan Sheikh Vivek Virmani Yegu Palaniappan | 2016 | World Journal of Radiology2016，8，2： | 13 |
| 14 | Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3inflammasome activation in LPS-induced vascular injury显示文摘The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide(2 μg/mL) and administrated by 0.1–2 mmol/L aspirin. The wild type mice were stimulated with LPS(100 μg/kg/day), and 1 h later treated with aspirin(12.5, 62.5, or125 mg/kg/day) and dexamethasone(0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of theendothelial tight junction protein zonula occludens-1/2(ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome. | Xing Zhou Yanjiao Wu Lifeng Ye Yunting Wang Kaimin Zhang Lingjun Wang Yi Huang Lei Wang Shaoxiang Xian Yang Zhang Yang Chen | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 13 |
| 15 | Effects of rhein on intestinal epithelial tight junction in IgA nephropathy显示文摘AIM: To investigate the effects of rhein on intestinal epithelial tight junction proteins in rats with IgA nephropathy (IgAN). METHODS: Twenty-eight female Sprague-Dawley rats were randomly divided into four groups (7 per group): Control, IgAN, Rhein-treated, and Rheinprevented. Bovine serum albumin, lipopolysaccharide and CCl4 were used to establish the rat model of IgA nephropathy. The Rhein-treated group was given rhein from week 7 until the rats were sacrificed. The Rheinprevented group was given rhein from week 1. Animals were sacrificed at the end of week 10. We observed the changes in the intestinal epithelial tight junctions using transmission electron microscopy, and expression of intestinal epithelial tight junction proteins zona occludens protein (ZO)-1 and occludin by immunofluorescence using laser confocal microscopy. Changes in mRNA and protein expression of ZO-1 and occludin were measured by reverse transcriptase polymerase chain reaction and Western blotting. The ratio of urinary lactulose/mannitol was measured by high performance liquid chromatography (HPLC) for assessing the intestinal permeability. RESULTS: In the control group, the tight junctions lied between epithelial cells on the top of the outer side of the cell membrane, and appeared in dense dotted crystal structures, the neighboring cells were binded tightly with no significant gap, and the tight junction protein ZO-1 and occludin were evenly distributed in the intestinal epithelial cells at the top of the junction. Compared with the control group, in the IgAN group, the structure of the tight junction became obscured and the dotted crystal structures had disappeared; the fluorescence of ZO-1 and occludin was uneven and weaker (5.37 ± 1.27 vs 10.03 ± 1.96, P < 0.01; 4.23 ± 0.85 vs 12.35 ± 4.17, P < 0.01); the mRNA expression of ZO-1 and occludin decreased (0.42 ± 0.19 vs 0.92 ± 0.24, P < 0.01; 0.40 ± 0.15 vs 0.97 ± 0.25, P < 0.01); protein expression of ZO-1 and occludin was decreased (0.85 ± 0.12 vs 1.98 ± 0.43, P < 0.01; 0.72 ± 0.15 vs 1.38 ± 0.31, P < 0.01); and the ratio of urinary lactulose/mannitol increased (3.55 ± 0.68 vs 2.72 ± 0.21, P < 0.01). In the Rheinprevented and Rhein-treated groups, compared with the IgAN group, the intestinal epithelial tight junctions were repaired; fluorescence of ZO-1 and occludin was stronger (11.16 ± 3.52 and 8.81 ± 2.30 vs 5.37 ± 1.27, P < 0.01; 10.97 ± 3.40 and 9.46 ± 2.40 vs 4.23 ± 0.85, P < 0.01); mRNA of ZO-1 and occludin increased (0.81 ± 0.17 and 0.64 ± 0.16 vs 0.42 ± 0.19, P < 0.01; 0.82± 0.22 and 0.76 ± 0.31 vs 0.40 ± 0.15, P < 0.01); protein expression of ZO-1 and occludin was increased (2.07 ± 0.41 and 1.57 ± 0.23 vs 0.85 ± 0.12, P < 0.01; 1.34 ± 0.21 and 1.15 ± 0.17 vs 0.72 ± 0.15, P < 0.01); and the ratio of urinary lactulose/mannitol decreased (2.83 ± 0.43 and 2.87 ± 0.18 vs 3.55 ± 0.68, P < 0.01). CONCLUSION: Rhein can enhance the expression of ZO-1 and occludin, repair damaged tight junctions, and protect the intestinal barrier. | Sheng-Nan Peng Hui-Hong Zeng Ai-Xiang Fu Xiao-Wen Chen Qing-Xian Zhu | 2013 | World Journal of Gastroenterology2013，19，26： | 13 |
| 16 | Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion显示文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway. | Zuo-Yan Sun Fu-Jiang Wang Hong Guo Lu Chen Li-Juan Chai Rui-Lin Li Li-Min Hu Hong Wang Shao-Xia Wang | 2019 | Neural Regeneration Research2019，14，5： | 12 |
| 17 | Diet supplementation with an organic acids-based formulation affects gut microbiota and expression of gut barrier genes in broilers显示文摘This study was designed to study the effect of diet supplementation with an organic acids-based formulation(OABF) on luminal-and mucosa-associated bacteria, concentration of volatile fatty acids(VFA), microbial glycolytic enzyme activity and expression of mucin 2(MUC2), immunoglobulin A(IgA)and tight junction protein, i.e., zonula occludens-1(ZO1), zonula occludens-2(ZO2), claudin-1(CLDN1),claudin-5(CLDN5) and occludin(OCLN), genes at the ileal and cecal level. A 2 × 2 factorial design was used having OABF inclusion and avilamycin as main factors. Subsequently, 544 day-old male Cobb broilers were allocated in the following 4 treatments, each with 8 replicates: no additions(CON), 1 g OABF/kg diet(OA),2.5 mg avilamycin/kg diet(AV) and combination of OA and AV(OAAV). The trial lasted for 42 days. In the ileum, OAAV resulted in lower mucosa-associated total bacteria levels(PO × A= 0.028) compared with AV.In addition, ileal digesta levels of Clostridium perfringens subgroup were decreased by avilamycin(PA= 0.045). Inclusion of OABF stimulated the activity of microbial glycolytic enzymes, whereas avilamycin resulted in lower acetate(PA= 0.021) and higher butyrate(PA= 0.010) molar ratios. Expression of ZO1 and CLDN5 was down-regulated by both OABF(PO= 0.016 and PO= 0.003, respectively) and avilamycin(PA= 0.016 and PA= 0.001, respectively). In addition, CLDN1 was down-regulated in AV compared with CON(PO × A= 0.012). Furthermore, OABF down-regulated MUC2(PO= 0.027), whereas avilamycin down-regulated nuclear factor kappa B subunit 1(NFKB1)(PA= 0.024), toll-like receptor 2 family member B(TLR2B)(PA= 0.011) and toll-like receptor 4(TLR4)(PA= 0.014) expression. In the ceca, OABF inclusion increased digesta levels of Clostridium coccoides(PO= 0.018) and Clostridium leptum(PO= 0.040) subgroups, while it up-regulated MUC2 expression(PO= 0.014). Avilamycin(PA= 0.044) and interaction(PO × A< 0.001) effects for IgA expression were noted, with CON having higher IgA expression compared with AV. In conclusion, new findings regarding OABF inclusion effects on an array of relevant biomarkers for broiler gut ecology have been reported and discussed in parallel with avilamycin effects used as a positive control. This new knowledge is expected to provide a response baseline for follow up trials under various stress and challenge conditions. | Irida Palamidi Konstantinos C.Mountzouris | 2018 | Animal Nutrition2018，，4： | 11 |
| 18 | IUPU经腹腹腔镜联合膀胱软镜肾盂取石及肾盂成型术显示文摘1概述肾盂输尿管连接处梗阻(ureteropelvic junction obstruction,UPJO)是引起肾积水最常见的原因,它被定义为尿液从肾脏流入近端输尿管时出现梗阻的疾病。梗阻会造成肾盂内压增高、肾积水,进而导致肾功能损害,同时也会因尿液淤积引起肾结石[1,2]。当UPJO合并肾盂或肾盏结石时,选择何种恰当的治疗方式既能解决UPJO问题又能取出结石,同时最大程度的减少病人痛苦。 | 杨昆霖 李学松 周利群 | 2015 | 泌尿外科杂志(电子版)2015，7，3： | 11 |
| 19 | Total polysaccharides of the Sijunzi decoction attenuate tumor necrosis factor-α-induced damage to the barrier function of a Caco-2 cell monolayer via the nuclear factor-κB-myosin light chain kinase-myosin light chain pathway显示文摘AIM To explore the protective effects and underlying mechanisms of total polysaccharides of the Sijunzi decoction(TPSJ) on the epithelial barriers in vitro. METHODS Caco-2 cell monolayers were treated with or without TPSJ in the presence or absence of TNF-α, and paracellular permeability and transepithelial electrical resistance(TEER) were measured to evaluate the epithelial barrier function. Immunofluorescence and western blotting were respecti-vely used to evaluate the distribution and expression of the tight junction proteins claudin 1, claudin 2, zo3, and occludin in Caco-2 cells. western blotting was also used to evaluate the cellular expression of myosin light chain(MLC), phosphorylated MLC(pM LC), MLC kinase(MLCK), and nuclear factor(NF)-κB p65. RESULTS TPSJ promoted the proliferation of Caco-2 cells and inhibited TNF-α-induced secretion of pro-inflammatory cyto-kines. Furthermore, TPSJ significantly ameliorated both the reduction of TEER and the increased paracellular permeability observed in tumor necrosis factor(TNF)-α-damaged Caco-2 monolayers. Furthermore, TPSJ remarkably attenuated TNF-α-induced morphological changes, downregulated the expression of claudin 1, claudin 2, zo3, and occludin, and markedly suppressed TNF-α-mediated upregulation of p-MLC and MLCK expression. Finally, TPSJ inhibited the activation and expression of NF-κB p65. CONCLUSION Our results demonstrate that TPSJ alleviates the TNF-α-induced impairment of the intestinal epithelial cell barrier function by suppressing NF-κB p65-mediated phosphorylation of MLCK and MLC. | Yue Lu Leng Li Jin-wei Zhang Xiao-qin Zhong Jian-An wei Ling Han | 2018 | World Journal of Gastroenterology2018，24，26： | 10 |
| 20 | Clinical comparison of antrum-preserving double tract reconstruction vs roux-en-Y reconstruction after gastrectomy for Siewert types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction显示文摘AIM:To explore a reasonable method of digestive tract reconstruction,namely,antrum-preserving double-tract reconstruction(ADTR),for patients with adenocarcinoma of the esophagogastric junction(AEG) and to assess its efficacy and safety in terms of longterm survival,complications,morbidity and mortality.METHODS:A total of 55 cases were retrospectively collected,including 18 cases undergoing ADTR and 37 cases of Roux-en-Y reconstruction(RY) for AEG(Siewert types Ⅱ and Ⅲ) at North Sichuan Medical College. The cases were divided into two groups. The clinicopathological characteristics,perioperative outcomes,postoperative complications,morbidity and overall survival(OS) were compared for the two different reconstruction methods.RESULTS:Basic characteristics including sex,age,body mass index(BMI),Siewert type,p T status,p N stage,and lymph node metastasis were similar in the two groups. No significant differences were found between the two groups in terms of perioperative outcomes(including the length of postoperative hospital stay,operating time,and intraoperative blood loss) and postoperative complications(consisting of anastomosis-related complications,wound infection,respiratory infection,pleural effusion,lymphorrhagia,and cholelithiasis). For the ADTR group,perioperativerecovery indexes such as time to first flatus(P = 0.002) and time to resuming a liquid diet(P = 0.001) were faster than those for the RY group. Moreover,the incidence of reflux esophagitis was significantly decreased compared with the RY group(P = 0.048). The postoperative morbidity and mortality rates for overall postoperative complications and the rates of tumor recurrence and metastasis were not significantly different between the two groups. Survival curves plotted using the Kaplan-Meier method and compared by log-rank test demonstrated similar outcomes for the ADTR and RY groups. Multivariate analysis of significantly different factors that presented as covariates on Cox regression analysis to assess the survival and recurrence among AEG patients showed that age,gender,BMI,pleural effusion,time to resuming a liquid diet,lymphorrhagia and tumor-nodemetastasis stage were important prognostic factors for OS of AEG patients,whereas the selection of surgical method between ADTR and RY was shown to be a similar prognostic factor for OS of AEG patients.CONCLUSION:ADTR by jejunal interposition presents similar rates of tumor recurrence,metastasis and longterm survival compared with classical reconstruction with RY esophagojejunostomy; however,it offers considerably improved near-term quality of life,especially in terms of early recovery and decreased reflux esophagitis. Thus,ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types Ⅱ and Ⅲ AEG. | Jiang-Wei Xiao Zi-Lin Liu Peng-Cheng Ye Ya-Jun Luo Zhi-Ming Fu Qin Zou Shou-Jiang Wei | 2015 | World Journal of Gastroenterology2015，21，34： | 10 |
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