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.

Ofeleein i mi Vlaptin-Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic.

The persistence of the coronavirus disease 2019 (COVID-19) pandemic has triggered research into limiting transmission, morbidity and mortality, thus warranting a comprehensive approach to guide balanced healthcare policies with respect to people's physical and mental health. The mainstay priority during COVID-19 is to achieve widespread immunity, which could be established through natural contact or vaccination. Deep knowledge of the immune response combined with recent specific data indicates the potential inferiority of induced immunity against infection. Moreover, the prevention of transmission has been founded on general non-pharmacological measures of protection, albeit debate exists considering their efficacy and, among other issues, their socio-psychological burden. The second line of defense is engaged after infection and is supported by a plethora of studied agents, such as antibiotics, steroids and non-steroid anti-inflammatory drugs, antiviral medications and other biological agents that have been proposed, though variability in terms of benefits and adverse events has not allowed distinct solutions, albeit certain treatments might have a role in prevention and/or treatment of the disease. This narrative review summarizes the existing literature on the advantages and weaknesses of current COVID-19 management measures, thus underlining the necessity of acting based on the classical principle of "ofeleein i mi vlaptin", that is, to help or not to harm.

Early life triggers for food allergy that in turn impacts dietary habits in childhood.

INTRODUCTION AND OBJECTIVES: In order to investigate food allergy's prevalence, risk factors and eating behavior of children with relevant anamnesis, a study was performed in Cypriot primary schools. PATIENTS: A specially composed questionnaire for self-reported adverse reactions to food, created in the context of the EuroPrevall study, was distributed in 13 representative primary schools across the country. Participants were sub-grouped into three groups; healthy (H), those with unconfirmed food hypersensitivity reactions (FA-) and children with a confirmed diagnosis by a physician IgE-mediated food allergy (FA+). Food habits, family health history and lifestyle factors were assessed and groups' outcomes were compared with each other. RESULTS: For the study, 202 questionnaires were completed and returned; 31 children (19 FA- and 12 FA+) reported an adverse food reaction. Significant risk factors for developing FA+ were being the first born or having siblings with asthma, attended a day nursery, but also maternal alcohol drinking during pregnancy, parental smoking and parental occupation in food processing or use of latex gloves. The presence of children in the kitchen during cooking showed a protective role. Dietary habits of FA+ children were significantly diminished in terms of variety and frequency of consumption in comparison to the rest, in which had a greater overlap. CONCLUSION: Further research is required for the interesting risk or protective factors revealing from the current investigation. The negative effect of food allergy in the dietary habits of food allergic children documented in the literature, is strongly supported herein.

Implementation of the Water Framework Directive: Lessons Learned and Future Perspectives for an Ecologically Meaningful Classification Based on Phytoplankton of the Status of Greek Lakes, Mediterranean Region.

The enactment of the Water Framework Directive (WFD) initiated scientific efforts to develop reliable methods for comparing prevailing lake conditions against reference (or nonimpaired) states, using the state of a set biological elements. Drawing a distinction between impaired and natural conditions can be a challenging exercise. Another important aspect is to ensure that water quality assessment is comparable among the different Member States. In this context, the present paper offers a constructive critique of the practices followed during the WFD implementation in Greece by pinpointing methodological weaknesses and knowledge gaps that undermine our ability to classify the ecological quality of Greek lakes. One of the pillars of WDF is a valid lake typology that sets ecological standards transcending geographic regions and national boundaries. The national typology of Greek lakes has failed to take into account essential components. WFD compliance assessments based on the descriptions of phytoplankton communities are oversimplified and as such should be revisited. Exclusion of most chroococcal species from the analysis of cyanobacteria biovolume in Greek lakes/reservoirs and most reservoirs in Spain, Portugal, and Cyprus is not consistent with the distribution of those taxa in lakes. Similarly, the total biovolume reference values and the indices used in classification schemes reflect misunderstandings of WFD core principles. This hampers the comparability of ecological status across Europe and leads to quality standards that are too relaxed to provide an efficient target for the protection of Greek/transboundary lakes such as the ancient Lake Megali Prespa.

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.

Microbiota and Cyanotoxin Content of Retail Spirulina Supplements and Spirulina Supplemented Foods.

Cyanobacterial biomass such as spirulina (Arthrospira spp.) is widely available as a food supplement and can also be added to foods as a nutritionally beneficial ingredient. Spirulina is often produced in open ponds, which are vulnerable to contamination by various microorganisms, including some toxin-producing cyanobacteria. This study examined the microbial population of commercially available spirulina products including for the presence of cyanobacterial toxins. Five products (two supplements, three foods) were examined. The microbial populations were determined by culture methods, followed by identification of isolates using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), and by 16S rRNA amplicon sequencing of the products themselves and of the total growth on the enumeration plates. Toxin analysis was carried out by enzyme-linked immunosorbent assay (ELISA). Several potentially pathogenic bacteria were detected in the products, including Bacillus cereus and Klebsiella pneumoniae. Microcystin toxins were detected in all the products at levels that could lead to consumers exceeding their recommended daily limits. Substantial differences were observed in the identifications obtained using amplicon sequencing and MALDI-TOF, particularly between closely related Bacillus spp. The study showed that there are microbiological safety issues associated with commercial spirulina products that should be addressed, and these are most likely associated with the normal means of production in open ponds.

Effect of spironolactone on pharmacological treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) was recently renamed to metabolic (dysfunction)-associated fatty liver disease (MAFLD) to better characterize its pathogenic origin. NAFLD represents, at least in western societies, a potential epidemic with raising prevalence. Its multifactorial pathogenesis is partially unraveled and till now there is no approved pharmacotherapy for NAFLD. A plethora of various choices are investigated in clinical trials, targeting an arsenal of different pathways and molecules. Since the mineralocorticoid receptor (MR) and renin-angiotensin-aldosterone system (RAAS) appear to be implicated in NAFLD, within this concise review, we focus on a rather classical and inexpensive pharmacological agent, spironolactone. We present the current lines of evidence of MR and RAAS-related preclinical models and human trials reporting an association with NAFLD. In conclusion, evidence about spironolactone of RAAS is commented, as potential future pharmacological management of NAFLD.

Impact of nonalcoholic fatty liver disease-related metabolic state on depression.

Nonalcoholic fatty liver disease (NAFLD), also recently referred as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by hepatocyte steatosis in the setting of metabolic risk conditions and in the absence of an underlying precursor, for instance alcohol consumption, hepatotropic viruses and hepatotoxic drugs. A possible association between NAFLD and depression has been proposed, owing to intersecting pathophysiological pathways. This narrative review aimed to summarize the current evidence that illustrate the potential pathophysiological and clinical linkage between NAFLD-related metabolic state and depression. Prefrontal cortex lesions are suggested to be a consequence of liver steatosis-associated systematic hyperinflammatory state, a phenomenon also occurring in depression. In addition, depressive symptoms are present in neurotransmitter imbalances. These abnormalities seem to be correlated with NAFLD/MAFLD, in terms of insulin resistance (IR), ammonia and gut dysbiosis' impact on serotonin, dopamine, noradrenaline levels and gamma aminobutyric acid receptors. Furthermore, reduced levels of nesfatin-1 and copine-6-associated BDNF (brain-derived neurotrophic factor) levels have been considered as a probable link between NAFLD and depression. Regarding NAFLD-related gut dysbiosis, it stimulates mediators including lipopolysaccharides, short-chain fatty acids and bile acids, which play significant role in depression. Finally, western diet and IR, which are mainstay components of NAFLD/MAFLD, are, also, substantiated to affect neurotransmitters in hippocampus and produce neurotoxic lipids that contribute to neurologic dysfunction, and thus trigger emotional disturbances, mainly depressive symptoms.

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.

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension.

Arterial hypertension is a risk factor for several pathologies, mainly including cardio-cerebrovascular diseases, which rank as leading causes of morbidity and mortality worldwide. Arterial hypertension also constitutes a fundamental component of the metabolic syndrome. Helicobacter pylori infection is one of the most common types of chronic infection globally and displays a plethora of both gastric and extragastric effects. Among other entities, Helicobacter pylori has been implicated in the pathogenesis of the metabolic syndrome. Within this review, we illustrate the current state-of-the-art evidence, which may link several components of the Helicobacter pylori-related metabolic syndrome, including non-alcoholic fatty liver disease and arterial hypertension. In particular, current knowledge of how Helicobacter pylori exerts its virulence through dietary, inflammatory and metabolic pathways will be discussed. Although there is still no causative link between these entities, the emerging evidence from both basic and clinical research supports the proposal that several components of the Helicobacter pylori infection-related metabolic syndrome present an important risk factor in the development of arterial hypertension. The triad of Helicobacter pylori infection, the metabolic syndrome, and hypertension represents a crucial worldwide health problem on a pandemic scale with high morbidity and mortality, like COVID-19, thereby requiring awareness and appropriate management on a global scale.

The trimebutine effect on Helicobacter pylori-related gastrointestinal tract and brain disorders: A hypothesis.

The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies.

Helicobacter pylori infection as a potential risk factor for multiple sclerosis.

Helicobacter pylori infection (Hp-I) has been associated with a wide spectrum of gastrointestinal and extra-digestive manifestations, including neurodegenerative diseases. Contradictory data have been published on Hp-I and multiple sclerosis (MS) association, with studies mainly using serology for Hp-I detection that cannot distinguish between active and past infections. We herein hypothesize that humoral and cellular immune responses induced by active Hp-I, beyond damaging locally the gastric mucosa, they may shape the character of systemic autoimmune responses, contributing to MS pathogenesis. To investigate our hypothesis, active Hp-I has been diagnosed in two small MS Greek cohorts by using primarily gastric mucosa histology. A higher prevalence of active Hp-I was documented in MS patients vs. controls (86.4 vs. 50%, P = 0.002)accompanied by exclusive existence of duodenal ulcer and autoimmune diseases with endoscopic and histological findings of chronic active gastritis for the MS group. Our preliminary data suggested that active Hp-Iunlike other studies, may not protect, but contribute to MS and we proposed possibleHp-relating mechanisms involved in MS pathophysiology, that merit further evaluation.