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      Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice

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          Abstract

          There are currently insufficient anthelmintic medications available for the treatment of toxocariasis. For instance, Albendazole (ABZ) is the preferred medication, but its effectiveness against tissue-dwelling parasites is limited. In addition, Metformin (MTF) is a widely used oral antidiabetic medication that is considered to be safe for treatment. This study aimed to investigate any potential effects of MTF, alone or in combination with ABZ, on mice infections caused by Toxocara canis ( T. canis). The efficacy of the treatment was assessed in the acute and chronic phases of the infection by larval recovery and histopathological, immunohistochemical, and biochemical studies. The results showed that combined therapy significantly reduced larval counts in the liver, brain, and muscles and ameliorated hepatic and brain pathology. It reduced oxidative stress and TGF-β mRNA expression and increased FGF21 levels in the liver. It decreased TNF-α levels and MMP-9 expression in the brain. In addition, it increased serum levels of IL-12 and IFN-γ and decreased serum levels of IL-4 and IL-10. In the acute and chronic phases of the infection, the combined treatment was more effective than ABZ alone. In conclusion, this study highlights the potential role of MTF as an adjuvant in the treatment of experimental T. canis infection when administered with ABZ.

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          The role of inflammation in CNS injury and disease.

          For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.
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            Metformin: from mechanisms of action to therapies.

            Metformin is currently the first-line drug treatment for type 2 diabetes. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin's mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug. Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Non-Smad Signaling Pathways of the TGF-β Family.

              Ying Zhang (2017)
              Transforming growth factor β (TGF-β) and structurally related factors use several intracellular signaling pathways in addition to Smad signaling to regulate a wide array of cellular functions. These non-Smad signaling pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. This review summarizes the current knowledge of the mechanisms by which non-Smad signaling pathways are directly activated in response to ligand binding, how activation of these pathways impinges on Smads and non-Smad targets, and how final cellular responses are affected in response to these noncanonical signaling modes.
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                Author and article information

                Contributors
                dina.elgendy@med.tanta.edu.eg , drdina83@yahoo.com
                Journal
                Parasitol Res
                Parasitol Res
                Parasitology Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0932-0113
                1432-1955
                24 October 2023
                24 October 2023
                2023
                : 122
                : 12
                : 3213-3231
                Affiliations
                [1 ]Medical Parasitology Department, Faculty of Medicine, Tanta University, ( https://ror.org/016jp5b92) Tanta, Egypt
                [2 ]Zoology Department, Faculty of Science, Tanta University, ( https://ror.org/016jp5b92) Tanta, 31527 Egypt
                [3 ]Medical Biochemistry Department, Faculty of Medicine, Tanta University, ( https://ror.org/016jp5b92) Tanta, Egypt
                [4 ]Pathology Department, Faculty of Medicine, Tanta University, ( https://ror.org/016jp5b92) Tanta, Egypt
                [5 ]Medical Pharmacology Department, Faculty of Medicine, Tanta University, ( https://ror.org/016jp5b92) Tanta, Egypt
                Author notes

                Handling Editor: Una Ryan

                Author information
                https://orcid.org/0000-0002-6754-6214
                https://orcid.org/0000-0003-0487-5659
                https://orcid.org/0000-0002-8230-6761
                https://orcid.org/0000-0001-7707-1796
                https://orcid.org/0000-0002-0070-6113
                Article
                8011
                10.1007/s00436-023-08011-1
                10667394
                37874393
                38b24356-42eb-4ded-9ac7-6fefd067248c
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 June 2023
                : 12 October 2023
                Funding
                Funded by: Tanta University
                Categories
                Research
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Parasitology
                toxocara canis,albendazole,metformin,mmp-9,oxidative stress,fgf21,tnf-α,il-12,ifn-γ,il-4,il-10; tgf-β
                Parasitology
                toxocara canis, albendazole, metformin, mmp-9, oxidative stress, fgf21, tnf-α, il-12, ifn-γ, il-4, il-10; tgf-β

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