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.

COVID-19 mRNA Vaccine Effectiveness against Elderly Frail People.

The frail, elderly population is often characterized by poor immunogenicity post COVID-19 mRNA vaccination. "Inflame-ageing" and "immune-senescence" are pathogenetic mechanisms that might explain this phenomenon. Complex interplay with cytokines and microbiota is also implicated in this inflammatory cascade. The abovementioned population, although very important from immunologic perspective, has barely been included in the mRNA vaccination clinical trials.

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.

Phylogenetic Analysis of Bird-Virulent West Nile Virus Strain, Greece.

We report the full polyprotein genomic sequence of a West Nile virus strain isolated from Eurasian magpies dying with neurologic signs in Greece. Our findings demonstrate the local genetic evolution of the West Nile virus strain responsible for a human disease outbreak in the country that began in 2010.

Serological and molecular investigation of selected parasitic pathogens in European brown hare (Lepus europaeus) in Greece: inferring the ecological niche of Toxoplasma gondii and Leishmania infantum in hares.

The occurrence of infection or exposure to Toxoplasma gondii, Neospora caninum, and Leishmania infantum was investigated in European brown hares (Lepus europaeus, EBH) hunter-harvested over two consecutive hunting seasons in northern and central Greece. Geographical information system was used along with the ecological niche model to define the geographical distribution of seropositive hares relative to environmental parameters and to identify high-risk areas for hare exposure. Molecular analysis showed that 3.8% and 9.6% of the examined hares were infected with N. caninum and L. infantum, respectively, while, 5.7%, 0.95%, and 12.4% of the hares tested positive for the presence of antibodies against T. gondii, N. caninum, and L. infantum respectively. None of the examined hares was polymerase chain reaction-positive for T. gondii. Mixed exposure against both T. gondii and L. infantum was found in 2.9% of the hares examined. Rainfall indices and land uses significantly influenced the exposure of hares to T. gondii and L. infantum. This is the first molecular and serological survey of protozoan pathogens in EBH in Greece. Furthermore, we report the environmental parameters related to hare seropositivity and present a risk map for hare exposure to T. gondii and L. infantum in northern and central Greece. The ecological niches of T. gondii and L. infantum in the hares presented herein could be applied to other regions with similar environmental and climatic conditions.

The Effect of Fatigue on Electromyographic Characteristics during Obstacle Crossing of Different Heights in Young Adults.

The aim of this study was to investigate the effect of fatigue on electromyographic (EMG) parameters of healthy young adults during obstacle crossing of two different heights. Twelve untrained male adults (23 ± 5 years of age) were fatigued running on a treadmill with increasing speed and inclination and walked over an obstacle with a height set at 10% and 20% of each individual's lower limb length. Maximal plantar flexor torque and EMG of the medial gastrocnemius, soleus, and tibialis anterior muscles of the trailing limb were assessed during obstacle crossing. Data were captured before, immediately after and 5 minutes after a fatigue session. Fatigue induced significant reduction on the plantar flexor torque output immediately after and 5 minutes after exhaustion. After fatigue gait speed was not affected, the minimum distance between the obstacle and the trailing or leading foot remained unchanged, and the trailing foot contacted the ground closer to the obstacle immediately after fatigue. Regarding the EMG, medial gastrocnemius became after fatigue more active during swing phase when increasing the obstacle height, whereas this was not the case before or 5 minutes after fatigue. No other significant difference was observed for any of the examined muscles. It is concluded that the assessed fatigue protocol induced only minimal changes in the EMG activity of the examined muscles during obstacle crossing. Therefore, it is suggested that the neuromuscular system of healthy young individuals is able to respond to the decreased force capacity after fatigue during obstacle crossing of heights up to the 20% of the limb length. Key PointsExhaustion after running on a treadmill induces significant reduction in plantar flexion strength and changes in the positioning of the feet relative to the obstacle during obstacle crossing.EMG activity of the calf muscles of the trailing limb does not change significantly after fatigue during the stance phaseDuring swing phase, medial gastrocnemius EMG activity of the trailing limb increases after fatigue when obstacle height increases.These minor changes in EMG after fatigue, reveals that untrained, healthy, young subjects may compensate the deficit in muscular force due to fatigue when performing obstacle crossing.

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.

Canonical NF-κB Promotes Lung Epithelial Cell Tumour Growth by Downregulating the Metastasis Suppressor CD82 and Enhancing Epithelial-to-Mesenchymal Cell Transition.

BACKGROUND: The development of non-small cell lung cancer (NSCLC) involves the progressive accumulation of genetic and epigenetic changes. These include somatic oncogenic KRAS and EGFR mutations and inactivating TP53 tumour suppressor mutations, leading to activation of canonical NF-κB. However, the mechanism(s) by which canonical NF-κB contributes to NSCLC is still under investigation. METHODS: Human NSCLC cells were used to knock-down RelA/p65 (RelA/p65KD) and investigate its impact on cell growth, and its mechanism of action by employing RNA-seq analysis, qPCR, immunoblotting, immunohistochemistry, immunofluorescence and functional assays. RESULTS: RelA/p65KD reduced the proliferation and tumour growth of human NSCLC cells grown in vivo as xenografts in immune-compromised mice. RNA-seq analysis identified canonical NF-κB targets mediating its tumour promoting function. RelA/p65KD resulted in the upregulation of the metastasis suppressor CD82/KAI1/TSPAN27 and downregulation of the proto-oncogene ROS1, and LGR6 involved in Wnt/ß-catenin signalling. Immunohistochemical and bioinformatics analysis of human NSCLC samples showed that CD82 loss correlated with malignancy. RelA/p65KD suppressed cell migration and epithelial-to-mesenchymal cell transition (EMT), mediated, in part, by CD82/KAI1, through integrin-mediated signalling involving the mitogenic ERK, Akt1 and Rac1 proteins. CONCLUSIONS: Canonical NF-κB signalling promotes NSCLC, in part, by downregulating the metastasis suppressor CD82/KAI1 which inhibits cell migration, EMT and tumour growth.

Investigation of the Role of the European Brown Hare in the Epidemiology of Bacterial Zoonotic Pathogens: A Serological and Molecular Survey in Greece.

The aim of this study was to investigate the occurrence of Bartonella spp, Brucella spp, Coxiella burnetii, and Francisella tularensis in European Brown hares (Lepus europaeus) hunter harvested during 2-year hunting periods in northern and central Greece. Serum samples were examined for the presence of IgG antibodies by using an immune fluorescence test and/or an enzyme-linked immunosorbent assay. PCR was used to detect Bartonella spp DNA in blood samples and Brucella spp, C. burnetii, and F. tularensis DNA in liver samples. Antibodies against Bartonella spp were detected in 12 hares (12/105); whereas none of the hares examined was seropositive for Brucella spp, C. burnetii, and F. tularensis. The presence of Bartonella spp, Brucella spp, C. burnetii, and F. tularensis DNA was not detected in the samples examined. This study did not provide any evidence that the European Brown hare is involved in the epidemiology of Brucella spp, C. burnetii, and F. tularensis in Greece. However, our results suggest that this species is exposed to Bartonella spp, which gives the impetus for further investigation of its role as another host of this bacterium.

Increased cerebrospinal fluid Helicobacter pylori antibody in Alzheimer's disease.

BACKGROUND: Helicobacter pylori (H. pylori) infection may play a role in Alzheimer's disease (AD). AIM: A prospective, nonrandomized, comparative study was car- ried out to examine the levels of anti-H. pylori-specific IgG antibodies in the cerebrospinal fluid (CSF) and serum of AD patients, compared with those of age-matched cognitively normal controls. PATIENTS: CSF was aspirated from 27 AD patients and 27 age-matched cognitively normal patients with prostate hyperplasia or long-bone fractures necessitating surgery after epidural anesthesia. Serum samples were obtained from AD patients and the day before surgery from controls. METHODS: CSF and serum anti-H. pylori IgG concentrations were measured by means of an enzyme-linked immunosorbent assay. RESULTS: The mean concentration of anti-H. pylori-specific IgG was significantly greater in (a) the CSF of AD patients (10.53 +/- 12.54 U/mL) than in controls (8.63 +/- 8.01 U/mL, p = 0.047), and (b) the serum of AD patients (30.44 +/- 33.94 U/mL) than in controls (16.24 +/- 5.77 U/mL, p = 0.041). CSF anti-H. pylori IgG antibodies correlated with the degree of severity of the disease. CONCLUSION: H. pylori-specific IgG antibody levels are significantly increased in CSF and serum of AD; its titer in CSF might reflect the AD severity, thereby supporting a role for this common infection in the pathobiology of the disease.

Yttrium-90 silicate radiosynovectomy treatment of painful synovitis in knee osteoarthritis. Results after 6 months.

Our aim was to evaluate the response of radiation synovectomy (RS) with yttrium-90 silicate ((90)Y-S) treatment of synovitis in patients with knee osteoarthritis (OA) and to derive factors that influence this response. The RS treatment response was assessed prospectively in 74 painful OA knees of 74 patients during a period of 6 months follow up. The duration of the disease was 24 +/- 9 months. Forty-four of the 74 knees had pain during the night and 43/74 had abnormal flexibility. Knee joints were graded according to the Steinbrocker radiological system. RS was performed according to the European Association of Nuclear Medicine guidelines. RS response was assessed considering the pain improvement from baseline values in terms of a 100-point visual analogue scale (VAS), the improvement of knee flexibility and the pain remission during the night. RS response was classified as poor (VAS<25), fair (VAS>or=25-50), good (VAS >or=50-75) and excellent (VAS>or=75), with excellent and good results considered as success, while fair and poor as failure. Our results show that 6 months after RS treatment, the percentage of VAS from baseline values was 66.0% +/- 24.8% and found to be significantly related to patients' age (P=0.01), duration of the disease (P=0.04) and to radiographic grading of OA (P=0.001). Knees without or with mineral type OA radiographic changes (Steinbrocker's grades 0-I) responded better than those with more advanced changes (Steinbrocker's grade III-IV) in terms of VAS improvement (77.9% versus 53.8%) (P < 0.001). The overall success rate (VAS >or= 50) was 83.8%. Remission of pain during the night was achieved in 88.6% and knee flexibility was improved in 65.1%. RS side effects assessed for the whole follow-up period were minor and not significant. In conclusion, RS with a single injection of (90)Y-S in patients with knee OA seems to have a significant therapeutic effect after a six months follow-up period with no significant side effects. Six months after RS treatment, clinical improvement was inversely related to radiographic knee damage, patients" age and duration of the disease. RS also induced remission of OA pain during the night.

Helicobacter pylori infection upregulates endothelial nitric oxide synthase expression and induces angiogenesis in gastric mucosa of dyspeptic patients.

BACKGROUND: Helicobacter pylori (H. pylori) infection induces nitric acid (NO) overproduction through inducible NO synthase (NOS) expression, subsequent DNA damage and enhanced antiapoptosis signal transduction sequence in the human gastric mucosa, whereas its possible effect on endothelial nitric oxide synthase (eNOS) expression has not as yet been investigated. The aim of this study was to evaluate the effect of H. pylori infection in the expression of eNOS in gastric mucosa. PATIENTS AND METHODS: We prospectively studied 30 nonsmoking dyspeptic patients (12 men, 18 women, mean age 54.26+/-12.89 years). The diagnosis of H. pylori infection was based mainly on histology. The histological grading of H. pylori infection was evaluated according to the modified Sydney classification. Histological grading of eNOS expression and microvessel density as estimated by CD34 expression were determined by immunohistochemistry (degree 0-3) and correlated with H. pylori infection and histological degree of gastritis. RESULTS: Twelve patients were H. pylori-positive and 18 patients were H. pylori-negative. The two groups were matched for age (P=0.139), sex (P=0.342) and similar degree of gastritis. Intensity of eNOS and CD34 expression in the corpus and antrum were significantly correlated (P<0.001). eNOS expression was correlated with H. pylori infection in the mucosa of the body and antrum (P=0.013 and 0.037, respectively) but not with gastric inflammation and activity (P=0.848 and 0.871, respectively, for the corpus and P=0.565 and 0.793, respectively, for the antrum). H. pylori-positive patients showed higher expression of CD34-positive blood vessels in the mucosa of the antrum (P=0.048). CD34 expression was correlated with gastric inflammation and activity (P=0.03 and 0.044, respectively) in the mucosa of the antrum of H. pylori-positive patients. CONCLUSION: H. pylori infection upregulates eNOS, and induces angiogenesis, contributing to H. pylori-associated pathophysiology in gastric mucosa.

Validity study of the Moral Judgment Test in Physical Education: development and preliminary validation.

Teaching ethical behavior is an aspect of physical education. The purpose of the study was to present the construction and to estimate validity of a test which assesses physical education students' moral judgment, the Moral Judgment Test in Physical Education. The sample comprised 281 male and female participants (95 in Grades 7 to 9, 92 in Grades 10 to 12, and 94 university students), who completed Lind's Moral Judgment Test and the Moral Judgment Test-PE version. The validity of the latter was assessed using four criteria of Lind's moral theory. Analysis indicated that the Moral Judgment Test-PE had adequate construct validity and correlated positively, although relatively weakly, with the original test, so the new version has sufficient construct validity to be used in physical education.