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Adeno-associated virus mediated delivery of Tregitope 167 ameliorates experimental colitis

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World Journal of Gastroenterology 2012年第32期18卷 4288-4299页

作者： Sander van der Marel Anna Majowicz Karin Kwikkers Richard van Logtenstein Anje A te Velde Anne S De Groot Sybren L Meijer Sander J van Deventer harald petry Daniel W Hommes Valerie Ferreira Department of Research and Development uniQure B.V.1105 BA AmsterdamThe Netherlands Department of Gastroenterology and Hepatology Leiden University Medical Center2333 ZA LeidenThe Netherlands Tytgat Institute for Liver and Intestinal Research Academic Medical CenterUniversity of Amsterdam1105 BK AmsterdamThe Netherlands EpiVax Inc. ProvidenceRI 02903United States The Institute for Immunology and Informatics University of Rhode IslandKingstonRI 02881United States Department of Pathology Academic Medical CenterUniversity of Amsterdam1105 AZ AmsterdamThe Netherlands Center for Inflammatory Bowel Diseases UCLA Health SystemLos AngelesCA 90095United States

AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis ***:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c *** after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d *** groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were *** staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated ***:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of *** contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ *** both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelia

关键词： Adeno-associated virus Regulatory T cell epitope Inflammatory bowel diseases Adeno-associated virus

Thirteen years to get from b to a:one of the neglected isoforms of IL-37 enters the stage

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Cellular & Molecular Immunology 2024年第2期21卷 201-202页

作者： Steven X.Cho Ina Rudloff Andrew M.Ellisdon Claudia A.Nold-petry Marcel F.Nold Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Pediatrics Monash UniversityMelbourneVICAustralia Cancer Program Biomedicine Discovery InstituteMonash UniversityMelbourneVICAustralia Monash Newborn Monash Children’s HospitalMelbourneVICAustralia

Interleukin(IL)-37 is one of the few anti-inflammatory members of the predominantly pro-inflammatory IL-1 cytokine ***-37 possesses alarmin-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent mechanisms,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum“peacemaking”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflammatory therapeutics[5,6].

关键词： Interleukin neglected cytokine

Gene and cell therapy based treatment strategies for inflammatory bowel diseases

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World Journal of Gastrointestinal Pathophysiology 2011年第6期2卷 114-122页

作者： Sander van der Marel Anna Majowicz Sander van Deventer harald petry Daniel W Hommes Valerie Ferreira Department of Research and Development Amsterdam Molecular Therapeutics BV1105 BA AmsterdamThe Netherlands Department of Gastroenterology and Hepatology Leiden University Medical Center2333 ZA LeidenThe Netherlands

Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young *** available therapies can result in induction and maintenance of remission,but are not curative and have sometimes important side *** in basic research in IBD have provided new therapeutic opportunities to target the inflammatory process *** and cell therapy approaches are suitable to prevent inflammation in the gastrointestinal tract and show therefore potential in the treatment of *** this review,we present the current progress in the field of both gene and cell therapy and future prospects in the context of *** gene therapy,we focus on viral vectors and their applications in preclinical *** focus for cell therapy is on regulatory T lymphocytes and mesenchymal stromal cells,their potential for the treatment of IBD and the progress made in both preclinical models and clinical trials.

关键词： Viral vector Gene therapy Cell therapy Inflammatory bowel diseases Immune tolerance Regulatory T lymphocytes Mesenchymal stromal cells

Comparing Gravitation in Flat Space-Time with General Relativity

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Journal of Modern Physics 2016年第12期7卷 1492-1499页

作者： Walter petry Mathematical Institute University of Düsseldorf Düsseldorf Germany

General relativity (GR) and gravitation in flat space-time (GFST) are covariant theories to describe gravitation. The metric of GR is given by the form of proper-time and the metric of GFST is the flat space-time form different from that of proper-time. GR has as source the matter tensor and the Einstein tensor describes the gravitational field whereas the source of GFST is the total energy-momentum including gravitation and the field is described by a non-linear differential operator of order two in divergence form. The results of the two theories agree for weak gravitational fields to the order of measurable accuracy. It is well-known that homogeneous, isotropic, cosmological models of GR start from a point singularity of the universe, the so called big bang. The density of matter is infinite. Therefore, our observable universe implies an expansion of space, in particular an inflationary expansion in the beginning. This is the presently most accepted model of the universe although doubts exist because infinities don’t exist in physics. GFST starts in the beginning from a homogeneous, isotropic universe with uniformly distributed energy and no matter. In the course of time, matter is created out of energy where the total energy is conserved. There is no singularity. The space is flat and the space may be non-expanding.

关键词： Gravitation Cosmology Flat Space No Singularity Non-Expanding Universe

Cosmology with Bounce by Flat Space-Time Theory of Gravitation and a New Interpretation

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Journal of Modern Physics 2013年第7期4卷 20-25页

作者： Walter petry Mathematisches Institut der Universitaet Duesseldorf Duesseldorf Germany

General relativity predicts a singularity in the beginning of the universe being called big bang. Recent developments in loop quantum cosmology avoid the singularity and the big bang is replaced by a big bounce. A classical theory of gravitation in flat space-time also avoids the singularity under natural conditions on the density parameters. The universe contracts to a positive minimum and then it expands during all times. It is not symmetric with regard to its minimum implying a finite age measured with proper time of the universe. The space of the universe is flat and the total energy is conserved. Under the assumption that the sum of the density parameters is a little bit bigger than one the universe is very hot in early times. Later on, the cosmological model agrees with the one of general relativity. A new interpretation of a non-expanding universe may be given by virtue of flat space-time theory of gravitation.

关键词： Gravitation Cosmology Big Bounce Flat Space No Big Bang Non-Expanding Universe

Gravitation in Flat Space-Time and Black Holes

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Journal of Modern Physics 2014年第16期5卷 1553-1559页

作者： Walter petry Mathematical Institute of the University Duesseldorf Duesseldorf Germany

Static, spherically symmetric bodies are studied by the use of flat space-time theory of gravitation. In empty space a singularity at a Euclidean distance from the centre can exist. But the radius of this singular sphere is smaller than the radius of the body. Hence, there is no event horizon, i.e. black holes do not exist. Escape of energy and information is possible. Flat space-time theory of gravitation and quantum mechanics do not contradict to one another.

关键词： Gravitation Flat Space-Time Spherical Symmetry Black Holes

Gravitation as Geometry or as Field

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Journal of Applied Mathematics and Physics 2017年第4期5卷 862-872页

作者： Walter petry Mathematical Institute of the University Duesseldorf Duesseldorf Germany

General relativity (GR) and gravitation in flat space-time (GFST) are covariant theories to describe gravitation. The metric of GR is given by the form of proper-time and the metric of GFST is a flat space-time form different from that of proper-time. The source of GR is the matter tensor and the Einstein tensor describes the gravitational field. The source of GFST is the total energymomentum including gravitation. The field is described by a non-linear differential operator of order two in divergence form. The results of the two theories agree for weak gravitational fields to the order of measurable accuracy. It is well-known that homogeneous, isotropic, cosmological models of GR start from a point singularity of the universe, the so called big bang. The density of matter is infinite. Therefore, our observable big universe implies an expansion of space, in particular an inflationary expansion in the beginning. Doubts are stated because infinities don’t exist in physics. An explanation to the present, controversial discussion of expanding accelerating or non-accelerating universe as well as non-expanding universe is given. GFST starts in the beginning from a homogeneous, isotropic universe with uniformly distributed energy and no matter. In the course of time matter is created out of energy where the total energy is conserved. There is no singularity, i.e. no big bang. The space is flat and non-expanding.

关键词： Gravitation Cosmology Flat Space No Singularity No Big Bang Non-Expanding Universe

The Hubble Constant Problem and the Solution by Gravitation in Flat Space-Time

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Journal of Modern Physics 2020年第2期11卷 214-220页

作者： Walter petry Mathematical Institute of the University Düsseldorf DüsseldorfGermany

General Relativity implies an expanding Universe from a singularity, the so-called Big Bang. The rate of expansion is the Hubble constant. There are two major ways of measuring the expansion of the Universe: through the cosmic distance ladder and through looking at the signals originated from the beginning of the Universe. These two methods give quite different results for the Hubble constant. Hence, the Universe doesn’t expand. The solution to this problem is the theory of gravitation in flat space-time where space isn’t expanding. All the results of gravitation for weak fields of this theory agree with those of General Relativity to measurable accuracy whereas at the beginning of the Universe the results of both theories are quite different, i.e. no singularity by gravitation in flat space-time and non-expanding universe, and a Big Bang (singularity) by General Relativity.

关键词： Gravitation in Flat Space-Time Cosmological Models Hubble Constant No Big Bang No Singularity Non-Expanding Universe

Gravitational Energy and No Big Bang Starts the Universe

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Journal of Modern Physics 2018年第7期9卷 1441-1447页

作者： Walter petry Mathematical Institute University of Duesseldorf Duesseldorf Germany

Gravitation in flat space-time is described as field and studied in several articles. In addition to the flat space-time metric a quadratic form formally similar to that of general relativity defines the proper-time. The field equations for the gravitational field are non-linear differential equations of second order in divergence form and have as source the total energy-momentum tensor (inclusive that of gravitation). The total energy-momentum is conserved. It implies the equations of motion for matter in this field. The application of the theory gives for weak fields to measurable accuracy the same results as general relativity. The results of cosmological models are quite different from those of general relativity. The beginning of the universe starts from uniformly distributed gravitational energy without matter and radiation which is generated in the course of time. The solution is given in the pseudo-Euclidean metric, i.e. space is flat and non-expanding. There are non-singular solutions, i.e. no big bang. The redshift is a gravitational effect and not a Doppler effect. Gravitation is explained as field with attractive property and the condensed gravitational field converts to matter, radiation, etc. in the universe whereas the total energy is conserved. There is no contraction and no expansion of the universe.

关键词： Gravitation Flat Space-Time Cosmology No Singularity No Big Bang Non-Expanding Universe No Doppler Effect