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1An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure显示文摘Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.María Jesús Tuón Marcelino Alvarez Jesús M Culebras Javier González-Gallego 2009World Journal of Gastroenterology2009,15,25:29
2Risk factors associated with the development of ischemic colitis显示文摘AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003.IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible his-tology.Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of colitis.Cases were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was performed.RESULTS:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%women.The principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(P<0.001);diabetes mellitus(P =0.025);peripheral arterial disease(P=0.004);heart failure(P=0.026);treatment with hypotensive drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(P<0.001).Finally,the following variables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associated with diabetes,dyslipid-emia,presence of heart failure,peripheral arterial dis-ease and treatment with digoxin or ASA.Joaquín Cubiella Fernández Luisa Núez Calvo Elvira González Vázquez Maria Jesús García García Maria Teresa Alves Pérez Isabel Martínez Silva Javier Fernández Seara 2010World Journal of Gastroenterology2010,16,36:27
3Alcoholic liver disease:Utility of animal models显示文摘Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero 2018World Journal of Gastroenterology2018,24,45:26
4冠状动脉内影像学临床应用专家共识(第一部分):对冠状动脉介入治疗的指导与优化显示文摘欧洲心血管介入协会(EAPCI)专家组系统总结了血管内超声(IVUS)和光学相干断层成像(OCT)这两种血管内影像学检查临床应用指征的现有证据,提供了关于IVUS和OCT指导经皮冠状动脉介入治疗(PCI)的应用价值,并明确了最可能从腔内影像学指导的介入治疗中获得临床收益的患者或病变类型,同时详细论述了PCI前如何使用IVUS或OCT优化支架尺寸(支架长度和直径)和手术策略的选择。此外,专家推荐对支架失败(支架内再狭窄或支架内血栓形成)的患者应常规进行冠状动脉内影像学检查,并首选OCT。最后,重点论述了IVUS和OCT在指导PCI和评估支架失败两个方面的优势和局限性,并对未来需要深入研究的领域进行了展望。Lorenz Raber Gary S Mintz Konstantinos C Koskinas Thomas W Johnson Niels R Holm Yoshinubo Onuma Maria D Radu Michael Joner Bo Yu Haibo Jia Nicolas Meneveau Jose M.de la Torre Hemandez Javier Escaned Jonathan Hill Francesco Prati Antonio Colombo Carlo di Mario Evelyn Regar Davide Capodanno William Wijns Robert A Byme Giulio Guagliumi 2019中华心血管病杂志2019,47,1:17
5Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TENOSIMP-B study显示文摘AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with LAM.METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed.RESULTS Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA(HBV-DNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.Manuel Rodríguez Juan Manuel Pascasio Enrique Fraga Javier Fuentes Martín Prieto Gloria Sánchez-Antolín Jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet Jose Antonio Pons Jose Manuel González Miguel Angel Casado Francisco Jorquera 2017World Journal of Gastroenterology2017,23,41:16
6IL28B polymorphisms associated with therapy response in Chilean chronic hepatitis C patients显示文摘AIM:To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus CV.METHODS:We studied two groups of patients with chronic CV infection genotype 1,under standard combined treatment with pegylated interferon plus ribavirin.One group consisted of 50 patients with sustained virological response,whereas the second group consisted of 49 null responders.In order to analyze the IL28B single nucleotide polymorphisms rs12979860,rs12980275 and rs8099917,samples were used for polymerase chain reaction amplification,and the genotyping was performed by restriction fragment lengthpolymorphism.RESULTS:The IL28B rs12979860 CC,rs12980275 AA and rs8099917 TT genotypes were much more frequently found in patients with sustained virological response compared to null responders 38%,44% and 50% vs 2%,8.2% and 8.2%,respectively.These differences were highly significant in all three cases(P < 0.0001.CONCLUSION:The three IL28B polymorphisms studied are strongly associated with sustained virological response to therapy in Chilean patients with chronic CV genotype 1.Mauricio Venegas Rodrigo A Villanueva Katherine González Javier Brahm 2011World Journal of Gastroenterology2011,17,31:13
7Pathogenesis of occult chronic hepatitis B virus infection显示文摘Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this'occult'HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.Rocio Aller de la Fuente María L Gutiérrez Javier Garcia-Samaniego Conrado Fernández-Rodriguez Jose Luis Lledó Gregorio Castellano 2011World Journal of Gastroenterology2011,17,12:12
8Efficacy of neoadjuvant therapy and surgical rescue for locally advanced hepatoblastomas:10 year single-center experience and literature review显示文摘AIM:To report our experience with long-term outcomes after multimodal management therapy.METHODS:An observational retrospective study was performed containing seven patients with hepatoblastoma(Hbl)treated in our institution,a tertiary referral center,from 2003 to 2011.Demographic,preoperative,surgical,and outcome variables were collected.A survival analysis and a review of the current literature related to combination neoadjuvant chemotherapy and surgical resection on Hbl were performed.RESULTS:The median age at surgery was 14.4 mo,with a male to female ratio of 4:3.Pretext staging at diagnosis was as follows:stageⅠ,4 cases;stageⅡ,2 patients;and stageⅢ,1 case.Mean pretreatment tumor volume was 735 cm3.Five out of seven patients received neoadjuvant chemotherapy according to SIOPEL-3 or SIOPEL-6 protocols.Tumor volume and alphafetoprotein levels significantly dropped after neoadjuvant therapy.Surgical procedures performed included hemihepatectomies,segmentectomies and atypical resection.All patients received chemotherapy after surgery.Median postoperative hospital stay was 8 d.All patients were alive and disease-free after a median follow-up period of 23 mo.With regards to the literature review,seventeen articles were found that were related to our search.CONCLUSION:Our series shows how multimodal management of Hbl,exhaustive control and a meticulous surgical approach leads to almost 100%complete resection with optimal postoperative results.Dolores Ayllon Teran Oscar Gómez Beltran Rubén Ciria Bru Elena Mateos González María José Pea Rosa Antonio Luque Molina Pedro López Cillero Javier Briceo Delgado 2014World Journal of Gastroenterology2014,20,29:12
9Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests显示文摘AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow(BF) was analyzed by arterial spin labeling(ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy(MHE). Images were collected using a 3 Tesla MR scanner(Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score(PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins(IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated.RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere(P = 0.03) and vermis(P = 0.012) and reduced in occipital lobe(P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE(P = 0.02). Bimanual coordination was impaired in patients without MHE(P = 0.05) and much more in patients with MHE(P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE(P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE(P< 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A(NCT-A), B(NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide(NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe.CONCLUSION: Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum.Vicente Felipo Amparo Urios Carla Giménez-Garzó Omar Cauli Maria-Jesús Andrés-Costa Olga González Miguel A Serra Javier Sánchez-González Roberto Aliaga Remedios Giner-Durán Vicente Belloch Carmina Montoliu 2014World Journal of Gastroenterology2014,20,33:12
10Role of melatonin on diabetes-related metabolic disorders显示文摘Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.Javier Espino José A Pariente Ana B Rodríguez 2011World Journal of Diabetes2011,2,6:11
11Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications显示文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.Javier A García-Vilas Miguelángel Medina 2018World Journal of Gastroenterology2018,24,33:10
12Isolated intestinal neurofibromatous proliferations in the absence of associated systemic syndromes显示文摘Gastrointestinal tract involvement by neurofi bromatous lesions is rare and occurs most frequently as one of the systemic manifestations of generalized neurofibromatosis type 1 (NF1). In this setting, the lesions may manifest as focal scattered neurofi bromas or as an extensive diffuse neural hyperplasia designated ganglioneuromatosis. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. Rarely, cases of isolated neurofi bromatosis of the large bowel with no prior or subsequent evidence of generalized neurofi bromatosis have been documented. We present the case of a 52 year-old female with abdominal pain and alternating bowel habits. Colonoscopic evaluation revealed multiple small polyps in the cecum and the presence of nodular mucosa in the colon and rectum. Pathologic evaluation of the biopsies from the cecum, descending colon, sigmoid colon, and rectum revealed tangled fascicles of spindle cells expanding the lamina propia leading to separation of the intestinal crypts. Immunohistochemical stains helped confirm the diagnosis of diffuse intestinal neurofibromatosis. A thorough clinical evaluation failed to reveal any stigmata of generalized neurofibromatosis. This case represents a rare presentation of isolated intestinal neurofi bromatosis in a patient without classic systemic manifestations of generalized neurofibromatosis and highlights the need in such cases for close clinical follow-up to exclude neurofibromatosis type Ⅰ or multiple endocrine neoplasia type Ⅱ.J Elliot Carter Javier A Laurini 2008World Journal of Gastroenterology2008,14,42:9
13Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver显示文摘Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.María Rojas-Feria Manuel Castro Emilio Suárez Javier Ampuero Manuel Romero-Gómez 2013World Journal of Gastroenterology2013,19,42:9
14Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease显示文摘Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate recommendations.Prevention of errors needs knowledge to avoid making such errors through ignorance.However,the amount of knowledge is increasing so quickly that one new danger is an overabundance of information.IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems.With regard to the use of 5-aminosalicylates,the best practice may to be consider abandoning the use of these drugs in patients withsmall bowel Crohn's disease.The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis;once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy.With regard to thiopurines,they seem to be as effective in ulcerative colitis as in Crohn's disease.Underdosing of thiopurines is a form of undertreatment.Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse.Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine.Finally,thiopurine methyltransferase(TPMT)screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.Javier P Gisbert María Chaparro Fernando Gomollón 2011World Journal of Gastroenterology2011,17,30:8
15Umbilical cord as a mesenchymal stem cell source for treating joint pathologies显示文摘Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of life.Regrettably,the regeneration of articular cartilage is a continuing challenge for biomedical research.One of the most promising therapeutic approaches is cellbased tissue engineering,which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured site.The use of healthy chondrocytes has been found to have limitations.A promising alternative cell population is mesenchymal stem cells(MSCs),known to possess excellent proliferation potential and proven capability for differentiation into chondrocytes.The“immunosuppressive”property of human MSCs makes them an important candidate for allogeneic cell therapy.The use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting procedures.An allogeneic cell-based approach would enable MSCs to be isolated from any donor,expanded and cryopreserved in allogeneic MSC banks,providing a readily available source of progenitors for cell replacement therapy.These possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology communities.Our objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.María Carmen Arufe Alexandre De la Fuente Isaac Fuentes Francisco Javier De Toro Francisco Javier Blanco 2011World Journal of Orthopedics2011,2,6:7
16Peritoneal metastases of colorectal origin treated by cytoreduction and HIPEC: An overview显示文摘Colorectal peritoneal carcinomatosis was considered a terminal condition with a merely palliative treatment that included only supportive care, palliative surgery and the best systemic chemotherapy. Since the birth of a new approach, cytoreductive surgery with peritonectomy procedures together with hyperthermic intraperitoneal chemotherapy and/or early postoperative intraperitoneal chemotherapy to treat peritoneal carcinomatosis, many research groups contributed with promising results using this procedure being up to date this strategy the only one that has shown curative benefits on colorectal peritoneal carcinomatosis achieving reported overall survival rates up to 64 mo and fiveyear survival rates up to 51%. The aim of this paper is to expose an updated overview of the therapeutic possibilities of these procedures in colorectal peritoneal metastases in the same way that our Unit of Oncologic Surgery has performed since 1997 with more than four hundred procedures.Alvaro Arjona-Sánchez Francisco Javier Medina-Fernández Francisco Cristobal Mu?oz-Casares Angela Casado-Adam Juan Manuel Sánchez-Hidalgo Sebastián Rufián-Pe?a 2014World Journal of Gastrointestinal Oncology2014,6,10:7
17SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation显示文摘Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.Xavier Palomer MSilvia Román-Azcona Javier Pizarro-Delgado Ana Planavila Francesc Villarroya Brenda Valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera 2020Signal Transduction and Targeted Therapy2020,5,1:7
18满足新版IEC1000-3-2标准规定(2000版)的单相LC滤波整流器的设计显示文摘本文对用于满足新版IEC10 0 0 3 2 (第二版 )电流谐波限制标准规定的单相全桥LC滤波整流器进行了分析和设计。结果表明 ,如果设计适当的滤波电感值 ,本文所述的无源功率因数校正方法可以满足标准所要求的规定。本文分析了新版IEC10 0 0 3 2标准中划分为A类和D类电力电子产品满足标准规定的条件情况。计算机仿真和实验验证理论分析和计算结果。林维明 Javier Sebastián A Fernandez 2002电工电能新技术2002,21,2:7
19Gene expression changes in spleens of the wildlife reservoir species,Eurasian wild boar(Sus scrofa),naturally infected with Brucella suis biovar 2显示文摘Brucella suis is responsible for swine brucellosis worldwide.Of the five different B.suis biovars(bv.),bv.2 appears restricted to Europe where it is frequently isolated from wild boar and hares,can infect pigs and can cause human brucellosis.In this study,the differential gene expression profile was characterized in spleens of Eurasian wild boar naturally infected with B.suis bv.2.Of the 20,201 genes analyzed in the microarray,633 and 1,373 were significantly(fold change > 1.8;P < 0.01) upregulated and downregulated,respectively,in infected wild boar.The analysis was focused on genes that were over represented after conditional test for biological process gene ontology.Upregulated genes suggested that B.suis bv.2 infection induced cell maturation,migration and/or proliferation in infected animals.The genes downregulated in infected wild boar impaired the activity of several important cellular metabolic pathways such as metabolism,cytoskeleton organization and biogenesis,immune response and lysosomal function and vesicle-mediated transport.In addition,the response to stress,sperm fertility,muscle development and apoptosis seemed to be also impaired in infected animals.These results suggested that B.suis bv.2 may use strategies similar to other smooth brucellae to facilitate intracellular multiplication and the development of chronic infections.To our knowledge,this is the first report of the analysis of gene expression profile in hosts infected with B.suis bv.2,which is important to understand the molecular mechanisms at the host-pathogen interface in the main reservoir species with possible implications in the zoonotic cycle of the pathogen.Ruth C.Galindo Pilar M.Muoz María J.de Miguel Clara M.Marin Javier Labairu Miguel Revilla José M.Blasco Christian Gortazar José de la Fuente 2010Journal of Genetics and Genomics2010,37,11:6
20Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding显示文摘AIM To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers(NSBBs) and acute nonresponders received carvedilol.METHODS Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional NSBB(i.e. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.RESULTS Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation(NSBB: 0%, 13.7%, 26.1% vs carvedilol: 0%, 20%, 20%, P = 0.968) or further decompensation(21.2%, 26.1%, 40.9% vs 21.2%, 50.0%, 50.0%, P = 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation [hazard ratio(95% confidence interval): 8.03(2.76-23.37)]. Mortality rates were similar in acute responders and acute nonresponders with compensated(P = 0.428) or decompensated cirrhosis(P = 0.429). No clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional NSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated(r = 0.59, P = 0.001). Up to 69.2% of acute nonresponders gained chronic response with carvedilol.CONCLUSION Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects for reducing portal pressure.José Ignacio Fortea ángela Puente Patricia Ruiz Iranzu Ezcurra Javier Vaquero Antonio Cuadrado María Teresa Arias-Loste Joaquín Cabezas Susana Llerena Paula Iruzubieta Carlos Rodríguez-Lope Patricia Huelin Fernando Casafont Emilio Fábrega Javier Crespo 2018World Journal of Clinical Cases2018,6,13:6
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