|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Molecular mechanisms of liver ischemia reperfusion injury:Insights from transgenic knockout models显示文摘Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor grafts.The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis.Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury.IRI involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways.Transgenic animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies.Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein.This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI. | Gourab Datta Barry J Fuller Brian R Davidson | 2013 | World Journal of Gastroenterology2013，19，11： | 50 |
| 2 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 3 | Malignant biliary obstruction:From palliation to treatment显示文摘Malignant obstruction of the bile duct from cholan-giocarcinoma,pancreatic adenocarcinoma,or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery.The optimal treatment-including the decision whether to treat prior to resection-depends on the type of malignancy,as well as the stage of disease.Preoperative biliary drainage is generally discouraged due to the risk of infectious complications,though some situations may benefit.Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure.For pancreatic cancer patients,self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion.For cholangiocarcinoma patients,treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement,with less risk of infectious complications or failure.For patients of either malignancy who have advanced disease with palliative goals only,the choice of stent for endoscopic decompression depends on estimated survival,with plastic stents favored for survival of < 4 mo.New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor.Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction. | Brian R Boulay Aleksandr Birg | 2016 | World Journal of Gastrointestinal Oncology2016，8，6： | 24 |
| 4 | Management and prevention of acute and chronic lateral ankle instability in athletic patient populations显示文摘Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significantlong-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and nonanatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance. | Brendan J Mc Criskin Kenneth L Cameron Justin D Orr Brian R Waterman | 2015 | World Journal of Orthopedics2015，6，2： | 20 |
| 5 | Managing malignant biliary obstruction in pancreas cancer: Choosing the appropriate strategy显示文摘Most patients with pancreatic cancer develop malignant biliary obstruction.Treatment of obstruction is generally indicated to relieve symptoms and improve morbidity and mortality.First-line therapy consists of endoscopic biliary stent placement.Recent data comparing plastic stents to self-expanding metallic stents(SEMS)has shown improved patency with SEMS.The decision of whether to treat obstruction and the means for doing so depends on the clinical scenario.For patients with resectable disease,preoperative biliary decompression is only indicated when surgery will be delayed or complications of jaundice exist.For patients with locally advanced disease,self-expanding metal stents are superior to plastic stents for long-term patency.For patients with advanced disease,the choice of metallic or plastic stent depends on life expectancy.When endoscopic stent placement fails,percutaneous or surgical treatments are appropriate.Endoscopic therapy or surgical approach can be used to treat concomitant duodenal and biliary obstruction. | Brian R Boulay Mayur Parepally | 2014 | World Journal of Gastroenterology2014，20，28： | 18 |
| 6 | Evolving role of the endoscopist in management of gastrointestinal neuroendocrine tumors显示文摘Neuroendocrine tumors(NETs) are uncommon gastrointestinal neoplasms but have been increasingly recognized over the past few decades. Luminal NETs originate from the submucosa of the gastrointestinal tract and careful endoscopic exam is a key for accurate diagnosis. Despite their reputation as indolent tumors with a good prognosis,some NETs may have aggressive features with associated poor long-term survival. Management of NETs requires full understanding of tumor size,depth of invasion,local lymphadenopathy status,and location within the gastrointestinal tract. Staging with endoscopic ultrasound or cross-sectional imaging is important for determining whether endoscopic treatment is feasible. In general,small superficial NETs can be managed by endoscopic mucosal resection and endoscopic submucosal dissection(ESD). In contrast,NETs larger than 2 cm are almost universally treated with surgical resection with lymphadenectomy. For those tumors between 11-20 mm in size,careful evaluation can identify which NETs may be managed with endoscopic resection. The increasing adoption of ESD may improve the results of endoscopic resection for luminal NETs. However,enthusiasm for endoscopic resection must be tempered with respect for the more definitive curative results afforded by surgical treatment with more advanced lesions. | Cemal Yazici Brian R Boulay | 2017 | World Journal of Gastroenterology2017，23，27： | 9 |
| 7 | Neuroimaging the brain-gut axis in patients with irritable bowel syndrome显示文摘AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population. | Kristen R Weaver Lee Anne B Sherwin Brian Walitt Gail D'Eramo Melkus Wendy A Henderson | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，2： | 8 |
| 8 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 9 | Current protective strategies in liver surgery显示文摘During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection. | Kurinchi S Gurusamy Hector D Gonzalez Brian R Davidson | 2010 | World Journal of Gastroenterology2010，16，48： | 7 |
| 10 | Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications显示文摘AIM To investigate the additional clinical impact of hepatic ischaemia reperfusion injury(HIRI) on patients sustaining acute kidney injury(AKI) following liver transplantation.METHODS This was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation(OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT(> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration(CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase(AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor(< 1000 IU/L), moderate(1000-5000 IU/L) or severe(> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications(AKI and HIRI) alone and then as a combined outcome. RESULTS Out of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustainedmoderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively(P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation(P < 0.001) and intensive care length of stay(P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication(P = 0.049). CONCLUSION HIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI. | Suehana Rahman Susan V Mallett Brian R Davidson | 2017 | World Journal of Hepatology2017，9，18： | 6 |
| 11 | Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial显示文摘 | Stephen B Hanauer Brian G Feagan Gary R Lichtenstein Lloyd F Mayer S Schreiber Jean Frederic Colombel Daniel Rachmilewitz Douglas C Wolf Allan Olson Weihang Bao Paul Rutgeerts | 2002 | The Lancet2002，，9317： | 6 |
| 12 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 13 | Premotor biomarkers for Parkinson's disease-a promising direction of research显示文摘The second most serious neurodegenerative disease is Parkinson’s disease(PD).Over the past several decades,a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear.Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders,screen novel therapeutics,and predict eventual clinical PD before the onset of symptoms.Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area.Moreover,other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid,blood,or saliva.Finally,interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers.The current review highlights recent advances and underscores areas of potential advancement. | Brian R Haas Tessandra H Stewart Jing Zhang | 2012 | Translational Neurodegeneration2012，1，1： | 5 |
| 14 | Diagnostic and therapeutic endoscopic approaches to intraductal papillary mucinous neoplasm显示文摘Pancreatic cystic lesions are increasingly identified on routine imaging.One specific lesion,known as intraductal papillary mucinous neoplasm(IPMN),is a mucinous,pancreatic lesion characterized by papillary cells projecting from the pancreatic ductal epithelium.The finding of mucin extruding from the ampulla is essentially pathognomonic for diagnosing these lesions.IPMNs are of particular interest due to their malignant potential.Lesions range from benign,adenomatous growths to highgrade dysplasia and invasive cancer.These mucinous lesions therefore require immediate attention to determine the probability of malignancy and whether observation or resection is the best management choice.Unresected lesions need long-term surveillance monitoring for malignant transformation.The accurate diagnosis of these lesions is particularly challenging due to the substantial similarities in morphology of pancreatic cystic lesions and limitations in current imaging technologies.Endoscopic evaluation of these lesions provides additional imaging,molecular,and histologic data to aid in the identification of IPMN and to determine treatment course.The aim of this article is to focus on the diagnostic and therapeutic endoscopic approaches to IPMN. | Brian G Turner William R Brugge | 2010 | World Journal of Gastrointestinal Surgery2010，2，10： | 4 |
| 15 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 16 | Comparison of parametric and nonparametric models for traffic flow forecasting显示文摘 | Brian L Smith Billy M Williams R Keith Oswald | 2002 | Transportation Research Part C2002，，4： | 3 |
| 17 | Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury显示文摘AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoidal neutrophil adhesion in preconditioned animals(121.39 ± 30.65)(P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI(80.83 ± 13.03),RIPC + IR(17.35 ± 2.47),and PTDC+IR(11.66 ± 1.17) Zn PP + RIPC + IR(41.33 ± 3.07) reduced hepatocellular death. Zn PP significantly increased hepatocellular death(P < 0.05 PTDC/RIPC vs Zn PP and IR). The CINC cytokine levels in sham(101.32 ± 6.42). RIPC + sham(412.18 ± 65.24) as compared to sham(P < 0.05). Hepatic IR(644.08 ± 181.24)(P < 0.05). RIPC CINC-1 levels in the early phase(401.62 ± 78.56). And PDTC(HO inducer) CINC-1 levels in hepatic IR(413.36 ± 63.06) were significantly lower. HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels(521.81 ± 74.9)(P < 0.05). The serum CINC levels were high in the late phase of hepatic IR(15306 ± 1222.04). RIPC reduced CINC levels in the late phase of IR(467.46 ± 26.06),P < 0.05.CONCLUSION RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR. | Niteen Tapuria Sameer Junnarkar Mahmoud Abu-amara Barry Fuller Alexander M Seifalian Brian R Davidson | 2016 | World Journal of Gastroenterology2016，22，33： | 3 |
| 18 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 19 | Cholangiocarcinoma显示文摘 | Shahid A Khan Howard C Thomas Brian R Davidson Simon D Taylor-Robinson | 2005 | The Lancet . 2005 (9493)2005，，： | 3 |
| 20 | Evaluating the quality of feed fats and oils and their effects on pig growth performance显示文摘Feed fats and oils provide significant amounts of energy to swine diets, but there is large variation in composition,quality, feeding value, and price among sources. Common measures of lipid quality include moisture, insolubles,and unsaponifiables(MIU), titer, and free fatty acid content, but provide limited information regarding their feeding value. Lipid peroxidation is an important quality factor related to animal growth performance and health, but maximum tolerable limits in various lipids have not been established. Several indicative assays can be used to detect the presence of various peroxidation compounds, but due to the complexity and numerous compounds produced and degraded during peroxidation process, no single method can adequately determine the extent of peroxidation. Until further information is available, using a combination of peroxide value, thiobarbituric acid reactive substances(TBARS), and anisidine value appear to provide a reasonable assessment of the extent of peroxidation in a lipid at a reasonable cost. However, fatty acid composition of the lipid being evaluated should be considered when selecting specific assays. Predictive tests can also be used to estimate the stability or susceptibility of lipids to peroxidation and include active oxygen method, oil stability index, and oxygen bomb method. A review of 16 published studies with pigs has shown an average decrease of 11.4% in growth rate, 8.8% feed intake fed isocaloric diets containing peroxidized lipids compared to diets containing unperoxidized lipids of the same source.Furthermore, serum vitamin E content was generally reduced and serum TBARS content was increased when peroxidized lipids were fed in these studies, suggesting that feeding peroxidized lipids negatively affects metabolic oxidative status of pigs. However, it is unclear if antioxidants are useful additions to lipids to maintain optimal nutritional value, or if their addition to swine diets is beneficial in overcoming a metabolic oxidative challenge. | Gerald C Shurson Brian J Kerr Andrea R Hanson | 2016 | Journal of Animal Science and Biotechnology2016，7，3： | 3 |
您所在的机构暂未开通此部分的功能，请联系管理员