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Both Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) are highly prevalent worldwide. The emergence of relevant research suggesting a pathogenic linkage between H. pylori infection and MetS-related cardio-cerebrovascular diseases and neurodegenerative disorders, particularly through mechanisms involving brain pericyte deficiency, hyperhomocysteinemia, hyperfibrinogenemia, elevated lipoprotein-a, galectin-3 overexpression, atrial fibrillation, and gut dysbiosis, has raised stimulating questions regarding their pathophysiology and its translational implications for clinicians. An additional stimulating aspect refers to H. pylori and MetS-related activation of innate immune cells, mast cells (MC), which is an important, often early, event in systemic inflammatory pathologies and related brain disorders. Synoptically, MC degranulation may play a role in the pathogenesis of H. pylori and MetS-related obesity, adipokine effects, dyslipidemia, diabetes mellitus, insulin resistance, arterial hypertension, vascular dysfunction and arterial stiffness, an early indicator of atherosclerosis associated with cardio-cerebrovascular and neurodegenerative disorders. Meningeal MC can be activated by triggers including stress and toxins resulting in vascular changes and neurodegeneration. Likewise, H.pylori and MetS-related MC activation is linked with: (a) vasculitis and thromboembolic events that increase the risk of cardio-cerebrovascular and neurodegenerative disorders, and (b) gut dysbiosis-associated neurodegeneration, whereas modulation of gut microbiota and MC activation may promote neuroprotection. This narrative review investigates the intricate relationship between H. pylori infection, MetS, MC activation, and their collective impact on pathophysiological processes linked to neurodegeneration. Through a comprehensive search of current literature, we elucidate the mechanisms through which H. pylori and MetS contribute to MC activation, subsequently triggering cascades of inflammatory responses. This highlights the role of MC as key mediators in the pathogenesis of cardio-cerebrovascular and neurodegenerative disorders, emphasizing their involvement in neuroinflammation, vascular dysfunction and, ultimately, neuronal damage. Although further research is warranted, we provide a novel perspective on the pathophysiology and management of brain disorders by exploring potential therapeutic strategies targeting H. pylori eradication, MetS management, and modulation of MC to mitigate neurodegeneration risk while promoting neuroprotection., Competing Interests: Declaration of competing interest Jannis Kountouras: Declarations of interest: none. Marina Boziki: Declarations of interest: none. Evangelos Kazakos: Declarations of interest: none. Paschalis Theotokis: Declarations of interest: none. Evangelia Kesidou: Declarations of interest: none. Maria Nella: Declarations of interest: none. Christos Bakirtzis: Declarations of interest: none. Eleni Karafoulidou: Declarations of interest: none. Elisabeth Vardaka: Declarations of interest: none. Maria C. Mouratidou: Declarations of interest: none. Foteini Kyrailidi: Declarations of interest: none. Maria Tzitiridou-Chatzopoulou: Declarations of interest: none. Eirini Orovou: Declarations of interest: none. Evaggelia Giartza-Taxidou: Declarations of interest: none. Georgia Deretzi: Declarations of interest: none. Nikolaos Grigoriadis: Declarations of interest: none. Michael Doulberis: Declarations of interest: none., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Helicobacter pylori infection, a significant global burden beyond the gastrointestinal tract, has long been implicated in various systemic pathologies. Rising evidence suggests that the bacterium's intricate relationship with the immune system and its potential to induce chronic inflammation impact diverse pathophysiological processes in pregnant women that may in turn affect the incidence of several adverse pregnancy and neonate outcomes. Helicobacter pylori infection, which has been linked to metabolic syndrome and other disorders by provoking pericyte dysfunction, hyperhomocysteinemia, galectin-3, atrial fibrillation, gut dysbiosis, and mast cell activation pathologies, may also contribute to adverse pregnancy and neonatal outcomes. Together with increasing our biological understanding of the individual and collective involvement of Helicobacter pylori infection-related metabolic syndrome and concurrent activation of mast cells in maternal, fetus, and neonatal health outcomes, the present narrative review may foster related research endeavors to offer novel therapeutic approaches and informed clinical practice interventions to mitigate relevant risks of this critical topic among pregnant women and their offspring.

Metabolic dysfunction-associated fatty liver disease (MAFLD) occurs in a low-grade inflammatory milieu dependent on highly complex networks that span well-beyond the hepatic tissue injury. Dysfunctional systemic metabolism that characterizes the disease, is further induced in response to environmental cues that modify energy and metabolic cellular demands, thereby altering the availability of specific substrates that profoundly regulate, through epigenetic mechanisms, the phenotypic heterogeneity of immune cells and influence hematopoietic stem cell differentiation fate. This immuno-metabolic signaling drives the initiation of downstream effector pathways and results in the decompensation of hepatic homeostasis that precedes pro-fibrotic events. Recent evidence suggests that innate immune cells reside in different tissues in a memory effector state, a phenomenon termed trained immunity, that may be activated by subsequent exogenous (e.g., microbial, dietary) or endogenous (e.g., metabolic, apoptotic) stmuli. This process leads to long-term modifications in the epigenetic landscape that ultimately precondition the cells towards enhanced transcription of inflammatory mediators that accelerates MAFLD development and/or progression. In this mini review we aimed to present current evidence on the potential impact of trained immunity on the pathophysiology of MAFLD, shedding light on the complex immunobiology of the disease and providing novel potential therapeutic strategies to restrain the burden of the disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD), recently renamed as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is a complex, multifactorial disease that progresses via nonalcoholic steatohepatitis (NASH) towards severe liver complications. MAFLD/NAFLD affects up to a third of the global population. It is connected with metabolic syndrome parameters and has been increasing in parallel with the rates of metabolic syndrome parameters worldwide. This disease entity exhibits a strong immune-inflammatory dimension. In MAFLD/NAFLD/NASH, a vast network of innate immune cells is mobilized that can provoke liver damage, leading to advanced fibrosis, cirrhosis and its complications, including hepatocellular carcinoma. However, our understanding of the inflammatory signals that drive the onset and progression of MAFLD/NAFLD/NASH is fragmented. Thus, further investigation is required to better understand the role of specific innate immune cell subsets in the disease, and to aid the design of innovative therapeutic agents to target MAFLD/NAFLD/NASH. In this review, we discuss current concepts regarding the role of innate immune system involvement in MAFLD/NAFLD/NASH onset and progression, along with presenting potential stress signals affecting immune tolerance that may trigger aberrant immune responses. A comprehensive understanding of the innate immune mechanisms involved in MAFLD/NAFLD/NASH pathophysiology will help the discovery of early interventions to prevent the disease, and lead to potential innovative therapeutic strategies that may limit its worldwide burden., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Helicobacter pylori infection consists a high global burden affecting more than 50% of the world's population. It is implicated, beyond substantiated local gastric pathologies, i.e., peptic ulcers and gastric cancer, in the pathophysiology of several neurodegenerative disorders, mainly by inducing hyperhomocysteinemia-related brain cortical thinning (BCT). BCT has been advocated as a possible biomarker associated with neurodegenerative central nervous system disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and/or glaucoma, termed as "ocular Alzheimer's disease". According to the infection hypothesis in relation to neurodegeneration, Helicobacter pylori as non-commensal gut microbiome has been advocated as trigger and/or mediator of neurodegenerative diseases, such as the development of Alzheimer's disease. Among others, Helicobacter pylori -related inflammatory mediators, defensins, autophagy, vitamin D, dietary factors, role of probiotics, and some pathogenetic considerations including relevant involved genes are discussed within this opinion article. In conclusion, by controlling the impact of Helicobacter pylori -related hyperhomocysteinemia on neurodegenerative disorders might offer benefits, and additional research is warranted to clarify this crucial topic currently representing a major worldwide burden.