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Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α

World Journal of Gastroenterology 2015年第4期21卷 1108-1116页

作者： Andrea Ferrigno laura giuseppina di pasqua Alberto Bianchi Plinio Richelmi Mariapia VairettiAndrea Ferrigno Unit of Cellular and Molecular Pharmacology and Toxicology Department of Interna Medicine and TherapeuticsUniversity of PaviaPavia 27100 Italy

AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 ℃. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; p H of the perfusate was also evaluated; Hi F-1α m RNA and protein expression were analyzed by real time-polymerase chain reaction and ELi SA, respectively. RESULTS: Livers perfused at 10 and 20 ℃ showed no difference in lactate dehydrogenase release after 6 h of perfusion(0.96 ± 0.23 vs 0.93 ± 0.09 m U/min per g) and had lower hepatic damage as compared to 30 and 37 ℃(5.63 ± 0.76 vs 527.69 ± 45.27 m U/min per g, respectively, P s < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃than in livers perfused at 30 and 37 ℃(0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, P s < 0.01). No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃(121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/m L, respectively, P s < 0.02), and low relative Hi F-1α m RNA(0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, P s < 0.05) and protein(3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s < 0.05) ***: Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃.

关键词： Anaerobiosis Hypoxia inducible factor-1 α ischemia

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Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract

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World Journal of Gastroenterology 2017年第25期23卷 4500-4507页

作者： Andrea Ferrigno Clarissa Berardo laura G di pasqua Veronica Siciliano Plinio Richelmi Mariapia Vairetti Department of Internal Medicine and Therapeutics (Cellular and Molecular Pharmacology and Toxicology) University of Pavia

Metabotropic glutamate receptor subtype 5 (mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other mGluR subtypes, mGluR5s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system (CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal (GI) tract and accessory digestive organs such as the tongue, liver and pancreas. Following identification of mGluR5s in the mouth, various studies have subsequently demonstrated its involvement in mechanical allodynia, inflammation, pain and oral cancer. mGluR5 expression has also been identified in gastroesophageal vagal pathways. Indeed, experimental and human studies have demonstrated that mGluR5 blockade reduces transient lower sphincter relaxation and reflux episodes. In the intestine, mGluR5s have been shown to be involved in the control of intestinal inﬂammation, visceral pain and the epithelial barrier function. In the liver, mGluR5s have a permissive role in the onset of ischemic injury in rat and mice hepatocytes. Conversely, livers from mice treated with selective negative allosteric modulators and mGluR5 knockout mice are protected against ischemic injury. Similar results have been observed in experimental models of free-radical injury and in vivo mouse models of acetaminophen intoxication. Finally, mGluR5s in the pancreas are associated with insulin secretion control. The picture is, however, far from complete as the review attempts to establish in particular as regards identifying specific targets and innovative therapeutic approaches for the treatment of GI disorders.

关键词： Metabotropic glutamate receptor subtype 5 Esophagus Intestine Liver Pancreas

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Liver plays a central role in asymmetric dimethylargininemediated organ injury

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World Journal of Gastroenterology 2015年第17期21卷 5131-5137页

作者： Andrea Ferrigno laura G di pasqua Clarissa Berardo Plinio Richelmi Mariapia Vairetti Department of Internal Medicine and Therapeutics University of Pavia27100 PaviaItaly

Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;*** is synthesized by protein methyltransferases followed by proteolytic *** is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the *** liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver *** mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to *** plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.

关键词： Liver Asymmetric dimethylarginine Nitricoxide Nitric oxide-synthase Multiple organ failure

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Control of embryonic stem cell metastability by L-proline catabolism

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分子细胞生物学报:英文版 2011年第2期3卷 108-122页

作者： laura Casalino Stefania Comes giuseppina Lambazzi Benedetta De Stefano Stefania Filosa Sandro De Falco Dario De Cesare Gabriella Minchiotti Eduardo Jorge Patriarca Stem Cell Fate Laboratory Institute of Genetics and Biophysics“A.Buzzati-Traverso”CNRNaplesItaly

The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,*** capacity to fluctuate between different states of pluripotency,are not fully *** developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(*** and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC *** compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent *** EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to ***,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,***,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,*** together,our data provide evidence that ESC metastability can be regulated at a metabolic level.

关键词： embryonic stem cells L-proline vitamin C colony phenotype pluripotent states metastability

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Neurodegenerative diseases as proteinopathies-driven immune disorders

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Neural Regeneration Research 2020年第5期15卷 850-856页

作者： Fausta Ciccocioppo giuseppina Bologna Eva Ercolino laura Pierdomenico pasquale Simeone Paola Lanuti Damiana Pieragostino Piero Del Boccio Marco Marchisio Sebastiano Miscia Department of Medicine and Aging Science University “G. d’Annunzio” of Chieti-PescaraChietiItaly Centre on Aging Sciences and Translational Medicine (Ce.S.I-MeT) University “G. d’Annunzio” of Chieti-PescaraChietiItaly Department of Medical Oral and Biotechnological SciencesUniversity “G. d’Annunzio” of Chieti-PescaraChietiItaly

In the pathophysiology of neurodegenerative disorders,the role of misfolded protein deposition leading to neurodegeneration has been primarily *** the last decade,however,it has been proposed a parallel involvement of innate immune activation,chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by *** insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative ***,the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative ***,we have reviewed the pathogenic hypothesis in neurodegenerative pathologies,underling the links between the deposition of misfolded protein mechanisms and the immune activation.

关键词： adaptive immunity choroid plexus immunotherapy innate immunity neurodegenerative diseases neuroinflammation proteinopathies

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The Influence of different Nitrogen Treatments on the Growth and Yield of Basil （Ocimum Basificum L.）

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Journal of Chemistry and Chemical Engineering 2011年第9期5卷 799-803页

作者： laura Frabboni giuseppina de Simone Vittoria Russo Department of Agro-Environmental Sciences Chemistry and Plant Protection Univ. Foggia Italy

Sweet basil （Ocimum basilicum L.） is a popular culinary herbal crop grown for the fresh or dry leaf, essential oil and seed markets. Recently, basil has been shown to rank highest among spices and herbal crops for xanthophyll carotenoids, which are associated with a decreased risk of cancer and age-related eye diseases. Nitrogen fertilizer encourages vegetative growth and increases oil yield in aromatic plants by enhancing leaf area development and photosynthetic rate. Our goal was to determine the influence of different concentrations of nitrogen （N） fertilization on basil physiology. The trial examined the cultivation of Ocimum basilicum L. （variety Genovese gigante）. The experiment was carried out under Mediterranean climatic conditions. The experiment considered the adoption of three nitrogen （N） treatments （0, 160, 240 kg N ha-1）. The following biometric parameters were determined： plant height, leaves per plant, leaf to stem ratio, number of branchings per plant, leaf area index （LAI）, above-ground fresh and leaf biomass. Considering the parameters most strictly linked to the economic results （total fresh weight, fresh weight of the leaves and total dry weight）, we found that 160 kg N ha^-1 treatment showed the best performance.

关键词： Nitrogen treatment basil yield yield components growth Ocimum basilicum L.

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Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

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World Journal of Hepatology 2016年第19期8卷 815-824页

作者： Alessio Strazzulla Giuseppe Coppolino Concetta di Fatta Francesca Giancotti giuseppina D'Onofrio Maria Concetta Postorino Maria Mazzitelli Selma Valerie Mammone Innocenza Gentile laura Rivoli Eleonora Palella Tiziana Gravina Chiara Costa Vincenzo Pisani Vincenzo De Maria Giorgio Settimo Barreca Nadia Marascio Alfredo Focà Giorgio Fuiano Elio Gulletta Carlo Torti Infectious diseases Unit Department of Medical and Surgical Sciences "Magna Graecia" University Nephrology and dialysis Unit "Pugliese-Ciaccio" Hospital Clinical Pathology Unit Department of Health Sciences "Magna Graecia" University Hepatology Unit "Mater Domini" Teaching Hospital Nephrology Unit Department of Medical and Surgical Sciences "Magna Graecia" University Microbiology Unit Department of Health Sciences "Magna Graecia" University

AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

关键词： directly acting antivirals Hepatitis C virus Inflammation Neutrophil gelatinase lipocalin Tubular impairment

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Aggressive therapy with statins in elderly and malnourished patients with acute myocardial infarction： is the right time to change？

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Journal of Geriatric Cardiology 2016年第10期13卷 815-816页

作者： Annamaria Mazzone Umberto Paradossi Sergio Berti giuseppina Basta Fondazione G. Monasterio CNR Regione Toscana Pisa Massa Italy CNR Institute of Clinical Physiology Via G. Moruzzi Pisa Italy

The changes in the demographic profile of the population with longer life expectancy are mainly due to an improvement of lifestyle, prevention and care of chronic diseases, such as cardiovascular disease.

关键词： Acute myocardial infarction Elderly Malnutrition Statin

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The Neurologist in the Emergency Room: Prospective Study of the Neurological Emergency Group in Lombardia

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Journal of Health Science 2019年第4期7卷 254-261页

作者： MariaLuisa Delodovici Marco Mauri Megi Meneri Marco Gallazzi Elena Ballabio giuseppina Borutti Maria Vittoria Calloni Elisa Candeloro Bruno Censori Claudio De Piazza laura Fusi Franca Mazzucchelli Ignazio Santilli Elisabetta Forapani Chiara Scaccabarozzi Maria Sessa Lucia Tancredi Massimiliano Braga Dept. of Neurology and Stroke Unit Ospedale di Circolo e Fondazione MacchiUniversità dell’InsubriaASST-Settelaghile Luigi Borri 57 21100 VareseItaly Dept. of Neurology Ospedale di Desio (MB) director G. Mazzini 1 20832 Desio (MB)Italy Dept. of Neurology ASST Lecco-Ospedale A. Manzonidell’Eremo 9/11 23900 LeccoItaly Dept. of Neurology Ospedale di Cremona ASST Cremona Directorle Concordia 1 26100 CremonaItaly Dept. of Neurology Ospedale Sant’Anna ComoRavona 20 22042 SFermo della BattagliaComoItaly Dept. of Neurology Ospedale di Vimercate (MB) Santi Cosma e Damiano 10 20871 Vimercate (MB)Italy Dept. of Neurology Ospedale S. Carlo BorromeoA. Mosca 12 20152 MilanoItaly Dept. of Neurology Director Ospedale Civile di VogheraVolturno 14 Voghera 27058 (PV)Italy Dept. of Neurology Ospedale di Legnano ASST Ovest MilanesePapa Giovanni Paolo II20025 Legnano (MI)Italy Dept. of Neurology Fondazione IRCCS C. Mondino Mondino 2Pavia 27100Italy Dept. of Neurology ASST Papa Giovanni XXIII Piazza OMS 1 24127 BergamoItaly Dept. of Neurology Ospedale Valduce ComoDante Alighieri 11 22100 ComoItaly Dept. of Neurology Ospedale di Saronno ASST Valle olonaPiazzale Borella 1 Saronno 21047 (VA)Italy Dept. of Neurology Ospedale S. Antonio Abate Gallarate. Pastori 4 21013 Gallarate VareseItaly

Purpose of the work was to quantify the workloads and the neurologist’s commitment in ER, to verify the management of urgencies and appropriateness of neurological counseling requests. Neurologic emergencies are frequent in elderly patients and are associated with high morbidity and mortality. Due to the aging population, neurologic pathologies in emergency room (ER) are widely expected to increase. The role of the neurologist in this context is controversial. Methods: in 14 operative units of neurology a prospective collection of neurological evaluations in ER was carried out using boards of detection of the most frequent neurological clinical pictures seen in the course of a week. Data were collected from 738 cases. Attention was focused on cerebrovascular diseases (CVD), impairment of consciousness, epilepsy, headache, dizziness, head trauma and disorders of the peripheral nervous system (PNS). Achievements: neurological consultations were on average 5% of total accesses to ER. The most common pathology seen was ischemic stroke. After counseling most patients were discharged home. The CVD required the greatest commitment to the specialist. The usefulness of the specialized neurological “filter” has been confirmed in a non-simple operative context, aimed at optimizing the appropriateness of the hospitalization and the economy of the diagnostic path.

关键词： Emergency room neurological diseases neurology workload

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小胶质细胞在光/暗周期过程中调节海马突触传递和睡眠持续时间

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神经损伤与功能重建 2022年第5期17卷 310-310页

作者：杜一星(编译) Department of Physiology and Pharmacology Sapienza University of Rome Axe Neurosciences Centre de Recherche du CHU de Québec Université Laval Quebec City Department of Neurology San Raffaele of Cassino 4. National Research Council Institute of Biochemistry and Cell Biology (EMMA/Infrafrontier/IMPC ) International Campus "A. Buzzati-Traverso" INRAE Bordeaux INP NutriNeuro UMR 1286 Bordeaux University Tecniplast S.P.A. Buguggiate Department of Molecular Medicine Sapienza University INSERM Neurocentre Magendie Physiopathologie de la Plasticité Neuronale division of Medical Sciences University of Victoria The Department of Biochemistry and Molecular Biology The University of British Columbia Department of Physiology and Pharmacology Sapienza University Laboratory affiliated to Istituto Pasteur Italia Department of Neurophysiology Neuropharmacology Inflammaging IRCCS Neuromed

小胶质细胞是大脑的常驻巨噬细胞,通过感知神经元活动并支持突触重塑和可塑性积极促进脑实质的稳态。虽然已有研究表明星形胶质细胞在睡眠中的不同作用,但小胶质细胞在调节睡眠/觉醒周期和白天不同阶段调节突触活动中的作用尚未深入研... 详细信息

小胶质细胞是大脑的常驻巨噬细胞,通过感知神经元活动并支持突触重塑和可塑性积极促进脑实质的稳态。虽然已有研究表明星形胶质细胞在睡眠中的不同作用,但小胶质细胞在调节睡眠/觉醒周期和白天不同阶段调节突触活动中的作用尚未深入研究。以光作为授时提示,我们研究了用集落刺激因子-1受体拮抗剂PLX5622消除小胶质细胞对雄性小鼠睡眠/觉醒周期和海马突触传递的影响。我们的数据表明,小胶质细胞几乎完全的耗竭会增加NREM睡眠的持续时间并减少海马兴奋性神经传递。由于cx3cr1GFP/GFP小鼠显现与PLX5622处理的小鼠中发现的相同情况,趋化因子fractalkine受体CX3CR1在这些效应中起相关作用。此外,在光照阶段小胶质细胞表达较低水平的cx3cr1;当培养的小胶质细胞受到ATP(一种在睡眠期间释放的嘌呤能分子)的刺激时其cx3cr1表达降低。我们的研究结果表明,小胶质细胞参与调节睡眠,调整其cx3cr1表达以响应光/暗阶段,并以时相依赖性方式调节突触活动。

关键词： cx3cr1 脑电图长期增强小胶质细胞耗竭微型兴奋性突触后电流睡觉眠自发兴奋性突触后电流

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