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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos j.Arauzo-Bravo Daniela Gerovska matthias Schwab Alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(AlS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fAlS),most cases are considered sporadic(sAlS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.lee Ryota l.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

Can a polymorphism in the thalassemia gene and a heterozygote CFTR mutation cause acute pancreatitis?

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World journal of Clinical Cases 2014年第3期2卷 62-66页

作者： j.matthias l?hr Stephan Haas Gastrocentrum Karolinska Institutet and University Hospital Division of Molecular Gastroenterology Department of Medicine Ⅱ Medical Faculty Mannheim University of Heidelberg

The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator(CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.

关键词： Acute pancreatitis Hypoxia Flying Thalassemia Hemoglobin Cystic fibrosis transmembrane conductance regulator Hereditary persistence of fetal hemoglobin

Extravascular use of drug-eluting beads: A promising approach in compartment-based tumor therapy

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World journal of Gastroenterology 2013年第43期19卷 7586-7593页

作者： Simon Binder Andrew l lewis j.matthias lhr Michael Keese Faculty of Medicine Mannheim University of Heidelberg68167 MannheimGermany Biocompatibles UK ltd. Department for Research and DevelopmentFarnham GU98QL SurreyUnited Kingdom Karolinska Institute Department of Clinical ScienceIntervention and Technology17177 StockholmSweden Clinic for Vascular and Endovascular Surgery University Hospital Frankfurt60590 Frankfurt am MainGermany

Intraperitoneal carcinomatosis(PC)may occur with several tumor *** prognosis of patients suffering from PC is usually *** treatment depends on the cancer entity and includes systemic chemotherapy,radiation therapy,hormonal therapy and surgical *** few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor *** therapies are often accompanied by severe systemic *** approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier *** experimental results have been achieved using drug-eluting beads(DEBs).A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular *** encapsulation devices were able to harbor CYP2B1producing cells and to shield them from the hosts immune system when injected *** this way ifosfamide-which is transformed into its active metabolites by CYP2B1-could be successfully targeted into pancreatic tumor *** DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of *** CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled,DEBs will become promising tools in compartmentbased anticancer treatment.

关键词： Compartment based therapy Intraperitoneal Drug-eluting beads Carcinomatosis Hyperthermic intraperitoneal chemotherapy Glioblastoma Pancreatic cancer CYP2B1 Ifosfamide

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage Mark l.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation

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World journal of Gastroenterology 2006年第30期12卷 4843-4849页

作者： Stephan l Haas Ralf jesnowski Michael Steiner Frank Hummel jrg Ringel Christine Burstein Horst Nizze Stefan liebe j.matthias lhr Department of Medicine II University of Heidelberg at Mannheim Germany Department of Clinical Chemistry and Pathobiochemistry University of Rostock Rostock Germany Department of Pathology University of Rostock Rostock Germany Department of Medicine University of Rostock Rostock Germany

AIM： To study expression of tissue factor （TF） in pancreatic cancer and its role in the development of thromboembolism.METHODS： TF expression was studied in eight human pancreatic carcinoma cell lines by Northern blot and indirect immunofluorescence. Expression of alternatively spliced TF （asTF） was assessed by RT-PCR. In addition, TF expression was determined by immunofluorescence in pancreatic tissues of 19 patients with pancreatic adenocarcinoma （PCa）, 9 patients with chronic pancreatitis （CP） and 20 normal controls. Plasma samples （30 PCa-patients, 13 CP-patients and 20 controls） were investigated for soluble TF levels and coagulation activation markers [thrombin-antithrombin Ⅲ complex （TAT）, prothrombin fragment 1 ＋ 2 （F1 ＋ 2）]. RESUlTS： All pancreatic carcinoma cell lines expressed TF （8/8） and most of them expressed asTF （6/8）. TF expression at the protein level did not correlate with the differentiation of the carcinoma cell line. All but two pancreatic cancer tissue samples stained positive for TF （17/19）. In all samples of CP weak staining was restricted to pancreatic duct cells, whereas only a few subendothelial cells were positive in 9/20 of normal controls. TF and TAT levels in PCa patients were significantly elevated compared to controls whereas elevated F1 ＋ 2 levels did not reach statistical significance compared to controls. In CP patients TAT and F1 ＋ 2 levels proved to be significantly elevated compared to controls, although TAT elevation was less pronounced than in PCa patients. CONClUSION： We conclude that in addition to the upregulated expression of TF on the cell membrane, soluble TF might contribute to activation of the coagulation system in pancreatic cancer.

关键词： Coagulation activation Pancreatic carcinoma Thromboembolism Thrombosis Tissue factor

Zinc deficiency in patients with chronic pancreatitis

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World journal of Gastroenterology 2019年第5期25卷 600-607页

作者： Miroslav Vujasinovic AleksANDra Hedstr?m Patrick Maisonneuve Roberto Valente Henrik von Horn j.matthias l?hr Stephan l Haas Department for Digestive Diseases Karolinska University Hospital Division of Epidemiology and Biostatistics IEO European Institute of Oncology IRCCS Department for Digestive Diseases Sapienza University of Rome Division of Clinical Chemistry Department of Molecular Medicine and Surgery Karolinska Institutet Karolinska University Hospital Department of Clinical Science Intervention and Technology (CLINTEC)Karolinska Institute

BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency(PEI),which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting *** To investigate serum zinc levels in patients with CP of various *** Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the MANNHEIM classification system into the following etiological subcategories:alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal(fecal elastase 1 > 200 μg/g), mildly reduced(100-200μg/g) and severely reduced(fecal elastase 1 lTS A total of 150 patients were included in the analysis. Zinc deficiency(l/l) was present in 39(26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency(FE-1 lder age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients 0.002]. Smoking and number of packyears were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher

关键词： Zinc Pancreas Pancreatic exocrine insufficiency Chronic pancreatitis Malnutrition

Pancreatic cancer–Outlook: gene therapy

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The Chinese-German journal of Clinical Oncology 2007年第2期6卷 181-186页

作者： j.-matthias lhr Molecular Gastroenterology Unit German Cancer Research Center (DKFZ) and Department of Medicine II Mannheim Medical Faculty University of Heidelberg Theodor Kutzer Ufer 1-3 68167 Mannheim Germany

Gene therapy offers an elegant alternative to toxic chemotherapy regimens, mostly without severe side effects. Cancer gene therapy was among the first applications. Following the enthusiasm in the early nineties, a more rationale view is the recent way to look at it. This tutorial review looks upon the tools of gene therapy and the principte elements （vector, promoter, targeting, therapeutic gene）. The principles of gene therapy such as gene directed enzyme prodrug therapy （GDEPT） and gene directed tumor vaccination are explained. Further, published protocols and clinical studies for pancreatic carcinoma gene therapy are reviewed. Finally, an outlook is given on the latest developments, some of them beyond conventional gene therapy.

关键词： cancer gene therapy review tutorial pancreatic cancer

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james l.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic