Alanine Aminotransferase Concentrations Research Articles

Obeticholic acid-loaded exosomes attenuate liver fibrosis through dual targeting of the FXR signaling pathway and ECM remodeling

End-stage of liver fibrosis as a precancerous state could lead to cirrhosis and hepatocellular carcinoma which liver transplantation is the only effective treatment. Previous studies have indicated that farnesoid X receptor (FXR) agonists, such as obeticholic acid (OCA) protect against hepatic injuries. However, free OCA administration results in side effects in clinical trials that could be alleviated by applying bio carriers such as MSC-derived exosomes (Exo) with the potential to mimic the biological regenerative effect of their parent cells, as proposed in this study. Loading OCA into the Exo was conducted via water bath sonication. Ex vivo bio distribution studies validated the Exo-loaded OCA more permanently accumulated in the liver. Using CCL4-induced liver fibrosis, we proposed whether Exo isolated from human Warton’s Jelly mesenchymal stem cells loaded with a minimal dosage of OCA can facilitate liver recovery. Notably, Exo-loaded OCA exerted additive anti-fibrotic efficacy on histopathological features in CCL4-induced fibrotic mice. Compared to baseline, Exo-mediated delivery OCA results in marked improvements in the fibrotic-related indicators as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Accordingly, the synergistic impact of Exo-loaded OCA as a promising approach is associated with the inactivation of hepatic stellate cells (HSCs), extracellular matrix (ECM) remodeling, and Fxr-Cyp7a1 cascade on CCL4-induced liver fibrosis mice. In conclusion, our data confirmed the additive protective effects of Exo-loaded OCA in fibrotic mice, which suggests a valuable therapeutic strategy to combat liver fibrosis. Furthermore, the use of Exo for accurate drug delivery to the liver tissue can be inspiring.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8–21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass.

Objective. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. Methods. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, n = 5). Animals in the control group (CPB-contr, n = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. Results. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, p < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, p < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, p < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; p = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; p = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; p = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. Conclusions. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.

Black soldier fly pulp in the diet of golden pompano: Effect on growth performance, liver antioxidant and intestinal health

Black soldier fly (Hermetia illucens) has been widely researched as a protein source for fish meal replacement in aquaculture, but few studies have focused on its potential as a feed additive for growth and immune enhancement. We conducted a 56-day culture experiment to determine the impact of feed addition of black soldier fly pulp (BSFP, with 86.2% small peptides in dry basis) on growth performance, plasma biochemistry, liver antioxidant levels, intestinal immunity, digestion and microbiota of juvenile golden pompano (Trachinotus ovatus, 5.63 ± 0.02 g). BSFP was added to the basal diet at 0%, 1%, 3%, 5%, 7% and 9% (named Control, BSFP-1, BSFP-3, BSFP-5, BSFP-7, BSFP-9), respectively. BSFP increased the weight gain rate, specific growth rate, protein efficiency ratio and reduced the feed conversion rate of juvenile T. ovatus, the optimal growth performance was reached at BSFP-1, after which a negative feedback phenomenon was observed. Low levels of BSFP upregulated the expression of hepatic antioxidant, intestinal tight junctions, anti-inflammatory related genes and enhanced antioxidant, immune and intestinal digestive enzyme activities, which simultaneously reduced hepatic malondialdehyde and plasma aspartate transaminase and alanine aminotransferase concentrations. However, at BSFP-7, catalase activity was significantly reduced, while NF-κB p65 and pro-inflammatory cytokines transcription was significantly enhanced (P < 0.05). The results suggest that high doses of BSFP addition may damage fish health by inhibiting small peptide uptake, decreasing the activity of antioxidant enzyme and activating the canonical NF-κB pathway. Conversely, low doses of BSFP enhanced intestinal tight junction protein transcription, digestive enzyme activity and immune performance, inhibited pathogenic microbiota, while enhancing liver antioxidant capacity, which was associated with activated Nrf2-Keap1 pathway and suppressed NF-κB pathway, showing its potential as a feed additive to aquafeeds.

Coagulation Abnormalities in Pediatric Patients with β-Thalassemia, An experience at a Tertiary Care Hospital

Life expectancy in thalassemia has markedly improved due to consistent blood transfer and amenability with iron chelation therapy, therefore this improvement is conditioned with various thromboembolic problems of this prolonged disorder including thromboembolic complaints. Objective: To determine coagulation abnormalities in beta (β) thalassemia major patients who have been multi transfused. Methods: This observational study was conducted at Department of Haematology &amp; Transfusion Medicine, Children hospital &amp; University of Child Health Sciences (CH&amp;UCHS), Lahore, from October 2022 to January 2023. The study included 60 β-thalassemic patient, age less than 16 years whose samples were compared with upper and lower normal value as regards to Prothrombin Time (PT), Active Partial Thromboplastin Time (APTT), Protein S, Protein C, liver enzymes (Alanine Transaminase (ALT), Aspartate Transaminase (AST), Gamma-Glutamyl Transferase (GGT). The data were analyzed using IBM SPSS version 23.0. Results: When values were compared, natural clotting inhibitors (Protein S, Protein C) were remarkably reduced in β-thalassemic paeds patients (p&lt;0.001).PT and APTT were prolonged in thalassemic children (p&gt;0.05 and p&lt;0.05 correspondingly). There was substantial increase in concentrations of ALT and AST in β-thalassemic patients (p &lt; 0.001 and p &lt; 0.001 respectively) due to iron over load by multiple transfusions. Conclusions: Marked changes in coagulation inhibition supporting thrombotic tendency was observed in thalassemic children. There were reduced levels of protein C and protein S, independent of slightly prolonged PT and APTT and elevated levels of ALT, AST with normal GGT in thalassemic children.

Telomere length and risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma in 63,272 individuals from the general population.

Inherited short telomeres are associated with a risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of HCC and cholangiocarcinoma remains unknown. We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and plasma ALT concentration were not associated (β = 4 ×10 -6 , p -value = 0.06) in a linear regression model, without any signs of a nonlinear relationship. We tested the association between telomere length and risk of cirrhosis, HCC, and cholangiocarcinoma using Cox regression. During a median follow-up of 11 years, 241, 76, and 112 individuals developed cirrhosis, HCC, and cholangiocarcinoma, respectively. Telomere length and risk of cirrhosis were inversely and linearly associated ( p -value = 0.004, p for nonlinearity = 0.27). Individuals with telomeres in the shortest vs. longest quartile had a 2.25-fold higher risk of cirrhosis. Telomere length and risk of HCC were nonlinearly associated ( p -value = 0.009, p -value for nonlinearity = 0.01). This relationship resembled an inverted J-shape, with the highest risk observed in individuals with short telomeres. Individuals with telomeres in the shortest versus longest quartile had a 2.29-fold higher risk of HCC. Telomere length was inversely and linearly associated with the risk of cholangiocarcinoma. Individuals with telomeres in the shortest versus longest quartile had a 1.86-fold higher risk of cholangiocarcinoma. Shorter telomere length is associated with a higher risk of cirrhosis, HCC, and cholangiocarcinoma.

Effect of dietary glycine supplementation on productive performance, egg quality, stress response, and fatty liver incidence in laying hens raised under heat stress conditions

The current experiment aimed to investigate the effect of dietary glycine (Gly) supplementation on productive performance, egg quality, stress response, and fatty liver incidence in laying hens raised under heat stress (HS) conditions. A total of two hundred eighty 24-wk-old Lohmann Brown-Lite laying hens were randomly allotted to 1 of 4 dietary treatments with 7 replicates. The negative control (NC) diet was prepared to meet or exceed the nutrient and energy requirement for Lohmann Brown laying hens, whereas the positive control (PC) diet was formulated to increase AMEn by 100 kcal/kg compared with the NC diet. Two additional diets were prepared by supplementing 0.341% and 0.683% Gly to the NC diet. All hens were exposed to cyclic HS at 31.4 ± 1.17°C for 8 h/d and 26.7 ± 1.10°C for the remaining time for a 12-wk trial. Results indicated that increasing supplementation of Gly in diets tended (linear, P=0.088) to decrease the FCR of laying hens. Increasing supplementation of Gly in diets increased (linear, P < 0.05) eggshell lightness and decreased (linear, P < 0.05) egg yolk color. Moreover, a tendency for a quadratic association (P < 0.10) of serum aspartate aminotransferase and alanine aminotransferase concentrations with increasing supplementation of Gly was observed. Increasing supplementation of Gly in diets decreased (linear, P < 0.05) blood heterophil:lymphocyte ratio of laying hens. Hens fed the NC diet showed higher fatty liver incidence (P < 0.05) than those fed the PC diet, but increasing supplementation of Gly decreased (linear, P < 0.05) fatty liver incidence of laying hens. In conclusion, increasing supplementation of Gly up to 0.683% in diets decreases FCR, stress response, and fatty liver incidence in laying hens raised under HS conditions.

Aminotransferase Activity Measurement on The Atellica® CH 930 and The Architect® ci4100

The Atellica® CH 930 is a new biochemistry analyzer recently introduced to the world market. This study aims to compare the Atellica® CH 930 analyzer to the Architect® ci4100 analyzer for measurement of serum aspartate (AST) and alanine (ALT) aminotransferase concentrations. A total of 112 sera were tested on the Architect® ci4100 and the Atellica® CH 930 analyzers for ALT and AST activities, and the results were compared using the paired Student's t-test, Pearson’s correlation analysis, Passing-Bablok regression analysis, and Bland–Altman plots. There was no significant difference between the means of the ALT and AST concentrations measured using the two instruments (p = 0.659 and p = 0.506, respectively). For ALT, the Passing-Bablok equation was Atellica=1.11 ×Architect -0.96, with a correlation coefficient (r) of 0.999. For AST, it was Atellica=1.08 ×Architect -0.50, with r = 0.998. According to Bland-Altman plots, the mean difference between both methods was 2.3 IU/L (4.3%) for ALT and 2.1 IU/L (5.8%) for AST, with 95.53% and 96.43% of points within the interval [0 ± 1.96 × SD], respectively. These findings demonstrated that the Atellica® CH 930 and Architect® ci4100 methods had an overall good agreement in aminotransferase measurement.

Comparative effect of ginger (an anti-inflammatory medicinal herb) and aspirin (a non-steroidal anti-inflammatory drug) on liver enzymes in male albino Wistar rats

Background:Herbal therapies mediate similar functions with those of some well-known drugs. Ginger and aspirin are herbal and drug therapies respectively which are used for the treatment of anti-inflammatory conditions. Non-steroidal medicinal drugs especially aspirin and acetaminophen are usually linked to drug-induced liver injury. Therefore, this research seeks to compare the effect of these two therapies on liver function using aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as the biomarkers. The aim of the study was to establish if ginger will offer a better hepatocellular protection considering that the use of aspirin in treating inflammatory disorders is already linked to liver injury.&#x0D; Methods: AST, ALT, ALP, Total, conjugated and unconjugated bilirubin were assessed in this study using 18 Wistar rats. The animals were divided into three groups (control, ginger and aspirin), six (6) rats per group. The three groups of animals were allowed access to food and water daily throughout the experimental period. Ginger group animals were administered 150 mg/kg dose of aqueous ginger extract while aspirin group of animals also received 150 mg/kg dose of aspirin for four weeks. Control group received normal saline of equal volume with the test groups.&#x0D; Results: AST, ALT, total and conjugated bilirubin was significantly lower in ginger group compared to aspirin and the control group (P&lt;0.05). However, ALP was significantly higher in ginger group compared to aspirin and the control group (P&lt;0.05). Unconjugated bilirubin showed no significant difference among experimental groups.&#x0D; Conclusion: Result showed that ginger offered a better hepatocellular protection compared to aspirin group following decrease AST and ALT concentration in the ginger group.

Evaluation of dietary supplementation of frankincense oil on broiler chicken growth performance, hepatic histomorphology, antioxidant activity, blood biochemical parameters, and inflammatory responses

This investigation aimed to assess the potential impact of frankincense oil (FKO) from Boswellia serrata on broiler chicken growth performance parameters, including body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) during the starter, grower, and finisher phases. We also evaluated the hepatic histology, serum hepatorenal function tests, antioxidant activity, and inflammatory responses. A total of 400 three-day-old male chicks (Ross 308 broiler) (100.40 ± 0.13 g) were randomly assigned to four treatment groups (10 replicates/group, ten chicks/replicate). The birds were fed basal diet (FKO0, control group) or basal diet supplemented with 200, 400, and 600 FKO/kg of diet (FKO200, FKO400, FKO600, respectively). The experiment lasted 35 days. Gas chromatography-mass spectrometry analysis revealed that FKO contained 36 constituents, with the dominant compounds being 1,6,10-DODECATRIEN-3-OL, 3,7,11-TRIMETHYL-, [S-(Z)]- (12.42%), ç-Elemene (12.42%), à-Farnesene (12.42%), PHENOL and 2,4-BIS(1,1-DIMETHYLETHYL)- (7.15%). Distinctive FKO levels (200-600 mg/kg) showed greater BW without influencing total feed intake compared to the FKO0 treatment. The FCR was improved by the addition of FKO to the diets. The blood concentrations of alanine aminotransferase and creatinine increased (p < 0.05) in the FKO600 treatment. Dietary FKO linearly lowered serum malondialdehyde levels and enhanced blood total antioxidant capacity, catalase, superoxide dismutase, and pro-inflammatory cytokines (interleukine-1 β and interferon γ) compared to the control group. Broilers fed FKO at levels 200–600 mg kg−1 diet also exhibited lower serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, the FKO400 and FKO600 treatments showed an increase in high-density lipoprotein cholesterol (p < 0.01). Histomorphological analysis of the liver indicated no significant differences between the FKO-supplemented groups and the control group. However, the immunoexpression of the pro-inflammatory cytokine (transforming growth factor β) was considerably increased in the liver and spleen tissues of birds fed FKO in a level-dependent manner. In conclusion, dietary supplementation of FKO at levels up to 600 mg/kg can serve as a natural growth promoter in broiler chickens, leading to enhanced growth, hypolipidemic properties, antioxidant status, and immune responses.

Short-Term Exposure to PM2.5 and O3 Impairs Liver Function in HIV/AIDS Patients: Evidence from a Repeated Measurements Study.

Studies investigating the relationship between ambient air pollutants and liver function are scarce. Our objective was to examine the associations of acute exposure to PM2.5 and O3 with levels of hepatic enzymes in people living with HIV/AIDS (PWHA). Our study involved 163 PWHA, who were evaluated for serum hepatic enzymes up to four times within a year. We extracted daily average concentrations of PM2.5, PM2.5 components, and O3 for each participant, based on their residential address, using the Tracking of Air Pollution in China database. Linear mixed-effect models were utilized to assess the associations of acute exposure to PM2.5 and O3 with hepatic enzymes. Weighted quantile sum regression models were employed to identify the major constituents of PM2.5 that affect hepatic enzymes. The percent change of aspartate aminotransferase (AST) concentration was positively correlated with a 10 µg/m3 increase in PM2.5, ranging from 1.92 (95% CI: 3.13 to 4.38) to 6.09 (95% CI: 9.25 to 12.38), with the largest effect observed at lag06. Additionally, acute O3 exposure was related to increased levels of alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) concentrations. Co-exposure to high levels of PM2.5 and O3 had an antagonistic effect on the elevation of AST. Further analysis revealed that SO42- and BC were major contributors to elevated AST concentration due to PM2.5 constituents. A stronger association was found between O3 exposure and ALT concentration in female PWHA. Our study found that short-term exposure to PM2.5 and O3 was associated with increased levels of hepatic enzymes, indicating that PM2.5 and O3 exposure may contribute to hepatocellular injury in PWHA. Our study also found that PWHA may be more vulnerable to air pollution than the general population. These findings highlight the relationship between air pollutants and liver function in PWHA, providing a scientific basis for the implementation of measures to protect susceptible populations from the adverse effects of air pollution. A reduction in the burning of fossil fuels and reduced exposure to air pollutants may be effective hazard reduction approaches.

Water Extract of Rice False Smut Balls Activates Nrf2/HO-1 and Apoptosis Pathways, Causing Liver Injury

Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. The toxicity of the water extract of rice false smut balls (RBWE) remains to be investigated. Studies have shown that RBWE may be toxic to animals, but toxicological evidence is still lacking. In this study, we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/mL, respectively, with positive correlations with dose toxicity and time toxicity. After treatment with RBWE, the number of BNL CL.2 cells decreased significantly, and the morphology of BNL CL.2 cells showed atrophy and wall detachment. RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells, increased the proportion of apoptotic cells and inhibited cell proliferation. RBWE up-regulated reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials. Additionally, Western blot and qRT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo. The contents of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE. At the same time, RBWE can lead to increases in ROS and malondialdehyde contents, decreases in contents of oxidized glutathione, glutathione and reduced glutathione, as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues, demonstrating that oxidative stress occurred in mice. Moreover, liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE. In general, RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway, which provides a reference for hepatotoxicity and its mechanism of action.

Gut ecological networks reveal associations between bacteria, exercise, and clinical profile in non-alcoholic fatty liver disease patients.

Gut microbial dysbiosis has been observed in non-alcoholic fatty liver disease (NAFLD). The beneficial impact of exercise, the recommended lifestyle change for NAFLD patients, might be mediated by the gut microbiome (GM). However, the exact taxonomic and functional signatures associated with the host's clinical and biochemical improvement during exercise in NAFLD patients have not been elucidated yet. To investigate the impact of exercise on GM and reveal GM structures associated with NAFLD improvement during exercise. Stool samples from a 12-week randomized controlled exercise study on NAFLD subjects (N = 39) were retrieved, and shotgun metagenomics was performed at baseline and endpoint. Differential correlation network and enrichment analysis were applied to characterize the GM taxonomic and functional changes during the exercise intervention and to associate GM changes with biomarkers of liver status and metabolic dysregulation. Network analysis demonstrated that exercise induced significant changes in the bacterial interactome, which were associated with waist circumference; resting metabolic rate; plasma fasting concentrations of triglyceride, glucose, insulin, and glycated hemoglobin A1c; and homeostasis model assessment for insulin resistance. Grouping the patients in the exercise group (N = 20) as responders (N = 13) and non-responders (N = 7) using their intrahepatic lipid content (IHL) change allowed us to identify bacteria consortia contributing to the levels of alanine fermentation, methanol-, creatinine-, and protocatechuate degradation and as a result to the plasma concentrations of liver injury markers alanine transaminase, gamma-glutamyl transaminase, and aspartate transaminase. We showed that even though exercise has not a significant impact on the alpha- and beta-diversity of NAFLD patients, it leads to a significant re-structuring of the gut bacteria interactome and that specific structural changes can be linked with improvements in IHL. IMPORTANCE Our study is applying a community-based approach to examine the influence of exercise on gut microbiota (GM) and discover GM structures linked with NAFLD improvements during exercise. The majority of microbiome research has focused on finding specific species that may contribute to the development of human diseases. However, we believe that complex diseases, such as NAFLD, would be more efficiently treated using consortia of species, given that bacterial functionality is based not only on its own genetic information but also on the interaction with other microorganisms. Our results revealed that exercise significantly changes the GM interaction and that structural alterations can be linked with improvements in intrahepatic lipid content and metabolic functions. We believe that the identification of these characteristics in the GM enhances the development of exercise treatment for NAFLD and will attract general interest in this field.

Association between Asia–Pacific body mass index classification and serum liver enzymes: alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in healthy individuals

BackgroundElevated levels of serum liver transaminases are good indicators of liver cell damage, and elevated serum gamma-glutamyl transferase (GGT) level is a good indicator of both bile duct and hepatocellular damage. At early stages, elevated serum levels of these liver enzymes can be mostly prevailed as an asymptomatic condition and therefore in an undiagnosed state. This may be resulted in a number of complications and may lead to chronic hepatic damage that will be more severe and difficult to care. Serum liver enzyme levels are affected by age, gender, body mass index (BMI), ethnicity, drugs and viruses. Obesity has been an epidemic in nearly every country in the world. BMI is the best parameter to assess the magnitude of obesity. Having this background, the present study was designed to investigate the correlation between the levels of serum liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GGT and Asia–Pacific cut-off points of BMI in healthy individuals.MethodsA descriptive cross-sectional study was conducted using 120 Sinhala, Buddhist subjects which belonged to 18–32 years. BMI was calculated according to the standard protocol. The serum ALT and AST concentrations were measured by UV assay according to the IFCC method without pyridoxal phosphate activation, and the serum GGT concentration was measured by UV assay according to Szasz method, using the Mindray BS-240 Full Automatic Biochemistry Analyser.ResultsSerum levels of liver enzymes were significantly higher in males than females. In females, serum levels of ALT (r = 0.312, p < 0.001), AST (r = 0.138, p = 0.071) and GGT (r = 0.212, p = 0.047) positively correlated with BMI. In males too, serum levels of ALT (r = 0.431, p < 0.001), AST (r = 0.324, p = 0.013) and GGT (r = 0.314, p = 0.031) were positively correlated with BMI. The minimum values of serum ALT, AST and GGT levels were observed in underweight group, while the maximum values were observed in obese group in both genders.ConclusionsALT had the strongest correlation with BMI in both females and males. Therefore, ALT can be suggested as the best liver enzyme that can be used in screening purposes by concerning BMI.

A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase-based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia.

Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT-based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX-induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia. A retrospective study was conducted on paediatric patients who received high-dose (3-5g/m2 ) MTX treatment. MTX concentrations were assessed at 24-h intervals until the concentration dropped below 0.1μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semimechanistic hepatotoxicity model. The PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a 2-compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable interoccasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters. A semimechanistic model was developed to describe ALT-based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug-induced hepatotoxicity.

The Protective Effects of the Echium amoenum Seed Oil Against Seizures Induced by Pentylenetetrazole

Background: Many recent studies have documented that polyunsaturated fatty acids (PUFAs) as a safe supplement raise seizure thresholds. However, the evidence of seed oil supplements on seizure susceptibility remains controversial, and among them, Echium seed oil (EO) is a mixture of ω-3 and ω-6 PUFAs. Objectives: This study aimed to test the effects of the sub-chronic administration of EO on intravenous pentylenetetrazole (PTZ) seizure threshold, considering its antioxidant activity and biochemical parameters. Methods: Fifty male mice were divided into five groups (10 in each), including control (no treatment), vehicle (sesame oil), and EO (1, 3, and 5 g/kg) groups. Vehicle and EO were administered p.o. once a day for four weeks. Then, the intravenous PTZ induced-seizure threshold was determined. Finally, the serum concentration of lipid, creatinine, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and the activity of superoxide dismutase (SOD) was assessed. Results: Pretreatment with EO raised the seizure threshold dose-dependently compared to the vehicle. Pretreatment with EO had no adverse effect on the serum concentration of ALP, AST, ALT, creatinine, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), but at the dosages of 3 and 5 g/kg decreased the concentration of cholesterol, very low-density lipoprotein (VLDL) (P &lt; 0.05), and triglyceride (TG) (P &lt; 0.01). Also, 1 and 3 g/kg of EO improved the activity of SOD (P &lt; 0.01). Conclusions: Pretreatment with EO increases the seizure threshold without negative impacts on the liver and kidney biomarkers, correlated with its positive effects on antioxidant activity and serum lipid profiles.

Effects of different sodium acetate levels on growth, antioxidant capacity, and fat deposition in juvenile Onychostoma macrolepis fed a high fat diet

Effects of different sodium acetate levels on growth, antioxidant capacity, and fat deposition in juvenile <i>Onychostoma macrolepis</i> fed a high fat diet

Genetics of Plasma Bilirubin and Associations between Bilirubin and Cardiometabolic Risk Profiles in Danish Children and Adolescents.

Bilirubin is the end product of heme catabolism, mainly produced by the breakdown of mature red blood cells. Due to its anti-inflammatory, antioxidant, antidiabetic, and antilipemic properties, circulating bilirubin concentrations are inversely associated with the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality in adults. Some genetic loci associated with circulating bilirubin concentrations have been identified by genome-wide association studies in adults. We aimed to examine the relationship between circulating bilirubin, cardiometabolic risk factors, and inflammation in children and adolescents and the genetic architecture of plasma bilirubin concentrations. We measured fasting plasma bilirubin, cardiometabolic risk factors, and inflammatory markers in a sample of Danish children and adolescents with overweight or obesity (n = 1530) and in a population-based sample (n = 1820) of Danish children and adolescents. Linear and logistic regression analyses were performed to analyze the associations between bilirubin, cardiometabolic risk factors, and inflammatory markers. A genome-wide association study (GWAS) of fasting plasma concentrations of bilirubin was performed in children and adolescents with overweight or obesity and in a population-based sample. Bilirubin is associated inversely and significantly with a number of cardiometabolic risk factors, including body mass index (BMI) standard deviation scores (SDS), waist circumference, high-sensitivity C-reactive protein (hs-CRP), homeostatic model assessment for insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), triglycerides, and the majority of measured inflammatory markers. In contrast, bilirubin was positively associated with fasting plasma concentrations of alanine transaminase (ALT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SDS), and the inflammatory markers GH, PTX3, THBS2, TNFRSF9, PGF, PAPPA, GT, CCL23, CX3CL1, SCF, and TRANCE. The GWAS showed that two loci were positively associated with plasma bilirubin concentrations at a p-value threshold of <5 × 10-8 (rs76999922: β = -0.65 SD; p = 4.3 × 10-8, and rs887829: β = 0.78 SD; p = 2.9 × 10-247). Approximately 25% of the variance in plasma bilirubin concentration was explained by rs887829. The rs887829 was not significantly associated with any of the mentioned cardiometabolic risk factors except for hs-CRP. Our findings suggest that plasma concentrations of bilirubin non-causally associates with cardiometabolic risk factors in children and adolescents.

Machine learning to predict pediatric choledocholithiasis: A Western Pediatric Surgery Research Consortium retrospective study

BackgroundThe purpose of this study was to accurately predict pediatric choledocholithiasis with clinical data using a computational machine learning algorithm. MethodsA multicenter retrospective cohort study was performed on children <18 years of age who underwent cholecystectomy between 2016 to 2019 at 10 pediatric institutions. Demographic data, clinical findings, laboratory, and ultrasound results were evaluated by bivariate analyses. An Extra-Trees machine learning algorithm using k-fold cross-validation was used to determine predictive factors for choledocholithiasis. Model performance was assessed using the area under the receiver operating characteristic curve on a validation dataset. ResultsA cohort of 1,597 patients was included, with an average age of 13.9 ± 3.2 years. Choledocholithiasis was confirmed in 301 patients (18.8%). Obesity was the most common comorbidity in all patients. Choledocholithiasis was associated with the finding of a common bile duct stone on ultrasound, increased common bile duct diameter, and higher serum concentrations of aspartate aminotransferase, alanine transaminase, lipase, and direct and peak total bilirubin. Nine features (age, body mass index, common bile duct stone on ultrasound, common bile duct diameter, aspartate aminotransferase, alanine transaminase, lipase, direct bilirubin, and peak total bilirubin) were clinically important and included in the machine learning algorithm. Our 9-feature model deployed on new patients was found to be highly predictive for choledocholithiasis, with an area under the receiver operating characteristic score of 0.935. ConclusionThis multicenter study uses machine learning for pediatric choledocholithiasis. Nine clinical factors were highly predictive of choledocholithiasis, and a machine learning model trained using medical and laboratory data was able to identify children at the highest risk for choledocholithiasis.

Effects of bacteriophage on Salmonella Enteritidis infection in broilers

Bacteriophages (BP) are viruses that can infect bacteria. The present study evaluated the effect of BP on Salmonella infected broilers. A number of 150 day-old broilers were used in a completely randomized design with five treatments that included: (1) basal diet from day 0 to 28; (2) basal diet + 0.3 g/kg of colistin from day 0 to 28; (3) basal diet from day 1 to 13, and basal diet + 0.4 g/kg of colistin from day 14 to 28; (4) basal diet + 1 g/kg of BP from day 0 to 28; (5) basal diet + 1.5 g/kg of BP from day 0 to 28. On day 13, 15 chickens from each treatment were challenged by Salmonella Enteritidis (SE), while fifteen from each treatment were not; instead, they were kept in the same cage with the challenged chickens (exposed chickens). At 7 and 14 days post-challenge, the number of SE and coliform bacteria in the cecum and liver of colistin and BP-fed birds was lower than the control treatment. In exposed and challenged chickens, the height and surface area of villus were greater in the BP and colistin-supplemented groups. Serum concentrations of aspartate aminotransferase and alanine transaminase were greater, while serum albumin and triglycerides concentrations were lower in the control treatment. The liver of the challenged chickens had more pathological lesions than exposed birds. BP significantly decreased PPARγ gene expression in exposed chickens. In the challenged and exposed chickens, TLR4 gene expression was lower in BP and colistin-treated birds as compared to the control. In conclusion, adding BP to the diet from the day of age prevents the spread of Salmonella.