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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Neural Regeneration research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Liver disease and COVID-19:The link with oxidative stress,antioxidants and nutrition

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World Journal of Gastroenterology 2021年第34期27卷 5682-5699页

作者： Danijela Ristic-Medic Snjezana Petrovic Aleksandra Arsic Vesna Vucic Group for nutritional Biochemistry and Dietology Centre of Research Excellence in Nutrition and MetabolismNational Institute for Medical ResearchUniversity of BelgradeBelgrade 11129Serbia

Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2).In general,oxidative stress is actively involved in initiation and progression of liver *** liver metabolizes various compounds that produce free *** the oxidative/antioxidative balance is important in coronavirus disease 2019(COVID-19)*** vitamins,essential trace elements and food compounds,such as polyphenols,appear to be promising agents,with effects in oxidative *** of these nutrients suppresses immune function and increases susceptibility to *** micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary *** supplements(β-carotene,vitamin A,vitamin C,vitamin E,and selenium)could have a potential role in patients with liver *** evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of *** trials based on the associations of diet and SARS-CoV-2 infection are ***,it is not possible to definitively determine the dose,route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still *** then,hopefully,this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.

关键词： SARS-CoV-2 COVID-19 Liver injury Antioxidants Nutrients Treatment

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Modulation of individual components of gastric motor response to duodenal glucose

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World Journal of Gastroenterology 2013年第35期19卷 5863-5869页

作者： Adam M Deane Laura K Besanko Carly M Burgstad Marianne J Chapman Michael Horowitz Robert JL Fraser Discipline of Acute Care Medicine University of Adelaide Intensive Care Unit Royal Adelaide Hospital National Health and Medical research Council of Australia centre for clinical research excellence in nutritional physiology and Outcomes Investigation and Procedures Unit Repatriation General Hospital Department of Gastroenterology and Hepatology Royal Adelaide Hospital Discipline of Medicine University of Adelaide Royal Adelaide Hospital

AIM:To evaluate individual components of the antro-pyloro-duodenal(APD)motor response to graded small intestinal glucose infusions in healthy ***:APD manometry was performed in 15healthy subjects(12 male;40±5 years,body mass index 26.5±1.6 kg/m2)during four 20-min intraduodenal infusions of glucose at 0,0.5,1.0 and 1.5 kcal/min,in a randomised double-blinded *** solutions were infused at a rate of 1 mL/min and separated by 40-min"wash-out"*** are mean±*** analyses are repeated measure analysis of variance with Bonferroni post-hoc ***:At 0 kcal/min frequency of pressure waves were:antrum(7.5±1.8 waves/20 min)and isolated pyloric pressure waves(IPPWs)(8.0±2.3 waves/20min)with pyloric tone(0.0±0.9 mmHg).Intraduodenal glucose infusion acutely increased IPPW frequency(P<0.001)and pyloric tone(P=0.015),and decreased antral wave frequency(P=0.007)in a dosedependent fashion.A threshold for stimulation was observed at 1.0 kcal/min for pyloric phasic pressure waves(P=0.002)and 1.5 kcal/min for pyloric tone and antral ***:There is hierarchy for the activation of gastrointestinal motor responses to duodenal glucose *** increase in IPPWs is the first response observed.

关键词： Glucose Gastrointestinal motility Pyloric Antral Duodenum Manometry Motor activity Blood glucose

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Inter-relationships between gastric emptying and glycaemia:Implications for clinical practice

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World Journal of Diabetes 2023年第5期14卷 447-459页

作者： Tejaswini Arunachala Murthy Marianne Chapman Karen L Jones Michael Horowitz Chinmay S Marathe Adelaide Medical School University of AdelaideAdelaide 5000SAAustralia Intensive Care Unit Royal Adelaide HospitalAdelaide 5000SAAustralia NHMRC centre of clinical research excellence in nutritional physiology Interventions and OutcomesUniversity of AdelaideAdelaide 5000SAAustralia Endocrine and Metabolic Unit Royal Adelaide HospitalAdelaide 5000SAAustralia

Gastric emptying(GE)exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes;the rise in blood glucose following oral carbohydrate is greater when GE is relatively more rapid and more sustained when glucose tolerance is ***,GE is influenced by the acute glycaemic environment acute hyperglycaemia slows,while acute hypoglycaemia accelerates *** GE(gastroparesis)occurs frequently in diabetes and critical *** diabetes,this poses challenges for management,particularly in hospitalised individuals and/or those using *** critical illness it compromises the delivery of nutrition and increases the risk of regurgitation and aspiration with consequent lung dysfunction and ventilator *** advances in knowledge relating to GE,which is now recognised as a major determinant of the magnitude of the rise in blood glucose after a meal in both health and diabetes and,the impact of acute glycaemic environment on the rate of GE have been made and the use of gut-based therapies such as glucagon-like peptide-1 receptor agonists,which may profoundly impact GE,in the management of type 2 diabetes,has become *** necessitates an increased understanding of the complex inter-relationships of GE with glycaemia,its implications in hospitalised patients and the relevance of dysglycaemia and its management,particularly in critical *** approaches to management of gastroparesis to achieve more personalised diabetes care,relevant to clinical practice,is *** studies focusing on the interactions of medications affecting GE and the glycaemic environment in hospitalised patients,are required.

关键词： Glycaemia Gastric emptying clinical practice Glucagon-like peptide-1

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Crosstalk between dietary patterns,obesity and nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2022年第27期28卷 3314-3333页

作者： Danijela Ristic-Medic Joanna Bajerska Vesna Vucic Group for nutritional Biochemistry and Dietology Centre of Research Excellence in Nutrition and MetabolismInstitute for Medical ResearchNational Institute of Republic SerbiaBelgrade PO Box 102Serbia Department of Human Nutrition and Dietetics PoznańUniversity of Life SciencesPoznań60-624Poland

The prevalence of nonalcoholic fatty liver disease(NAFLD)is rising worldwide,paralleling the epidemic of *** liver is a key organ for the metabolism of proteins,fats and *** types of fats and carbohydrates in isocaloric diets differently influence fat accumulation in the liver ***,nutrition can manage hepatic and cardiometabolic complications of *** moderately reduced caloric intake,which leads to a weight loss of 5%-10%of initial body weight,is effective in improving liver steatosis and surrogate markers of liver disease *** dietary patterns,the Mediterranean diet mostly prevents the onset of ***,this diet is also the most recommended for the treatment of NAFLD ***,clinical trials based on the dietary interventions in NAFLD patients are *** there are only a few studies examining dietary interventions in clinically advanced stages of NAFLD,such as active and fibrotic steatohepatitis,the optimal diet for patients in these stages of the disease must still be *** this narrative review,we aimed to critically summarize the associations between different dietary patterns,obesity and prevention/risk for NAFLD,to describe specific dietary interventions’impacts on liver steatosis in adults with NAFLD and to provide an updated overview of dietary recommendations that clinicians potentially need to apply in their daily practice.

关键词： Nonalcoholic fatty liver disease Dietary patterns Obesity Diet Mediterranean diet Nutrition Treatment clinical guidance

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Contactins in the central nervous system: role in health and disease

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Neural Regeneration research 2019年第2期14卷 206-216页

作者： Madhurima Chatterjee Detlev Schild Charlotte E.Teunissen Amsterdam UMC VU University Medical Center Department of Clinical Chemistry Amsterdam Neuroscience Institute of Neurophysiology and Cellular Biophysics University of G?ttingen DFG research Center for Nanoscale Microscopy and Molecular physiology of the Brain (CNMPB) University of G?ttingen DFG excellence Cluster 171 University of G?ttingen

Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders.

关键词： cell adhesion molecule Contactins axonal domain,neurogenesis synaptogenesis autism spectrum disorder neuro-developmental disorder neurological disease

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Cardiac stem cells: Current knowledge and future prospects

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World Journal of Stem Cells 2022年第1期14卷 1-40页

作者： Radwa A Mehanna Marwa M Essawy Mona A Barkat Ashraf K Awaad Eman H Thabet Heba A Hamed Hagar Elkafrawy Nehal A Khalil Abeer Sallam Marwa A Kholief Samar S Ibrahim Ghada M Mourad Medical physiology Department/Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt Oral Pathology Department Faculty of Dentistry/Center of Excellence for Research in Regenerative Medicine and ApplicationsFaculty of MedicineAlexandria UniversityAlexandria 21500Egypt Human Anatomy and Embryology Department/Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt Histology and Cell Biology Department/Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt Medical Biochemistry Department/Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt Forensic Medicine and clinical toxicology Department/Center of excellence for research in Regenerative Medicine and Applications Faculty of MedicineAlexandria UniversityAlexandria 21500Egypt

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole *** the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical *** from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of ***,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic *** review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their *** addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other ***,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac ***,the novel role of nanotechnology in cardiac regeneration will be explored.

关键词： Cardiac stem and progenitor cells Cardiac stem cells’secretome Cardiac stem cells’niche and metabolism Nanotechnology clinical trials Combined therapy

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Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

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World Journal of Gastroenterology 2010年第43期16卷 5467-5473页

作者： Sittisak Honsawek Maneerat Chayanupatkul Voranush Chongsrisawat Paisarn Vejchapipat Yong Poovorawan Department of Biochemistry Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Department of physiology Faculty of Medicine Chulalongkorn University Center of excellence in clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University Department of Surgery Faculty of Medicine Chulalongkorn University

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

关键词： Biliary atresia Fibroscan Jaundice Liver stiffness Osteopontin

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Prognostic value of cortisol and thyroid function tests in poisoned patients admitted to toxicology ICU

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World Journal of Emergency Medicine 2018年第1期9卷 51-55页

作者： Shahin Shadnia Nasim Zamani Hossein Hassanian-Moghaddam Hamed Shafaroodi Mina Padandar Mohammad Hasan Rezaeizadeh Toxicological research Center Department of Clinical ToxicologyLoghman Hakim HospitalShahid Beheshti University of Medical Sciences excellence Center of clinical Toxicology Iranian Ministry of Health Pharmaceutical Sciences Branch Islamic Azad University(IAUPS)

BACKGROUND: Prognostic value of cortisol and thyroid function tests(TFTs) has previously been evaluated in medical ICUs. We aimed to evaluate prognostic efficacy of cortisol and TFTs in critically ill poisoned patients admitted to toxicology intensive care unit(ICU).METHODS: In a prospective study of consecutively enrolled subjects admitted to the toxicology ICU, lab analyses included TFTs(total T3 and T4 as well as TSH) and cortisol levels drawn between 8 am–10 am during period of the first 24 hours post-ingestion/exposure. Simplified Acute physiology Score Ⅱ(SAPS Ⅱ) and Acute physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ) were recorded. All scores were compared to detect the best prognostic factor. Type of poisoning was also ***: In 200 patients evaluated, 129 were male and mean age was 31 years. In general, SAPS Ⅱ, T4, and cortisol could prognosticate death. After regression analysis, only cortisol had such efficacy(P=0.04; OR=1.06; 95%CI=1.05–1.08; cut-off=42 μg/d L; sensitivity=70%; specificity=82%). Between aluminium phosphide(ALP)-and non ALP-poisoned patients, level of consciousness, mean arterial pressure, and cortisol level could prognosticate death in ALP poisoning(all Psclinical condition or may be due to their significantly lower blood pressures.

关键词： Prognosis Intensive care unit Cortisol Thyroid function tests Poisoning

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Development of innovative tools for investigation of nutrient-gut interaction

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World Journal of Gastroenterology 2020年第25期26卷 3562-3576页

作者： Wei-Kun Huang Cong Xie Richard L Young Jiang-Bo Zhao Heike Ebendorff-Heidepriem Karen L Jones Christopher K Rayner Tong-Zhi Wu Adelaide Medical School Centre of Research Excellence in Translating Nutritional Science to Good Healththe University of AdelaideAdelaideSA 5005Australia Institute for Photonics and Advanced Sensing School of Physical SciencesUniversity of AdelaideAdelaideSA 5005Australia The ARC centre of excellence for Nanoscale BioPhotonics AdelaideSA 5005Australia Diabetes Nutrition and Gut HealthLifelong HealthSouth Australia Health and Medical Research InstituteAdelaideSA 5005Australia Department of Gastroenterology and Hepatology Royal Adelaide HospitalAdelaideSA 5000Australia Department of Endocrinology Zhongda HospitalInstitute of DiabetesSchool of MedicineSoutheast UniversityNanjing 210009Jiangsu ProvinceChina

The gastrointestinal tract is the key interface between the ingesta and the human *** is wide recognition that the gastrointestinal response to nutrients or bioactive compounds,particularly the secretion of numerous hormones,is critical to the regulation of appetite,body weight and blood *** concept has led to an increasing focus on“gut-based”strategies for the management of metabolic disorders,including type 2 diabetes and *** the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical *** this end,an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine *** review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.

关键词： Nutrient-gut interaction Metabolic disorders Incretin hormones Enteroendocrine cells Enteroids Intestinal intubation Intestine-on-a-chip

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