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| 1 | Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010显示文摘Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic. | Chakshu Sharma Karim M Eltawil Paul D Renfrew Mark J Walsh Michele Molinari | 2011 | World Journal of Gastroenterology2011，17，7： | 28 |
| 2 | Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism显示文摘Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domaincontaining 5(FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue(WAT) and uncoupling protein 1(UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal(IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-k B ligand(RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice. | Jin Zhang Paloma Valverde Xiaofang Zhu Dana Murray Yuwei Wu Liming Yu Hua Jiang Michel M Dard Jin Huang Zhiwei Xu Qisheng Tu Jake Chen | 2017 | Bone Research2017，5，1： | 23 |
| 3 | Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference显示文摘 | Jordi Bruix Morris Sherman Josep M Llovet Michel Beaugrand Riccardo Lencioni Andrew K Burroughs Erik Christensen Luigi Pagliaro Massimo Colombo Juan Rodés | 2001 | Journal of Hepatology2001，，3： | 11 |
| 4 | Rifaximin vs conventional oral therapy for hepatic encephalopathy:A meta-analysis显示文摘AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le. | Karim M Eltawil Marie Laryea Kevork Peltekian Michele Molinari | 2012 | World Journal of Gastroenterology2012，18，8： | 9 |
| 5 | Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity显示文摘Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure. | Sophia Hauck Paula Zager Norbert Halfter Elke Wandel Marta Torregrossa Ainur Kakpenova Sandra Rother Michelle Ordieres Susann Räthel Albrecht Berg Stephanie Möller Matthias Schnabelrauch Jan C.Simon Vera Hintze Sandra Franz | 2021 | Bioactive Materials2021，6，12： | 7 |
| 6 | 大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析显示文摘目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。 | 孟夏 刘聪(校) 陈仁杰 郑湃(译) 阚海东(校) Francesco Sera Ana Vicedo-Cabrera Ai Milojevic Maria Guo Yuming Tong Shilu Micheline de Sousa Zanotti Stagliorio Coelh Paulo Hilario Nascimento Saldiva Eric Lavigne Patricia Matus Correa Nicolas Valdes Ortega Samuel Osorio Garcia Jan Kysely Ales Urban Hans Orru Marek Maasikmets Jouni J K Jaakkola Niilo Ryti Veronika Huber Alexandra Schneider Klea Katsouyanni Antonis Analitis Masahiro Hashizume Yasushi Honda Chris Fook Sheng Ng Baltazar Nunes João Paulo Teixeira Iulian Horia Holobaca Simona Fratianni Ho Kim Aurelio Tobias Carmeníniguez Bertil Forsberg ChristoferÅström Martina S Ragettli Yue-Liang Leon Guo Shih-Chun Pan Shanshan Li Michelle L Bell Antonella Zanobetti Joel Schwartz Tangchun Wu Antonio Gasparrini | 2021 | 英国医学杂志中文版2021，24，8： | 7 |
| 7 | Irritable bowel syndrome: A concise review of current treatment concepts显示文摘Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders causing patients to seek medical treatment. It is relatively resource intensive and the source of significant morbidity. Recent insights into the pathophysiology and treatment of IBS has given clinicians more options than ever to contend with this disorder. The purpose of our paper is to review older, 'classic' treatments for IBS as well as newer agents and 'alternative' therapies. We discuss the evidence base of these drugs and provide context to help develop appropriate treatment plans for IBS patients. | Geoffrey C Wall Ginelle A Bryant Michelle M Bottenberg Erik D Maki rew R Miesner | 2014 | World Journal of Gastroenterology2014，20，27： | 5 |
| 8 | Intestinal pseudo-obstruction caused by herpes zoster:Case report and pathophysiology显示文摘Herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be consideredwhen dealing with non-obstructive(adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery. | Roberto Anaya-Prado José V Pérez-Navarro Ana Corona-Nakamura Michelle M Anaya-Fernández Roberto Anaya-Fernández Marian Eliza Izaguirre-Pérez | 2018 | World Journal of Clinical Cases2018，6，6： | 4 |
| 9 | Control of stem cell fate by engineering their micro and nanoenvironment显示文摘Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix(ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine. | Michelle F Griffin Peter E Butler Alexander M Seifalian Deepak M Kalaskar | 2015 | World Journal of Stem Cells2015，7，1： | 3 |
| 10 | Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review显示文摘Langerhans cell histiocytosis(LCH) is a rare syndrome characterized by unifocal,multifocal unisystem,or disseminated/multi-system disease that commonly involves the bone,skin,lymph nodes,pituitary,or sometimes lung(almost exclusively in smokers) causing a variety of symptoms from rashes and bone lesions to diabetes insipidus or pulmonary infiltrates.We present a previously unreported case of gastrointestinal LCH as well as a novel characteristic lesion affecting the colon of a young woman who presented with signs and symptoms mimicking acute on chronic appendicitis.Immunohistochemical analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100,CD1a,and langerin reactivity.The patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy. | Mohammad M Karimzada Michele N Matthews Samuel W French Daniel De Ugarte Dennis Y Kim | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，3： | 3 |
| 11 | Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery显示文摘AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut inflammation.METHODS: Four week old piglets were randomly allocated to a no-surgery 'control' group(n = 6) or a 'transection surgery' group(n = 5).During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was re-anastomosed.Piglets received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks post-surgery.Clinical outcomes including weight, stool consistency and presence of stool fat globules were monitored.High throughput DNA sequencing of colonic content was used to detect surgery-relateddisturbances in microbial composition at phylum, family and genus level.Diversity and richness estimates were calculated for the control and minor surgery groups.As disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines(TNF, IL1 B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks post-surgery.RESULTS: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes phyla.Family level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae(2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae(0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection surgery.Similarly, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ± 1.08, P < 0.01), Alistipes(4.82 ± 1.73 vs 0.18 ± 0.13, P < 0.05) and Thalassospira(0.53 ± 0.19 vs 0.00 ± 0.00, P < 0.05).Surgeryassociated microbial dysbiosis was accompanied by increased gene expression of markers of inflammation.Within the ileum IL6 expression was decreased(4.46 ± 1.60 vs 0.24 ± 0.06, P < 0.05) following transection surgery.In the terminal ileum, gene expression of TNF was decreased(1.51 ± 0.13 vs 0.80 ± 0.16, P < 0.01) and IL18(1.21 ± 0.18 vs 2.13 ± 0.24, P < 0.01), IL12(1.04 ± 0.16 vs 1.82 ± 0.32, P < 0.05) and IL10(1.04 ± 0.06 vs 1.43 ± 0.09, P < 0.01) gene expression increased following transection surgery.Within the colon, IL12(0.72 ± 0.13 vs 1.78 ± 0.28, P < 0.01) and IL10(0.98 ± 0.02 vs 1.95 ± 0.14, P < 0.01) gene expression were increased following transection surgery.CONCLUSION: This study suggests that minor abdominal surgery in infants, results in long-term alteration of the colonic microbial composition and persistent gastrointestinal inflammation. | Susan Lapthorne Julie E Bines Fiona Fouhy Nicole L Dellios Guineva Wilson Sarah L Thomas Michelle Scurr Catherine Stanton Paul D Cotter Prue M Pereira-Fantini | 2015 | World Journal of Gastroenterology2015，21，14： | 3 |
| 12 | Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy:A case report and review of literature显示文摘BACKGROUND Primary extra-gastrointestinal stromal tumors(E-GIST)of the liver are rare.The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect.Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care.However,under specific circumstances,a cytoreductive approach may represent a therapeutic option.We describe herein the case of an 84-year-old woman who presented with a tender,protruding epigastric mass.Abdominal computed tomography scan revealed a large,heterogeneous mass located across segments III,IV,V,and VIII of the liver.The initial approach was transarterial embolization of the tumor,which elicited no appreciable response.Considering the large size and central location of the tumor and the advanced age of the patient,non-anatomic complete resection was indicated.Due to substantial intraoperative bleeding and hemodynamic instability,only a near-complete resection could be achieved.Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver.Considering the risk/benefit ratio for therapeutic options,debulking surgery may represent a strategy to control pain and prolong survival.CASE SUMMARY Here,we present a case report of a patient diagnosed with E-GIST primary of the liver,which was indicated a cytoreductive surgery and adjuvant therapy with imatinib.CONCLUSION E-GIST primary of the liver is a rare conditional,the treatment is with systemic therapy and total resection surgery.However,a cytoreductive surgery will be necessary when a complete resection is no possible. | Michel Ribeiro Fernandes Caroline Lorenzoni Almeida Ghezzi Tomaz J M Grezzana-Filho Flávia Heinz Feier Ian Leipnitz Aljamir Duarte Chedid Carlos Thadeu Schmidt Cerski Marcio Fernandes Chedid Cléber RositoPinto Kruel | 2021 | World Journal of Gastrointestinal Surgery2021，13，3： | 3 |
| 13 | Endoscopic palliation of malignant biliary stricture显示文摘Malignant biliary strictures often present late after the window for curative resection has elapsed. In such patients, the goal of therapy is typically focused on palliation. While historically, palliative measures were performed surgically, the advent of endoscopic intervention offers minimally invasive options to provide relief of symptoms, improve quality of life, and in some cases, increase survival of these patients. Some of these therapies, such as endoscopic biliary decompression, have become mainstays of treatment for decades, whereas newer modalities, including radiofrequency ablation, and photodynamic therapy offer additional options for patients with incurable biliary malignancies. | Sanjay M Salgado Monica Gaidhane Michel Kahaleh | 2016 | World Journal of Gastrointestinal Oncology2016，8，3： | 3 |
| 14 | Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations显示文摘 | Roland Asmar Annie Rudnichi Jacques Blacher Gérard M London Michel E Safar | 2001 | American Journal of Hypertension2001，，2： | 3 |
| 15 | Pharmacology of adapalene 显示文摘 | Michel S Jomard A Demarchez M | 1998 | Br J Dermatol1998，139，52： | 2 |
| 16 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 17 | Six-minute walking test performance is associated with survival in cirrhotic patients显示文摘BACKGROUND Patients with cirrhosis are at risk of cirrhotic cardiomyopathy,with resulting cardiac dysfunction and exercise limitations.Six minute walking test(6MWT)assesses functional status and predicts morbidity and mortality in cardiopulmonary diseases.AIM To determine if it associates with mortality by analyzing 6MWT performance in patients with liver cirrhosis.METHODS A cohort of 106 cirrhotic patients was evaluated in the outpatient setting with echocardiogram and 6MWT and follow up for one year to document hepatic decompensation and mortality.The distance in meters was recorded at the end of 6 min(6MWD).RESULTS This cohort had a mean age of 51 years and 56%male;patients were staged as Child A in 21.7%,B 66%and C 12.3%.Walk distance inversely correlated with Child scores,and was significantly reduced as Child stages progresses.Patients who died(10.4%)showed shorter mean 6MWD(P=0.006).Low 6MWD was an independent predictor of mortality(P=0.01).CONCLUSION 6MWT is a noninvasive inexpensive test whose result is related to Child scores and mortality.It is useful to identify patients with liver cirrhosis at high risk of mortality for closer monitoring and potential early intervention. | Carolina Frade M G Pimentel Ana Cristina de Castro Amaral Adriano Miziara Gonzalez Michelle Lai Danielde Oliveira Mota Maria Lucia Gomes Ferraz Wilson Mathias Junior Mario Kondo | 2021 | World Journal of Hepatology2021，13，11： | 2 |
| 18 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 19 | TGFβ1 and radiation fibrosis: a master switch and a specific therapeutic target?显示文摘 | Michele M Jean-louse L Sylvie D | 2000 | Int J Radiation Oncol Biol Phys2000，47，2： | 2 |
| 20 | Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection显示文摘Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease severity.In this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory markers.Remarkably,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 infection.Moreover,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were observed.These findings contribute to a better understanding of the immunological sequelae of COVID-19. | Alberto Pérez-Gómez Joana Vitallé Carmen Gasca-Capote Alicia Gutierrez-Valencia María Trujillo-Rodriguez Ana Serna-Gallego Esperanza Muñoz-Muela María de los Reyes Jiménez-Leon Mohamed Rafii-El-Idrissi Benhnia Inmaculada Rivas-Jeremias Cesar Sotomayor Cristina Roca-Oporto Nuria Espinosa Carmen Infante-Domínguez Juan Carlos Crespo-Rivas Alberto Fernández-Villar Alexandre Pérez-González Luis Fernando López-Cortés Eva Poveda Ezequiel Ruiz-Mateos JoséMiguel Cisneros Sonsoles Salto-Alejandre Judith Berastegui-Cabrera Pedro Camacho-Martínez Carmen Infante-Domínguez Marta Carretero-Ledesma Juan Carlos Crespo-Rivas Eduardo Márquez JoséManuel Lomas Claudio Bueno Rosario Amaya JoséAntonio Lepe Jerónimo Pachón Elisa Cordero Javier Sánchez-Céspedes Manuela Aguilar-Guisado Almudena Aguilera Clara Aguilera Teresa Aldabo-Pallas Verónica Alfaro-Lara Cristina Amodeo Javier Ampuero María Dolores Avilés Maribel Asensio Bosco Barón-Franco Lydia Barrera-Pulido Rafael Bellido-Alba Máximo Bernabeu-Wittel Candela Caballero-Eraso Macarena Cabrera Enrique Calderón Jesús Carbajal-Guerrero Manuela Cid-Cumplido Yael Corcia-Palomo Juan Delgado Antonio Domínguez-Petit Alejandro Deniz Reginal Dusseck-Brutus Ana Escoresca-Ortega Fátima Espinosa Nuria Espinosa Michelle Espinoza Carmen Ferrándiz-Millón Marta Ferrer Teresa Ferrer Ignacio Gallego-Texeira Rosa Gámez-Mancera Emilio García Horacio García-Delgado Manuel García-Gutiérrez María Luisa Gascón-Castillo Aurora González-Estrada Demetrio González Carmen Gómez-González Rocío González-León Carmen Grande-Cabrerizo Sonia Gutiérrez Carlos Hernández-Quiles Inmaculada Concepción Herrera-Melero Marta Herrero-Romero Luis Jara Carlos Jiménez-Juan Silvia Jiménez-Jorge Mercedes Jiménez-Sánchez Julia Lanseros-Tenllado Carmina López Isabel López Álvaro López-Barrios Luis F.López-Cortés Rafael Luque-Márquez Daniel Macías-García Guillermo Martín-Gutiérrez Luis Martín-Villén JoséMolina Aurora Morillo María Dolores Navarro-Amuedo Dolores Nieto-Martín Francisco Ortega María Paniagua-García Amelia Peña-Rodríguez Esther Pérez Manuel Poyato Julia Praena-Segovia Rafaela Ríos Cristina Roca-Oporto Jesús F.Rodríguez María Jesús Rodríguez-Hernández Santiago Rodríguez-Suárez Ángel Rodríguez-Villodres Nieves Romero-Rodríguez Ricardo Ruiz Zida Ruiz de Azua Celia Salamanca Sonia Sánchez Víctor Manuel Sánchez-Montagut César Sotomayor Alejandro Suárez Benjumea Javier Toral | 2021 | Cellular & Molecular Immunology2021，18，9： | 2 |
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