This paper numerically investigates a 3D mesh independency study of a straight blade horizontal axis tidal turbine modelled using Computational Fluid Dynamics (CFD). The solution was produced by employing two turbulence models, the standard k-ε model and Shear Stress Transport (SST) in ANSYS CFX. Three parameters were investigated: mesh resolution, turbulence model, and power coefficient in the initial CFD, analysis. It was found that the mesh resolution and the turbulence model affect the power coefficient results. The power coefficients obtained from the standard k-ε model are 15% to 20% lower than the accuracy of the SST model. It can also be demonstrated that the torque coefficient increases with the increasing Tip Speed Ratio (TSR), but drops drastically after TSR = 5 and k-ε model failing to capture the non-linearity in the torque coefficient with the increasing TSR.

Optimizing the NACA0015 airfoil which is widely applied in small-scale vertical axis wind turbine to make it has a better aerodynamic performance. In the optimization process, using CST parameterization method to perturb the airfoil geometry, the thickness and camber of the airfoil are selected as the constraint, and the value of the maximum tangential force coefficient is chosen as the objective function, the genetic algorithm based on non-dominated sorting (NSGA-II)is selected as an optimization method, calculates the aerodynamic performance of the airfoil by applying the approach of combining XFOIL program and Viterna-Corrigan post-stall mode ,and establishes the optimizing process by the optimization software modefrontier for NACA0015 airfoil’s muti-point optimization, validate the airfoil’s performance with CFD finally. The result illustrates that, by comparing with the NACA0015 airfoil, the optimized airfoil’s lift to drag ratio is improved over a wide range of attack angles, the stall performance is more gentle. The maximum lift coefficient, the maximum lift-drag ratio and the maximum tangential force coefficient are increased by 7.5%,9 and 8.87%, respectively. The optimized airfoil has a wide variable condition performance, more suitable for the operating conditions of a vertical axis wind turbine. Finally, predict the rotor efficiency with optimized airfoil and NACA0015 airfoil for different tip speed ratios and different solidities with multiple streamtube model, the result shows the rotor with optimized airfoil has a higher efficiency.

Liver cirrhosis is a chronic disease that is characterized by the presence of fibrosis and regeneration of nodules in the liver whose consequences are the development of portal hypertension and liver failure. Cirrhosis arises from a wide variety of chronic diseases, which progresses slowly after years or decades. Liver cirrhosis is a public health problem. It is usually associated with viral hepatitis, consumption of alcohol, metabolic syndrome, autoimmune processes, storage diseases, toxic substances, and medications. Cirrhosis is the fourteenth most common cause of death in adults throughout the world, the fourth in Europe and the ninth in the United States. The prevalence of this disease is underestimated because it is symptomatic it is not diagnosed in initial stages, and it usually goes to the decompensated stage at a rate of 5 to 7% per year. We review here the epidemiology, pathophysiology, etiology, and diagnosis of liver cirrhosis.

Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and its co-morbidities, like fatty liver disease, insulin resistance/diabetes and cardiovascular events. Among several factors, dietary patterns, probiotics, prebiotics, synbiotics, antimicrobials and non-dietary factors, such as stress, age, exercise and climatic conditions, can dramatically impact the human gut microbiota diversity and equilibrium. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.

Fructose consumption has been growing exponentially and, concomitant with this, the increase in the incidence of obesity and associated complications has followed the same behavior. Studies indicate that fructose may be a carbohydrate with greater obesogenic potential than other sugars. In this context, the liver seems to be a key organ for understanding the deleterious health effects promoted by fructose consumption. Fructose promotes complications in glucose metabolism, accumulation of triacylglycerol in the hepatocytes and alterations in the lipid profile, which, associated with an inflammatory response and alterations in the redox state, will imply a systemic picture of insulin resistance. However, physical exercise has been indicated for the treatment of several chronic diseases. In this review, we show how each exercise protocol (aerobic, strength or a combination of both) promote improvements in the obesogenic state created by fructose consumption as an improvement in the serum and liver lipid profile (HDL increase and decrease TG and LDL levels) and a reduction of markers of inflammation caused by an excess of fructose. Therefore, it is concluded that the practice of aerobic physical exercise, strength or a combination of both is essential for attenuating the complications developed by the consumption of fructose.

A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans. This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription–PCR (RT–qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly higher in AFB1 positive samples compared to control AFB1-negative. AFB1 was positively correlated with AST and ALT as liver function enzymes and with age as a risk factor of long duration of AFB1 chronic exposure. Multiple linear regression analysis ascertained the association between AFB1 chronic exposure and ALT increase in liver dysfunction Saudi patients. Conclusion: Measurement of elevated ALT as marker of liver injury in AFB1 chronically exposed Saudi patients can help to avoid the future development of HCC. Moreover, early detection of AFB1 exposure, together with early vaccination against HBV and HCV can remove the synergistic effects of these two etiological factors and thus decrease the risk of developing liver cancer.

In this study, we investigated the effects of Akebia quinata ethanol extract (AE), Akebia quinata sikhye (AS), and Akebia quinata water extract (AW) on alcohol-induced liver injury in rats. The hepatoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects of AE, AS, and AW were examined. Experimental animals were randomly divided into five groups: normal, ethanol, AE (10 mL/kg), AS (10 mL/kg), and AW (10 mL/kg). Each group was administered the respective treatment orally once per day for 21 days. CYP2E1 mRNA expression was significantly lower in the AE, AS, and AW groups than that in the ethanol group. Pro-inflammatory cytokines including cyclooxygenase-2, IL-6, and TNF-α increased significantly in the ethanol group but these increases were ameliorated with AE, AS, and AW treatment. Moreover, the expression of the apoptosis-associated proteins Bax, p53, procaspase-3, and PARP decreased after treatment with AE, AS, and AW. The expression of antioxidant enzymes including BCL-2, SOD, and GST slightly decreased in the ethanol group, but AE, AS, and AW treatment augmented their activities. AQ extracts and AS attenuated ethanol-induced increases in the levels of phosphorylated p-AKT, p-ERK, and p-JNK. These results demonstrate that AQ is a competence indicator for inhibiting alcoholic liver injury.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

The global energy crisis has lead researchers explore other sources of energy like wind, resulting in a wide acceptance of wind turbines. Vertical axis wind turbines (VAWT) more suitable for small scale application in urban conditions than their horizontal-axis counterparts. A Helical bladed VAWT would reduce the ripple effect when compared to Straight bladed VAWT. The effect of the blade helix angle on the aerodynamic performance of VAWT using 3D numerical simulations is studied. Turbulence modelled using 4-Equation transition SST k-w model. Three different helix angles of 60, 90 and 120 of a 3 bladed VAWT operating across different tip speed ratios were studied. The 60 helical bladed VAWT was found to perform better than all other helical bladed and straight bladed VAWT. Standard deviation of the moment coefficient generated by a blade plotted against 360 of azimuth rotation revealed that the ripple effect on the shaft produced by cyclic loading of the straight blade is considerably reduced upon introduction of helix angle, with 120 helical blade giving lowest standard deviation. The analysis has been done for the percentage of power generated by each quartile of flow and the contribution of each section of the blade. A comparative study was also conducted between different helical bladed VAWT and straight bladed VAWT. Flow feature analysis also revealed the reasons behind secondary peaks and the performance improvement when tip speed ratio increases. Wake structure analysis and flow contours were also studied for a better understanding of the flow field.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

The specific role of nicotinamide adenine dinucleotide (NAD) in hepatic triglyceride (TG) accumulation in alcoholic fatty liver disease (AFLD) were unclear. Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of AFLD is still elusive. In current investigation, we found that chronic alcohol exposure enhanced hepatic PARP expression and activity and lowered hepatic NAD⁺ level. PARP activity inhibitor PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD⁺ level in hepatocyte. These mechanistic observation was validated in alcohol-fed mice injected with PJ34 intraperitoneally. PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Further, the gene expression of hepatic SERBP-1c, DGAT1 and DGAT2 were lowered by PJ34 injection, while the hepatic NAD⁺ level was augmented by PJ34 injection in alcohol-fed mice. At last, the nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD⁺ depletion and TG accumulation in alcohol-fed mice, which might be a potential candidate for AFLD therapy.

Tidal stream energy is a low carbon energy source. Tidal stream turbines operate in a turbulent environment, and the effect of the structure between the turbine and seabed on this environment is not fully understood. An experimental study using 1:72 scale models based on a commercial turbine design was carried out to study the support structure influence on turbulence intensity around turbine blades. The study was conducted using the wave-current tank at LABIMA, University of Florence. A realistic flow environment (ambient turbulent intensity = 11%) was established. Turbulence intensity was measured upstream and downstream of a turbine mounted on two different support structures (one resembling a commercial design, the other the same with an additional vertical element), in order to quantify any variation in turbulence and performance between the support structures. Turbine drive power was used to calculate power generation. Acoustic Doppler Velocimetry was used to record and calculate upstream and downstream turbulence intensity. In otherwise identical conditions, performance variation of only 4% was observed between two support structures. Turbulent intensity at 1, 3 and 5 blade diameters, both upstream and downstream, showed variation up to 21% between the two cases. The additional turbulent structures generated by the additional element of the second support structure appears to cause this effect, and the upstream propagation of turbulent intensity is believed to be permitted by surface waves. This result is significant for the prediction of turbine array performance.

Plants and plant-derived food products have been used for medicinal purposes since the ancient. Medicinal Plant-based functional foods or plant-based dietary compounds are a re-emerged interest for their therapeutic benefits and nutritive supports which has implicated in healthcare systems across the world. Neurological disorders are one of the greatest threats to public health and according to the World Health Organization, about 100 million people are affected globally by several neurological and mental ailments. In a traditional medication system, medicinal plants have been applied as both neuro-therapeutic purposes and micro-macro nutrients provider for the wellbeing of psychological states e.g. anti-depressant, anti-anxiety, anti-convulsions, anti-dementia, anti-psychotic, etc. Herein, it is a topic of great interest to present a conceptual aspect by reviewing relevant scientific literature about the plant-based functional foods or bioactive phytochemicals for the prevention and treatment of mental and neurological disorders. From the literature assessment, we have found that nutritional neuroscience is becoming an advanced research discipline and there has been a growing pile of evidence concerning the therapeutic use of plant-based functional foods and/or plant-derived food compounds for the management of neurologic health, evolving with promising impact over the time.

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

The modification the gut microbiota in metabolic syndrome and associated chronic diseases is among leading tasks of microbiome research and needs for clinical use of probiotics. Evidence lack for the implications for microbiome modification to improve metabolic health in particular when applied impersonalized. Probiotics have tremendous potential in personalized nutrition and medicine to develop healthy diets. The aim was to to conduct comprehensive overview of recent updates of role of microbiota on human health and development of metabolic syndrome and efficacy of microbiota modulation considering specific properties of probiotic strain and particular aspects of metabolic syndrome and patient`s phenotype to fill the gap between probiotic product and individual to facilitate development of individualized / personalized probiotic and prebiotic treatments. We discuss the relevance of using host phenotype-associated biomarkers, those based on imaging and molecular and patrient`s history, reliable and accessible to facilitate person-specific appication of probiotics and prebiotic substances. Microbiome phenotypes can be parameters of predictive medicine to recognize patient`s predispositions and evaluate treatment responses; the number of phenotype markers can be effectively involved to monitor microbiome modulation. The studied strain-dependent properties of probiotic strains are potentially relevant for individualized treatment for gut and distant sites microbiome modulation. The evidence regarding probiotic strains properties can be taken to account via pathophysiology-based approach for most effective individualized treatment via gut, oral and vaginal and other sites microbiome modulation according to phenotype of the patient providing individualized and personalized medical approaches. Preventive potential of probiotics is strong and well-documented. Recommendations for individualized clinical use of probiotics, and for probiotic studies design have been suggested.

According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Psoriasis is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn’s disease, allergy, obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease as well as gives immune system role in the given condition. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting role of bacteria in the chronic disease and future studies in this field.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. The levels/ activity in various models reviewed are also included. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Biological nitrogen (N) provisioning is a seminal function of the gut microbes in several terrestrial insects, given the unbalanced carbon (C) and N ratios of their diets. Although freshwater insects face comparable dietary N limitations like terrestrial insects, little is known about this function by their gut microbiomes. In this study, we investigated microbial nitrate reduction to ammonium pathways as possible routes of biological N provisioning in two freshwater insects; filter-feeding Hydropsychidae and grazers/collectors Baetidae. After incubation in filtered (microbe-free) artificial stream water (ASW) containing dissolved ¹⁵N-labeled nitrate (treatment) or standard nitrate (control), bulk δ¹⁵N values of treatment samples (Baetidae = 100.62 ± 10.23, mean ± S.E.; Hydropsychidae = 76.82 ± 7.20) were significantly higher than controls (Baetidae = 10.14 ± 0.12 ; Hydropsychidae = 9.03 ± 0.20) in both functional feeding groups (F _{(3, 13)} = 296, P < 0.0001). The treatment δ¹⁵N values are cautiously interpreted as reflecting uptake and incorporation of microbe-derived ¹⁵N-metabolites (¹⁵NH₄ or ¹⁵N-amino acids) into host tissues following nitrate reduction to ammonium pathways in the gut lumen. Microbial nitrate reduction to ammonium activities was assessed via the quantification of dissimilatory (nrfA) and assimilatory (nasA) nitrate reduction to ammonium gene transcripts. There were no significant differences between control and treatment groups within each insect groups. Overall, this study provides a demonstration of the feasibility of applying ¹⁵N-stable isotope analysis for investigating, potential symbiotic functions of freshwater insect gut microbiomes, despite the preliminary nature of the results.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Background: Gut-Brain-Axis provides bidirectional communicational route; imbalance of which can have pathophysiological consequences. It is a frontier in autism research, affects 85% of autistic children (NIH report). Their microbiome has few overall microbes and smaller number of health promising microbes than their neurotypical peers. We hypothesize autism gut might play a role in manifestation of autism behaviours and on treatment, can revert back to normal behaviour considerably. The aim is to better understand to what degree gut microbiota of autism subjects differs from controls and identify bacterial species present exclusively in autism. Materials and Methods: 16s-rRNA-sequence of autism-subjects were retrieved from the American Gut Project Archive. Taxonomic assignment was inferred by similarity based methods using Quantitative Insights Into Microbial Ecology (QIIME). Species abundance was characterized and co-occurrence network was built to infer species interaction using measures of diversity. Statistical parameters were considered to validate the findings. Result: A total of 206 (1.8%) of American Gut Project datasets onstituted of autistic samples. Various bacteria such as Akkermansia sp., and Prevotella sp., were harboured in higher abundance in autistic children with statistical significance than in controls. Conclusion: These findings indicate connecting-link between gut-microbiome-brain-axis and autistic behaviour which can result in improved management

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×10⁶ CFU/g B. coagulans), B7 group (basal diet + 2×10⁷ CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H₂O₂ in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b^0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database γ-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

Recently scientific research began to shift their focus on looking at both the gut and the skin microbiota as having a reciprocal and integral relationship with one another, rather than assessing them as separate and unrelated fields. In the past five years, the field of microbial endocrinology emerged, which examines how our gut microbiota influences and modulates hormones. We’ve known for decades that hormones greatly affect the condition of the skin, and many skin conditions are often treated with oral hormonal therapy as means to internally treat skin conditions visible on the dermis. Now, a growing body research and discourse examining this triad of biological spheres – gut microbiota, skin microbiota, and the endocrine system – as interconnected rather than binary and unrelated. While there is ample research established and being conducted examining the gut-skin axis, the gut-brain axis, and the gut-hormone axis, through this paper I will review and synthesize some of the significant advancements in this emerging and inclusive field of science to suggest that the fields need to expand the axis and their modality for researching these fields as a connected whole in order to better understand the role of the microbiota in disease prevention as a whole.

The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion (“post-exertional malaise”) and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is largely comprised of disturbances to immunological and inflammatory pathways, autonomic and neurologic systems, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiome disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a far-reaching homeostatic shift affecting each of these systems. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a novel paradigm about a novel role of NGFs: NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to pertinent and imperative behavioural effects. NGFs are known to play crucial role in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important function in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been reported. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the biology of psychiatric disorders and may open ways for new therapeutic approaches.

The mammalian gut ecosystem plays critical roles in multiple functions related to health and homeostasis. In many cases, disturbances in the gut ecosystem are associated with a large number of metabolic and chronic diseases and disorders such as diabetes, cancer, and obesity. A diverse community of microorganisms ranging from viruses to bacteria comprise the gut microbiota, which is often considered as an organ in itself. Recent studies have profiled the influence of lifestyles and dietary behavior by comparing the gut microbiome of populations with different cultural underpinnings. In this review, we provide an overview of the studies which report the influence on the gut microbial composition of dietary and lifestyle patterns in different contexts such as western industrialized countries and indigenous cultures (corresponding to different lifestyle gradients such as hunter-gatherers and pastoralists) and how this association may influence health and disease.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.

The clinical characterization of small hepatocellular carcinoma (HCC) lesions in the liver and differentiation from heterogeneous inflammatory or fibrotic background is important for early detection and treatment. Metabolic monitoring of hyperpolarized ¹³C-labeled substrates has been suggested as a new avenue for diagnostic magnetic resonance. The metabolism of hyperpolarized [1-¹³C]pyruvate was monitored in mouse precision-cut liver slices (PCLS) of aged MDR2-KO mice, which served as a model for heterogeneous liver and HCC that develops similarly to the human disease. The relative in-cell activities of lactate dehydrogenase (LDH) to alanine transaminase (ALT) were found to be 0.40 ± 0.06 (n = 3) in healthy livers (from healthy mice), 0.90 ± 0.27 (n = 3) in heterogeneously inflamed liver, and 1.84 ± 0.46 (n = 3) in HCC. Thus, the in-cell LDH/ALT activities ratio was found to correlate with the progression of the disease. The results suggest that the LDH/ALT activities ratio may be useful in the assessment of liver disease. Because the technology used here is translational to both small liver samples that may be obtained from image-guided biopsy (i.e., ex vivo investigation) and to the intact liver (i.e., in a non-invasive MRI scan), these results may provide a path for differentiating heterogeneous liver from HCC in human subjects.

Citrullinemia is the earliest identifiable biochemical abnormality in neonates with intrahepatic cholestasis due to a citrin deficiency (NICCD) and it has been included in newborn screening panels using tandem mass spectrometry. However, only one neonate was positive among 600,000 infants born in Sapporo city and Hokkaido, Japan between 2006 and 2017. We investigated 12 neonates with NICCD who were initially considered normal in newborn mass screening (NBS) by tandem mass spectrometry, but were later diagnosed with NICCD by DNA tests. Using their initial NBS data, we examined citrulline concentrations and ratios of citrulline to total amino acids. Although their citrulline values exceeded the mean of the normal neonates and 80 % of them surpassed +3SD, all were below the cutoff of 40 nmol/mL. The ratios of citrulline to total amino acids significantly elevated in patients with NICCD compared to the control. By evaluating two indicators simultaneously, we could select about 80% of patients with missed NICCD. Introducing an estimated index comprising citrulline values and citrulline to total amino acid ratios could assure NICCD detection by NBS.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

Abstract: Role of gut microbiome in human health is becoming apparent. The major functional impact of gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or get absorbed in the circulation to impact distant cells/organs. Short chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through fermentation of non-digestible fibers. SCFAs are known to function through various mechanism, however, their signaling through free-fatty acid receptor 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is new therapeutic approach. FFAR2/3 are widely expression in diverse cell types in human and mice, and functions as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulates neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response and hormone synthesis. FFAR2/3 functions through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discussed the wide-spread expression and structural homologies between human and mice FFAR2/3, and their role in different human health conditions. This information can unlock opportunities to weigh the potential of FFAR2/3 as drug target to prevent human diseases.

Abstract: Supplementation of infant formula with ingredients potentially able to manage, in a way positive for the host, the gut microbiota of infants, is nowadays widely used by infant food producers. The impact of this class of compounds, named prebiotics, on gut microbiota composition, was initially measured on the enrichment of Bifidobacterium and Lactobacillus spp., but the use of culture-independent analytical techniques has allowed to establish that a larger number of intestinal microorganisms are affected by the ingestion of prebiotics. However, despite a relevant number of scientific publications, actually there is no consensus on the amount of prebiotics to be administered daily, the potentially different actions exerted by prebiotics which differ in biochemical structures, as well as the impact of different percentages of the same prebiotics when used in mixtures and/or combination. This paper is aimed to critically review the available data on the use of prebiotics in infant formula, with special attention paid to identify a link between, the dosage used, the mixture composition and the observed outcomes, keeping in mind the influences in nutrition quality and growth influence.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research venues focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish model candidates and their key potential for advancing research fields linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish, sticklebacks, guppies and cleaner-client dyads, will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

Introduction: Liver cirrhosis develops in about 10% of alcohol abusers. To date, a number of cells and cytokines have been identified, which are involved in induction of liver fibrotic processes. Nevertheless, the pathogenesis of liver cirrhosis has not been fully elucidated. The aim of the present study was to determine serum concentrations of afamin and adropin in patients with alcoholic liver cirrhosis and to define their correlation with the stage of disease. Materials and methods: The study included 99 patients with alcoholic cirrhosis from the region of Lublin, (Eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests and abdominal ultrasonography. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The serum afamin and adropin concentrations were determined using ELISA kits. Results: The concentration of afamin was found to be significantly lower in patients with compensated alcoholic liver cirrhosis, i.e. P-Ch B (85.1±40.6 μg/ml) and P-Ch C (56.4±32.3 μg/ml) individuals, as compared to the control group (135.9±43.6 μg/ml); p-value was <0.01 and <0.001, respectively. As far as adropin is concerned, a reverse relationship was demonstrated: the highest concentration was found in patients with P-Ch C (11.7±5.7 ng/ml) cirrhosis. Furthermore, the above concentration was significantly higher compared to patients with P-Ch A cirrhosis (7.2±2.8 ng/ml; p<0.05) and controls (7.5±2.6 ng/ml; p<0.05). Conclusions: The concentration of afamin decreases with the severity of alcoholic liver cirrhosis, which most likely results from impaired hepatic synthesis. Otherwise, the higher the stage of disease according to the Child-Pugh score, the higher the concentration of adropin.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

Spondyloarthritis comprises of a group of inflammatory diseases of the joints and spine with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

The microbiome gut brain (MGB) axis involves bidirectional routes of communication and has emerged as a potential therapeutic target for multiple medical specialities including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. The link between the gut microbiome and irritable bowel syndrome (IBS) is well established. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced clinically measurable symptom improvement in patients with depressive disorder. To date some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) with hepatocytes targeting as carriers for the magnetic resonance imaging (MRI) contrast agent (i.e., magnetic nanostructured lipid carriers, MNLCs), and to evaluate the targeting ability of the MNLCs with T2-weighted MRI both in vitro and in vivo. Here, the galactose-octadecylamine (Gal-ODA) conjugates were synthesized by chemical coupling reaction between lactose acid (LA) and octadecylamine (ODA). Then the superparamagnetic iron oxide (SPIO) loaded nanostructured lipid carrier (conjugated by Gal-ODA, Gal-NLC-SPIO) was prepared by emulsification-ultrasonic method using monoglyceride as lipid materials. The Gal-NLC-SPIO with a diameter of about 50 nm could specifically internalize into LO2 (human hepatic cell line) cells. In vitro MRI results also proved the specific targeting ability of Gal-NLC-SPIO to LO2 cells. The in vivo MR imaging experiments using an orthotopic intrahepatic xenograft tumor model further validated the hepatocytes targeted effect of Gal-NLC-SPIO. The results of this study suggested that Gal-NLC-SPIO can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Background: Medicinal plants are of great importance to health of individual and communities. About 80% of the population in Uganda relies on traditional medicine because western-trained medical personnel are limited especially in villages. Most Ugandans use Hymenoxys odorato for medicinal purposes e.g. to treat colds, fever, coughs, anti-helminthes, locally used as tea, anti-allergy and also as an anti-venom to relieve snake bites. Method: A group of 25 male wistar rats of 150 g–210 g were kept for 14 days while being fed and treated with the extract. At 14^th day, anesthesia was given and blood samples collected by cardiac puncture for hematological and biochemical investigations. Serum was analyzed for Alkaline Phosphatase, Aspartate Transaminase and Alanine Transaminase while whole blood was used for complete blood count. The liver and kidney were removed and placed in 10% formalin to prepare for histology staining using haematoxylin and eosin technique. Results: The extract elevated hepatic biomarker enzymes i.e. ALP, ALT and AST. The increase was found to be significantly different (P > 0.05) at 400 and 500 mg/kg doses as compared to the control group. Histological sections of the liver showed distortion of liver cytoarchitecture, steatosis, necrosis of hepatocytes and congestion of the sinusoids at high doses 300, 400 and 500 mg/kg body weight. In the sections of the kidney, there was mild distortion of the integrity of the kidney with glomerular hypercellularity at high doses (400 and 500 mg/kg per body weight). Conclusion: Hymenoxys odorato aqueous extract has toxic effects on the liver and kidney of wistar rats. The effects were observed to be in a dose dependent manner.

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

In this paper, we define Ulisse Dini-type helicoidal hypersurface with spacelike axis in Minkowski 4-space ${\mathbb{E}}_1^4$ . We compute the Gaussian and the mean curvature of the hypersurface. Moreover, we obtain some special symmetry to the curvatures when they are flat and maximal.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

In the Korean construction industry, legal and institutional safety management improvements are continually being pursued. However, there was a 4.5% increase in the number of workers’ deaths at construction sites in 2017 compared to the previous year. Failure to wear safety helmets seems to be one of the major causes of the increase in accidents, and so it is necessary to develop technology to monitor whether or not safety helmets are being used. However, the approaches employed in existing technical studies on this issue have mainly involved the use of chinstrap sensors and have been limited to the problem of whether or not safety helmets are being worn. Meanwhile, improper wearing, such as when the chinstrap and harness fixing of the safety helmet are not properly tightened, has not been monitored. To remedy this shortcoming, a sensing safety helmet with a three-axis accelerometer sensor attached was developed in this study. Experiments were performed in which the sensing data were classified whether the safety helmet was being worn properly, not worn, or worn improperly during construction workers’ activities. The results verified that it is possible to differentiate among wearing status of the proposed safety helmet with a high accuracy of 97.0%

A modified free-wake vortex ring model is proposed to compute the dynamics of a floating horizontal-axis wind turbine. The model is divided into two parts. The near wake model uses a blade bound vortex model and trailed vortex model, which is developed based on vortex filament method. By contrast, the far wake model is based on the vortex ring method. The proposed model is a good compromise between accuracy and computational cost, for example when compared with more complex vortex methods. The present model is used to assess the influence of floating platform motions on the performance of a horizontal-axis wind turbine rotor. The results are validated on the 5MW NREL rotor and compared with other aerodynamic models for the same rotor subjected to different platform motions. It was found that the results from the proposed method are more reliable than the results from BEM theory especially at small angles of attack in the region of low wind speeds, on the one hand, and high wind speeds with blade pitch motions, on the other hand. And also the proposed method is less time consuming and has similar accuracy when comparing with more advanced vortex based methods.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. In this review, we review evidence showing the advantages of the spleen as a transplantation site for islets. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets and that splenic stem cells have the potential to differentiate into islet cells. The spleen also has some disadvantages associated with the transplantation procedure itself (bleeding, thrombosis and splenic infarction). The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic to support the engraftment of multiple transplanted islets.

The tissue micro environment or milieu consists of a highly dynamic population of cellular and non-cellular components which constitute a complex regulatory network aimed at maintaining the organ homeostasis. In the modern medicine the discovery of miRNAs is undoubtedly a promising field of research and they are essential in orchestrating immune system logic and their release in the gut micro milieu can directly affect bacterial gene expression. Here, we briefly review the role of microRNAs, focuses on their role on immune system components in physiological and pathophysiological gut micro milieu.

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.

Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC.

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to end-stage of hepatocellular carcinoma and demolition of hepatic structures. EMT has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing complementary sequence of Smad transcription factor. Thus, this study evaluated the anti-fibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice. As shown in histological results, CCl₄ treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN treatment mice compared with CCl₄-injuried mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

This paper discusses the computer-aided (CAD) classification between Hepatocellular Carcinoma (HCC), i.e., the most common type of liver cancer, and Liver Abscess, based on ultrasound image texture features and Support Vector Machine (SVM) classifier. Among 79 cases of liver diseases, with 44 cases of HCC and 35 cases of liver abscess, this research extracts 96 features of Gray-Level Co-occurrence Matrix (GLCM) and Gray-Level Run-Length Matrix (GLRLM) from the region of interests (ROIs) in ultrasound images. Three feature selection models, i) Sequential Forward Selection, ii) Sequential Backward Selection, and iii) F-score, are adopted to determine the identification of these liver diseases. Finally, the developed system can classify HCC and liver abscess by SVM with the accuracy of 88.875%. The proposed methods can provide diagnostic assistance while distinguishing two kinds of liver diseases by using a CAD system.

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

In 2001, the first author of this paper reported that schizophrenia is associated with an increased frequency of the haptoglobin (Hp)-2 gene. The precursor of Hp-2 is zonulin, a molecule that affects intercellular tight junction integrity. Recently, we reported increased plasma IgA/IgM responses to Gram-negative bacteria in deficit schizophrenia indicating leaky gut and gut dysbiosis. The current study was performed to examine the integrity of the paracellular (tight and adherens junctions) and transcellular (cytoskeletal proteins) pathways in deficit versus non-deficit schizophrenia. We measured IgM responses to zonulin, occludin, E-cadherin, talin, actin and vinculin in association with IgA responses to Gram-negative bacteria, CCL-11, IgA responses to tryptophan catabolites (TRYCATs), immune activation and IgM to malondialdehyde (MDA) and NO-cysteinyl in 78 schizophrenia patients and 40 controls. We found that the ratio of IgM to zonulin + occudin / talin + actin + viculin (PARA/TRANS) was significantly greater in deficit than in non-deficit schizophrenia and higher in schizophrenia than controls and was significantly associated with increased IgA responses to Gram-negative bacteria. IgM responses to zonulin were positively associated with schizophrenia (versus controls), while IgM to occludin was significantly associated with deficit schizophrenia (versus non-deficit schizophrenia and controls). A large part of the variance (90.8%) in negative and PHEM (psychosis, hostility, excitation and mannerism) symptoms was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, IgM to E-cadherin and malondialdehyde (MDA) and memory dysfunctions, while 53.3% of the variance in the latter was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, CCL-11, TRYCATs and immune activation. The results show an upregulated paracellular pathway with breakdown of the tight and ahherens junctions and increased bacterial translocation in deficit schizophrenia. These dysfunctions in the intestinal paracellular route together with lowered natural IgM, immune activation and production of CCL-11 and TRYCATs contribute to the phenomenology of deficit schizophrenia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. The clinical symptoms of the disease vary from mild illness to acute respiratory issues. Older age, diabetes, cardiac diseases predict poor prognosis in COVID-19 patients. Various reports mention the incidence of liver injury with transient elevations in the levels of aminotransferases (liver function enzymes). The clinical characteristics, etiology and underlying pathophysiological mechanisms associated with liver damage in SARS-CoV2 infected patients need to be explored. This review highlights the severity of the hepatic injury in COVID-19.

The basic equation for estimating the aerodynamic power captured by an Anderson Vertical Axis Wind Turbine (AVAWT) is a solution of the Navier-Stokes(N-S) equations for a baroclinic, inviscid flow. In a nutshell, the pressure difference across the AVAWT is derived from Bernoulli’s equation; an upshot of the integration of the N-S momentum equation for a baroclinic inviscid flow, Euler’s momentum equation. The resulting expression for the pressure difference across the AVAWT rotor is plotted as a function of freestream speed. Experimentally determined airstream speeds at the AVAWT inlet and outlet, coupled with corresponding freestream speeds are used in estimating the aerodynamic power captured. The aerodynamic power is subsequently used in calculating the aerodynamic power coefficient of the AVAWT. The actual power coefficient is calculated from the power generated by the AVAWT at various free stream speeds and plotted as a function of the latter. Experimental results show that, at all free stream speeds and tip speed ratios, the aerodynamic power coefficient is higher than the actual power coefficient of the AVAWT. Consequently, the power generated by the AVAWT prototype is lower than the aerodynamic power captured, given the same inflow wind condition.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Abstract: Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome and diet influence the diversity, abundance and function of the early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD) and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during the early life stage. In fact, it is critical to explore the role of the human gut microbiota in early life. In this review, we summarize the general understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the relationship between the gut microbiota composition and their metabolites, and immune functions, which could significantly influence long-term health and disease. We then review known pathophysiological interactions of the early gut microbiome with a number of well characterized diseases and pose potential etiological mechanisms.

Objective: Several lines of evidence support a relationship between circadian rhythms disruption in the onset, course, and maintenance of mental disorders. Despite the study of circadian phenotypes promising a decent understanding of the pathophysiologic or etiologic mechanisms of psychiatric entities, several questions still need to be addressed. In this review, we aimed to synthesize the literature investigating chronobiologic theories and their associations with psychiatric entities. Methods: The Medline, Embase, PsycInfo, and Scopus databases were comprehensively and systematically searched and articles published between January 1990 and October 2019 were reviewed. Different combinations of the relevant keywords were polled. We first introduced molecular elements and mechanisms of the circadian system to promote a better understanding of the chronobiologic implications of mental disorders. Then, we comprehensively and systematically reviewed circadian system studies in mood disorders, schizophrenia, and anxiety disorders. Results: Although subject characteristics and study designs vary across studies, current research has demonstrated that circadian pathologies, including genetic and neurohumoral alterations, represent the neural substrates of the pathophysiology of many psychiatric disorders. Impaired HPA-axis function-related glucocorticoid rhythm and disrupted melatonin homeostasis have been prominently demonstrated in schizophrenia and other psychotic disorders, while alterations of molecular expressions of circadian rhythm genes including CLOCK, PER, and CRY have been reported to be involved in the pathogenesis of mood disorders. Discussion: Further translational work is needed to identify the causal relationship between circadian physiology abnormalities and mental disorders and related psychopathology, and to develop sound pharmacologic interventions.

Inflammatory bowel diseases, familial adenomatous polyposis (FAP) and colorectal cancer (CRC) are associated with alterations of the intestinal microbiota. However, few data are available on the perpetuation of FAP and ulcerative colitis (UC) in relation to microbial dysbiosis. This study evaluated the UC and genetically confirmed FAP patients’ gut microbial balance in concordance to clinical outcome. Fecal materials (average mass of 0.54 g) were collected from three FAP and five UC patients to compare with healthy individuals as control group. Genomic materials of micro-biota were isolated for next generation sequencing of 16S rRNA that was performed by using QIAseq 16S/ITS panel in Illumina Miseq Platform. Data processing and bioinformatics analysis were performed via CLC Genomic Workbench bioinformatics tool. The comparison between FAP, UC and control group revealed an alteration in the intestinal microbial composition. More in details, relative abundance of class levels showed statistical significance differences among FAP, UC and control groups. Our preliminary data focused on the explanation of how dysbiosis can lead to inflammation and drive processes together with host genetic profile that leads to colorectal carcinogenesis.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

The latest research cumulates staggering information about the correlation between the microbiota-gut-brain axis and neurodevelopmental disorders. This review aims to shed light on the potential influence of the microbiome on the development of the most prevalent neurodevelopmental disease, attention-deficit-hyperactive disorder (ADHD). As the etiology and pathophysiology of ADHD are still unclear, finding viable biomarkers and effective treatment still represent a challenge. Therefore, we focused on factors that have been associated with a higher risk of developing ADHD while simultaneously influencing the microbial composition. We reviewed the effect of a differing microbial composition on neurotransmitter concentrations important in the pathophysiology of ADHD. Additionally, we deduced factors that correlate with a high prevalence of ADHD while simultaneously affecting the gut microbiome such as emergency c-sections, and premature birth as the former leads to a decrease of the gut microbial diversity and the latter causes neuroprotective Lactobacillus levels to be reduced. Also, we assessed nutritional influences such as breastfeeding, ingestion of short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) on the host’s microbiome and development of ADHD. Finally, we discussed the potential significance of Bifidobacterium as a biomarker for ADHD, the importance of preventing premature birth as prophylaxis and nutrition as a prospective therapeutic measurement against ADHD.

Metformin, the treatment of first choice in type 2 diabetes (T2D), is known to mainly act by decreasing endogenous glucose production (EGP) in the liver. Paradoxically, in the last decade several reports documented increased EGP after metformin treatment. This increase, was often attributed to pronounced rises in glucagon, consistent with counter-regulatory response to the glucose lowering effect of metformin. However, considering that hyperglucagonemia, but not hypoinsulinemia, is a main driver of EGP in T2D, increased EGP should have been a common finding. This observation, together with the finding that metformin antagonizes glucagon effects on energy expenditure and protein synthesis, concurrently to its effects on EGP and the emerging evidences demonstrating increased branched chain and gluconeogenic amino acids in response to metformin treatment may points to a liver alpha-cell skeletal muscle cross talk similar to that observed in the liver-alpha cell axis. Here, we provide a mechanistic perspective to this latter possibility, based on mechanistic studies of metformin’s transcriptional targets; retaining thus its glucagon antagonistic and presumably anti-gluconeogenic effects on liver and attributing the increase in EGP to renal gluconeogenesis. We finally discuss how increased EGP might reflect an adverse response to metformin treatment, providing support from clinical and epidemiological data.

Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease. We aimed to determine the effects of lactoferrin intervention on cognitive function from APP/PS1 mice, and possible mechanisms involved in. Both young and middle-aged male APP/PS1 mice were divided into control and lactoferrin group with 16 weeks’ intervention. Lactoferrin intervention had no effects on cognitive function from both young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered post lactoferrin intervention. In regards to gut microbiota profiles, in the young mice, lactoferrin elevated α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter, in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant post Lf intervention via LEfSe analysis. In the middle-aged mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus and Ruminococcus was significantly reduced post Lf intervention, additionally, S24_7, Bacteroidia, Bacteroidetes and Methylobacterium were specific via LEfSe analysis post lactoferrin intervention. In conclusion, dietary lactoferrin might be beneficial for gut microbiota homeostasis although might have no effects on cognition.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in host which influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics; chemotherapeutic drugs and change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromillieu. Ligands released from dying microbes induce TLR mimicry on interaction with TLR abnormally which skew hypoxia and sterile inflammation contributing to severity of disease like IBD autoimmunity and cancer. Various modalities/interventions practiced across the globe and future strategies for microbiota based therapeutic approaches with special emphasis on tumor and inflammatory diseases are reviewed here. Therefore the major aim and scope of this manuscript is to both discuss various modalities/interventions across the globe and to design future microbiota based therapeutic approaches for mitigating the burden with special emphasis on tumor and Inflammatory diseases.

Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.

As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.

A two-fold integrated research study was conducted; firstly, to understand effects of copper (Cu) and zinc (Zn) on the growth and oxidative stress in Nile tilapia, Oreochromis niloticus; secondly, to study the beneficial effects of the duckweed Lemna minor L. as a heavy metal remover from wastewater. Experiments were conducted in mesocosms with and without duckweed. Tilapia fingerlings were exposed to Cu (0.004 and 0.02 mg/L) and Zn (0.5 and 1.5 mg/L) and fish fed for four weeks. We evaluated the fish growth performance, the hepatic DNA structure using comet assay, the expression of antioxidative genes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx and glutathione-S-transferase, GST) and GPx and GST enzymatic activity. The results showed that Zn exhibited more pronounced toxic effects than Cu. Low dose of Cu did not influence the growth whereas higher doses of Cu and Zn significantly reduced the growth rate of tilapia compared to control, but addition of duckweed prevented weight loss. Further, in the presence of a high dose of Cu and Zn, DNA damage decreased, antioxidant gene expressions and enzymatic activities increased. In conclusion, results suggest that duckweed and Nile tilapia can be suitable candidates in metal remediation wastewater assessment programs.