Search

Specifically, cognitively normal elderly persons with high A have hyperhomocysteinemia, thinner temporal lobe, and lesser daily memory.14 Our own results indicate that active I Hp i -I could be involved in the pathophysiology of mild cognitive impairment (MCI), a prodromal phase highly predictive of consequent AD development, via induction of chronic atrophic gastritis-hyperhomocysteinemia-AD sequence.15 Hyperhomocysteinemia seems to be an active player involved in the neuropathophysiology of MCI-AD sequence by inducing A and tau pathologies with synaptic dysfunction, neuroinflammation and memory deterioration, thereby suggesting a novel therapeutic option for the treatment of people bearing this risk factor.16 In this regard, beyond hyperhomocysteinemia, additional I Hp i -related MetS parameters contribute to MCI-AD sequence.4 Comparable data may also introduce in isolate clinical syndrome (CIS)-multiple sclerosis (MS) sequence.17,18 Our own data indicate that active I Hp i -I, beyond MS,17 is also frequent with CIS, the prodromal phase of consequent MS development, accompanied by hyperhomocysteinemia, and I Hp i eradication may delay CIS progression to MS development.18 Active I Hp i -I is also associated with primary open-angle glaucoma, which has been called "ocular AD" and pseudoexfoliative glaucoma in some populations studied.19,20 Moreover, I Hp i eradication seems to improve glaucoma parameters, thereby signifying a potential casual relation between I Hp i -I and glaucoma. Cardio-cerebrovascular disease and Helicobacter pylori -related metabolic syndrome: we consider eradication therapy as a potential cardio-cerebrovascular prevention strategy. [Extracted from the article]

A letter to the editor is presented in response to the article "The correlation of Helicobacter pylori with the development of cholelithiasis and cholecystitis: the results of a prospective clinical study in Saudi Arabia" by Guraya and colleagues in the previous issue.

A letter to the editor is presented in response to the article "Meta-Analysis: Barrett's Oesophagus and the Risk of Colonic Tumours," by J. Andrici, M. Tio, M.R. Cox, and G.D. Eslick in the 2013 issue.

Objective: The present study investigates the production of mebendazole nanocrystal formulations by wet media milling., Significance: Nanocrystal formulations are expected to enhance the dissolution properties of mebendazole, which possesses poor solubility, highly dependent on crystal polymorphism., Methods: A Box-Behnken design was employed to study the effects of formulation and process variables on the nanocrystal size and ζ-potential. The optimal nanosuspensions were solidified by spay-drying and freeze-drying with and without mannitol, and the effects of the drying method on the reconstitution of the nanosuspension was studied. Additionally, their physicochemical properties were determined, while the mechanism of fracture and stabilizer adsorption were investigated by atomistic simulations., Results: Poloxamer 407 is the most suitable stabilizer, while the bead size, milling speed, and stabilizer content significantly affect the diameter. The ζ-potential is affected by the stabilizer concentration depending on bead size. Energy-vector diagrams revealed a slip plane in the lattice of form C, while molecular dynamics simulations revealed strong interactions between stabilizer and crystal surface. Both drying processes induce polymorphic transformation to form A, which, however, can be partially prevented by the addition of mannitol in freeze-drying, at the expense of suspension redispersibility. The spray-dried nanosuspensions exhibited substantially enhanced dissolution profile compared to neat mebendazole, probably due to reduction of particle size, despite transformation to the unfavorable form A., Conclusions: Nanocrystal formulations exhibited significant dissolution enhancement, while experimental design and atomistic simulations provided useful insights into the mechanism of their formation and stability.

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.)

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) 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.

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.)

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.