Potential impact of trained innate immunity on the pathophysiology of metabolic dysfunction-associated fatty liver disease.

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.

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration.

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.

Max Scheler's influence on Kurt Schneider.

Kurt Schneider (1887-1967) met Max Scheler (1874-1928) in 1919 when he enrolled in the latter's philosophy seminars at the University of Cologne. Kurt Schneider was then a junior psychiatrist and Max Scheler a renowned philosophy professor and co-founder of the phenomenological movement in philosophy. We uncover the facts about their intellectual and personal relationship, summarize the main articles and books that they wrote and consider whether Max Scheler did influence the young Kurt Schneider. We conclude that Scheler's philosophy of emotion impressed Schneider, and that the latter's notion of 'vital depression' as the core element in melancholia was essentially applied Schelerian philosophy. Schneider's more celebrated contributions to psychiatry - his notion of first rank symptoms of schizophrenia - owed nothing to Scheler or any other philosopher.

The Role of Helicobacter pylori and Metabolic Syndrome-Related Mast Cell Activation Pathologies and Their Potential Impact on Pregnancy and Neonatal Outcomes.

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.

Impact of Helicobacter pylori and metabolic syndrome on mast cell activation-related pathophysiology and neurodegeneration.

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.

Association between Helicobacter pylori Infection and Nasal Polyps: A Systematic Review and Meta-Analysis.

BACKGROUND: Helicobacter pylori (H. pylori) has definite or possible associations with multiple local and distant manifestations. H. pylori has been isolated from multiple sites throughout the body, including the nose. Clinical non-randomized studies with H. pylori report discrepant data regarding the association between H. pylori infection and nasal polyps. The aim of this first systematic review and meta-analysis was the assessment of the strength of the association between H. pylori infection and incidence of nasal polyps. METHODS: We performed an electronic search in the three major medical databases, namely PubMed, EMBASE and Cochrane, to extract and analyze data as per PRISMA guidelines. RESULTS: Out of 57 articles, 12 studies were graded as good quality for analysis. Male-to-female ratio was 2:1, and age ranged between 17-78 years. The cumulative pooled rate of H. pylori infection in the nasal polyp group was 32.3% (controls 17.8%). The comparison between the two groups revealed a more significant incidence of H. pylori infection among the nasal polyp group (OR 4.12), though with high heterogeneity I2 = 66%. Subgroup analysis demonstrated that in European studies, the prevalence of H. pylori infection among the nasal polyp group was significantly higher than in controls, yielding null heterogeneity. Subgroup analysis based on immunohistochemistry resulted in null heterogeneity with preserving a statistically significant difference in H. pylori infection prevalence between the groups. CONCLUSION: The present study revealed a positive association between H. pylori infection and nasal polyps.

Innate immunity and nonalcoholic fatty liver disease.

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.

Differential Expression of Drosophila Transgelins Throughout Development.

Transgelins are a conserved family of actin-binding proteins involved in cytoskeletal remodeling, cell contractility, and cell shape. In both mammals and Drosophila, three genes encode transgelin proteins. Transgelins exhibit a broad and overlapping expression pattern, which has obscured the precise identification of their role in development. Here, we report the first systematic developmental analysis of all Drosophila transgelin proteins, namely, Mp20, CG5023, and Chd64 in the living organism. Drosophila transgelins display overall higher sequence identity with mammalian TAGLN-3 and TAGLN-2 than with TAGLN. Detailed examination in different developmental stages revealed that Mp20 and CG5023 are predominantly expressed in mesodermal tissues with the onset of myogenesis and accumulate in the cytoplasm of all somatic muscles and heart in the late embryo. Notably, at postembryonic developmental stages, Mp20 and CG5023 are detected in the gut's circumferential muscles with distinct subcellular localization: Z-lines for Mp20 and sarcomere and nucleus for CG5023. Only CG5023 is strongly detected in the adult fly in the abdominal, leg, and synchronous thoracic muscles. Chd64 protein is primarily expressed in endodermal and ectodermal tissues and has a dual subcellular localization in the cytoplasm and the nucleus. During the larval-pupae transition, Chd64 is expressed in the brain, eye, legs, halteres, and wings. In contrast, in the adult fly, Chd64 is expressed in epithelia, including the alimentary tract and genitalia. Based on the non-overlapping tissue expression, we predict that Mp20 and CG5023 mostly cooperate to modulate muscle function, whereas Chd64 has distinct roles in epithelial, neuronal, and endodermal tissues.

Red Blood Cell Transfusions in Greece: Results of a Survey of Red Blood Cell Use in 2013.

OBJECTIVE: Greece is ranked as the second highest consumer of blood components in Europe. For an effective transfusion system and in order to reduce variability of transfusion practice by implementing evidence-based transfusion guidelines it is necessary to study and monitor blood management strategies. Our study was conducted in order to evaluate the use of red blood cell units (RBC-U) in nationwide scale mapping parameters that contribute to their proper management in Greece. MATERIALS AND METHODS: The survey was conducted by the Working Committee of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology from January to December 2013. The collected data included the number, ABO/D blood group, patients' department, and storage age of RBC-U transfused. RESULTS: The number of RBC-U evaluated was 103,702 (17.77%) out of 583,457 RBC-U transfused in Greece in 2013. RBC-U transfused by hospital department (mean percentage) was as follows: Surgery 29.34%, Internal Medicine 29.48%, Oncology/Hematology 14.65%, Thalassemia 8.87%, Intensive Care Unit 6.55%, Nephrology 1.78%, Obstetrics/Gynecology 1.46%, Neonatal&Pediatric 0.31%, Private Hospitals 8.57%. RBC-U distribution according to ABO/D blood group was: A: 39.02%, B: 12.41%, AB: 5.16%, O: 43.41%, D+: 87.99%, D-: 12.01%. The majority of RBC-U (62.46%) was transfused in the first 15 days of storage, 25.24% at 16 to 28 days, and 12.28% at 29-42 days. CONCLUSION: Despite a high intercenter variability in RBC transfusions, surgical and internal medicine patients were the most common groups of patients transfused with an increasing rate for internal medicine patients. The majority of RBC-U were transfused within the first 15 days of storage, which is possibly the consequence of blood supply insufficiency leading to the direct use of fresh blood. Benchmarking transfusion activity may help to decrease the inappropriate use of blood products, reduce the cost of care, and optimize the use of the voluntary donor's gift.

Structure-function analysis of protein complexes involved in the molecular architecture of juxtaparanodal regions of myelinated fibers.

Demyelinating disorders, including multiple sclerosis (MS), are common causes of neurological disability. One critical step towards the management and therapy of demyelinating diseases is to understand the basic functions of myelinating glia and their relationship with axons. Axons and myelinating glia, oligodendrocytes in the central (CNS) and Schwann cells in the peripheral (PNS) nervous systems, reciprocally influence each other's development and trophism. These interactions are critical for the formation of distinct axonal domains in myelinated fibers that ensure the rapid propagation of action potentials. Macromolecular complexes mediating axo-glial interactions in these domains have been identified, consisting of members of the immunoglobulin superfamily (IgSF) of adhesion molecules and the neurexin/NCP superfamily as well as other proteins. We have investigated the molecular details of axo-glial interactions in the juxtaparanodal region of myelinated fibers by utilizing domain-specific GFP constructs and immunoprecipitation assays on transfected cells. We have shown that the immunoglobulin domains of the IgSF member TAG-1/Cnt-2 are necessary and sufficient for the direct, cis interaction of this protein with Caspr2 and potassium channels.