Serum Alanine Aminotransferase Research Articles

Effects of Dietary Calcium Lactate Supplementation on Laying Performance, Blood Index, Shinbone Quality, Jejunal Immunity, and Egg Quality of Aged Laying Hens

This study aimed to verify the potential of calcium lactate for the performance, blood index, shinbone quality, jejunal immunity, and egg quality of aged laying hens. A total of 360 62-week-old Hy-Line Brown laying hens were randomly divided into four treatments, with six replicates and 15 chickens per replicate. Experimental groups were fed with 0.25%, 0.5%, and 1.0% calcium lactate to substitute limestone in the control group (maintaining the same amount of calcium). The feeding trial lasted for 12 weeks. The laying rate and daily egg mass of laying hens fed the diets supplemented with calcium lactate was increased relative to those of the control group. The dietary addition of calcium lactate for laying hens enhanced the eggshell ratio, eggshell thickness, eggshell strength, and albumen height of eggs, and the addition level of 0.5% had the best effect. Dietary calcium lactate increased the number of red blood cells, corpuscular hemoglobin, mononuclear leucocytes and basophilic granulocytes, and decreased heterophils in the blood of laying hens. The activities of serum alanine transaminase and creatine kinase in laying hens was reduced by the dietary addition of calcium lactate. Calcium lactate supplementation in diets increased the serum calcium and phosphorus contents of laying hens. The dietary inclusion of calcium lactate increased the contents of IgA, IgG, lysozyme, and sIgA in the jejunal mucosa, and the 0.5% addition level worked best, but the IL-2 content decreased. The addition of 0.5% calcium lactate to the diet reduced the maximal force of the shinbone and increased the work required for shinbone rupture in laying hens. In conclusion, the dietary addition of calcium lactate improved the performance and egg quality of laying hens, probably by its positive effects on body health, intestinal digestible ability, calcium bioavailability, and jejunal mucosal immunity. The optimum amount of calcium lactate in the diet of laying hens is recommended to be 0.5%.

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity

BackgroundNonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PurposeThis study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. MethodsA NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. ResultsIn MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1β, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFβ, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. ConclusionOur study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.

Efficacy of Ganshuang granules on non-alcoholic fatty liver and underlying mechanism: a network pharmacology and experimental verification.

To investigate the potential pharmacological mechanisms of Ganshuang granules (, GSG) in treating non-alcoholic fatty liver (NAFLD). All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Protein-Protein interaction network, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD. Then, the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG. The levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot, respectively. Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD. Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD. Further experiments showed that the significantly decreased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment, as well as the expression levels of IL-6 and TNF-α in the liver. Furthermore, drug intervention increased the protein expression levels of phosphorylated-PI3K (P-PI3K) and P-AKT in the liver of the model group mice, and decreased the protein expression level of sterol regulatory element-binding protein 1. We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

Effect of recombinant human thrombopoietin on platelets in rats with D-galactosamine salt-induced acute liver failure

To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF. Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1 500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 μg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×109/L): 1 673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×109/L): 1 350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.

Chishao (Paeoniae Radix Rubra) alleviates intra-hepatic cholestasis by modulating NTCP in rats.

Background: Cholestasis is a common pathological manifestation dominated by accumulation of potentially toxic biliary compounds. Na+-taurocholate cotransporting polypeptide (NTCP) plays a critical role in protection from cholestasis and can be targeted therapeutically. Chishao (Paeoniae Radix Rubra) is a clinically efficacious agent for treating cholestasis, but the underlying mechanism has not been fully clarified. Objective: To evaluate the effects of Chishao on the expression of NTCP in rats with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. Methods: Chishao extracts were obtained by water decoction. Cholestasis model induced by ANIT in rats were established. Thirty rats were divided into five groups: control group (C), ANIT model group (M), 10g/kg Chishao group (LD), 20g/kg Chishao group (MD) and 40g/kg Chishao group (HD). The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP) and total bile acid (TBA) were detected. The mRNA and protein expression of NTCP, multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) were detected by reverse transcription qPCR and Western blotting respectively. To assess the effects of Chishao on NTCP, MRP2 and BSEP localized at the membrane of hepatocytes, an in vitro experiment involving primary hepatocytes was conducted via the utilization of laser scanning confocal microscopy. Results: The extracts of Chishao significantly improved serum ALT, AST, ALP, TB, DB and TBA (p < 0.05), especially ALP in the HD group (p < 0.01). The histological pathological findings were also reversed in LD, MD and HD groups. The mRNA level of MRP2 was significantly downregulated after treatment with ANIT, whereas it was reversed in MD and HD groups (p < 0.05). The mRNA expression of NTCP was significantly downregulated after ANIT treatment, but dramatically upregulated in the HD group. The expressions of BSEP and MRP2 were similar, but that of NTCP decreased after ANIT treatment, which was reversed significantly by Chishao extracts in a dose-dependent manner. The expression of NTCP in hepatocytes from rats increased dose-dependently after Chishao treatment in vitro. Conclusion: Chishao extracts can improve the serum and histological performances of intra-hepatic cholestasis caused by ANIT, probably by working on transport proteins in liver cell membranes.

Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis. A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded. A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge. Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences.

Effect of dietary methionine hydroxy analogue‐free acid (MHA‐FA) supplementation levels on growth performance, blood metabolites and immune responses in broiler chickens

AbstractBackgroundBroiler diets are commonly supplemented by liquid methionine hydroxy analogue‐free acid (MHA‐FA) containing as product with 88% of active substance to meet sulphur amino acid (SAA) requirements.ObjectivesTwo experiments were conducted to assess the effects of different dietary MHA‐FA levels on growth performance, blood metabolites and immune responses in broilers.MethodsIn experiments 1 and 2, 432 and 360 male broilers were fed either a basal corn–soya bean meal diet that met the energy and nutrient requirements with the exception of SAAs or the basal diet supplemented with 5 graded levels of MHA‐FA (+0.9 and +0.8 g/kg), for 1–11 and 11–24‐day ages, respectively. Chicks were vaccinated with inactivated H9N2/Newcastle disease (ND) and live‐ND on days 5 and 11, respectively.ResultsResponses in both experiments had similar tendency at corresponding dietary MHA‐FA levels. By increasing dietary MHA‐FA level, weight gain (WG), feed efficiency (FE), relative breast weight (RBW) and immunity against ND and avian influenza virus inoculation improved with quadratic trend. Blood serum triglyceride, low‐density lipoprotein, alanine aminotransferase and alkaline phosphatase concentration were affected in response to dietary MHA‐FA levels with quadratic trends. By using broken‐line regression analysis, the optimum dietary MHA‐FA levels for optimized WG, FE and RBW during 1–10‐day age were obtained at 2.20, 3.31 and 3.33 g/kg, respectively; based on MHA‐FA content of Met equivalent, the digestible SAA requirements were estimated 0.81%, 0.91% and 0.92%, respectively. Similarly, for the 11–24‐day age period, the optimum dietary MHA‐FA supplementation levels were obtained 1.79, 2.21, 2.41 and 2.53 g/kg, with the digestible SAA requirements estimated 0.75%, 0.79%, 0.80% and 0.81% for optimized WG, FE, RBW and immune responses, respectively.ConclusionsSupplemental levels of MHA‐FA that optimize performance, breast meat and immunity in broilers fed corn–soya bean meal diet, varied from 0.18% to 0.33%, correspond to age and what traits are considered for optimization.

Investigation of the effects of white tea on liver fibrosis: An experimental animal model.

Liver fibrosis is a common, progressive disease that affects millions of patients worldwide. In this study, it was aimed at investigating the effect of white tea on liver fibrosis in an in-vivo environment by creating an experimental liver fibrosis model on rats. In this study, an experimental liver fibrosis model was created with carbon tetrachloride (CCl4) in Sprague-Dawley rats to investigate the effect of white tea on liver fibrosis. Rats are treated with CCl4 (1 mL/kg) to constitute the liver fibrosis model. White tea was given adlibitum with drinking water. As a result of the study, liver tissue hydroxyproline levels were found to be significantly lower (p = .001) in the white tea group. Histopathologically, it was found that the liver tissue histopathological damage score (LHDS) and fibrosis scoring were significantly lower (p < .001) in the white tea group. However, although it was not statistically significant in the group given white tea, compared with the fibrosis group, it was found that the malondialdehyde (MDA) level in the liver tissues was lower, the glutathione (GSH) level was higher, and the serum alanine aminotransferase (ALT) levels were lower. The study explained the effect of white tea on liver fibrosis and suggested that white tea might be beneficial in reducing the progression of liver fibrosis.

Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.

Noninvasive Monitoring of Severe Pulmonary Artery Hypertension in Atrial Septal Defect Patients: Role of Serum Bilirubin Combined with Uric Acid.

Atrial septal defect (ASD) patients commonly experience severe pulmonary arterial hypertension (SPAH), which is frequently associated with a poor prognosis. While serum bilirubin levels, indicative of liver function, are known predictors of right heart failure (RHF), their potential to differentiate SPAH in ASD patients is yet to be ascertained. The purpose of this study was to discover the potential correlations between serum bilirubin levels and ASD patients with SPAH. In this cross-sectional study, 102 ASD patients admitted from December 2019 to November 2020 were enrolled and divided into two cohorts: those with SPAH and those without. Blood tests were conducted to measure serum direct bilirubin (DBIL), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Additionally, all participants underwent transthoracic echocardiography, and invasive hemodynamic data were gathered through right heart catheterization. ASD patients with SPAH exhibited significantly elevated serum DBIL (5.2 3.0 vs. 2.4 1.5 µmol/L, p 0.001) and TBIL (24.6 20.7 vs. 10.1 4.8 µmol/L, p 0.001) levels in comparison to those without SPAH. However, ALT and AST levels remained comparable between the cohorts. Additionally, the SPAH cohort displayed higher serum UA (403.5 131.6 vs. 317.8 67.9 µmol/L, p 0.001) and NT-proBNP levels. Serum DBIL levels, when analyzed independently of other variables, correlated with an increased risk of mean pulmonary arterial pressure (mPAP) in ASD patients ( = 1.620, p = 0.010). A DBIL concentration of 2.15 mg/dL effectively differentiated ASD patients with SPAH from those without, with a sensitivity of 92.9% and a specificity of 51.4% (area under the curve [AUC]: 0.794, 95% confidence interval [CI]: 0.701-0.886, p 0.001). Notably, the combination of DBIL and UA had a higher sensitivity of 92.9% and specificity of 71.6% (AUC: 0.874, 95% CI: 0.799-0.949, p 0.001). Elevated serum DBIL and TBIL levels in ASD patients with SPAH were correlated with poor cardiac function and heightened pulmonary artery pressure. The combination of DBIL and UA has emerged as a strong noninvasive predictor for SPAH in ASD patients, presenting a potentially novel therapeutic biomarker.

Interleukin 28A aggravates Con A-induced acute liver injury by promoting the recruitment of M1 macrophages.

Immune-mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin-28A (IL-28A), a member of the IL-10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL-28A, its role in immune-mediated acute injury remains unclear. The present study investigated the role of IL-28A in concanavalin A (Con A)-induced acute immune liver injury. After Con A injection in mice, IL-28A level significantly increased. IL-28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL-28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL-28A-deficiency group than in the wild-type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL-28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-12, IL-6, and IL-1β, by M1 macrophages decreased significantly in the IL-28A-deficiency group. Western blotting demonstrated that IL-28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL-28A deletion plays an important protective role in the Con A-induced acute liver injury model and IL-28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF-κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune-related hepatic injury.

Traditional Chinese Medicine formula Dai-Zong-Fang alleviating hepatic steatosis in db/db mice via gut microbiota modulation.

Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis. Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR. Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂). Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism.

Curdlan-Decorated Fullerenes Mitigate Immune-Mediated Hepatic Injury for Autoimmune Hepatitis Therapeutics via Reducing Macrophage Infiltration.

Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease whose standard of care is immunosuppressive treatment with inevitable undesired outcomes. Macrophage is acknowledged to aggravate liver damage, providing a promising AIH therapeutic target. Accordingly, in this study, a kind of curdlan-decorated fullerene nanoparticle (Cur-F) is fabricated to alleviate immune-mediated hepatic injury for treating AIH via reducing macrophage infiltration in a concanavalin A (Con A)-induced AIH mouse model. After intravenous administration, Cur-F primarily distributes in liver tissues, efficiently eliminates the excessive reactive oxygen species, significantly attenuates oxidative stress, and subsequently suppresses the nuclear factor kappa-B-gene binding (NF-κB) signal pathway, resulting in the lowered production of pro-inflammatory cytokines and the balancing of the immune homeostasis with the prevention of macrophage infiltration in the liver. The regulation of hepatic inflammation contributes to inhibiting inflammatory cytokines-induced hepatocyte apoptosis, decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents and thus ameliorating immune-mediated hepatic injury. Notably, there is no detectable toxicity to the body. Our findings may open up novel avenues for AIH based on curdlan and fullerene materials.

Serum alanine aminotransferase: Are we still far from a one-size-fits-all pediatric reference cutoff strategy?

Serum alanine aminotransferase: Are we still far from a one-size-fits-all pediatric reference cutoff strategy?

Time-Restricted Feeding Ameliorates Methionine-Choline Deficient Diet-Induced Steatohepatitis in Mice.

Non-alcoholic steatohepatitis (NASH) is an inflammatory form of non-alcoholic fatty liver disease (NAFLD), closely associated with disease progression, cirrhosis, liver failure, and hepatocellular carcinoma. Time-restricted feeding (TRF) has been shown to decrease body weight and adiposity and improve metabolic outcomes; however, the effect of TRF on NASH has not yet been fully understood. We had previously reported that inositol polyphosphate multikinase (IPMK) mediates hepatic insulin signaling. Importantly, we have found that TRF increases hepatic IPMK levels. Therefore, we investigated whether there is a causal link between TRF and IPMK in a mouse model of NASH, i.e., methionine- and choline-deficient diet (MCDD)-induced steatohepatitis. Here, we show that TRF alleviated markers of NASH, i.e., reduced hepatic steatosis, liver triglycerides (TG), serum alanine transaminase (ALT) and aspartate aminotransferase (AST), inflammation, and fibrosis in MCDD mice. Interestingly, MCDD led to a significant reduction in IPMK levels, and the deletion of hepatic IPMK exacerbates the NASH phenotype induced by MCDD, accompanied by increased gene expression of pro-inflammatory chemokines. Conversely, TRF restored IPMK levels and significantly reduced gene expression of proinflammatory cytokines and chemokines. Our results demonstrate that TRF attenuates MCDD-induced NASH via IPMK-mediated changes in hepatic steatosis and inflammation.

Indexing serum and mucous biochemical parameters of endangered Chinese sturgeon Acipenser sinensis with implications for health assessment.

The Chinese sturgeon (Acipenser sinensis) is a critically endangered aquatic fish. Health monitoring and welfare assessments are critical for the conservation of Chinese sturgeon. In this study, biochemical parameters of serum and skin mucus in Chinese sturgeon were examined to evaluate the potential biomarkers. Serum and mucous samples were obtained from Chinese sturgeon, and the levels of total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), lactic acid (LD), acid phosphatase (ACP), lysozyme (LYZ), glucose (GLU), and cortisol were determined. The concentrations of ALT, AST, cortisol, and LYZ were significantly higher in the mucous group than those in the serum group (p < 0.05). In addition, the concentrations of ALP, ACP, LD, LDH, CK, and TP were significantly higher level in the serum group than those in the mucous group (p < 0.05). Moreover, the correlations between serum and mucous biochemical parameters were established. Statistical analysis showed a positive correlation between serum and skin mucous markers (ACP, cortisol, and LYZ). AST versus ALT in serum and mucus showed a significant positive correlation (p < 0.01). A significant positive correlation was found between cortisol and CK in mucus (p < 0.01). Moreover, LD versus LDH in serum showed a significant but weak positive correlation (p < 0.01). Principal component analysis revealed a complete separation between the serum and mucous groups, with the biomarkers that contributed the most being ALP, TP, ALT, and AST. This study provides baseline data and reference intervals for serum and mucous biochemical parameters in presumably healthy Chinese sturgeons. The current study has important implications for the development of conservation strategies and the conservation status of critically endangered species.

Genistein relieves liver damage and improves lipid dysregulation through endoplasmic reticulum suppression in nonalcoholic steatohepatitis rats

AbstractIn this study, we investigated the potential of genistein, the most abundant isoflavone in soybeans, to mitigate endoplasmic reticulum (ER) stress in high‐fat high‐sucrose induced nonalcoholic steatohepatitis (NASH) rats. Forty male SD rats are divided into four groups: the Control group, high‐fat high‐sucrose diet group (HFSD), HFSD + low‐dose genistein group (LG), and HFSD + high‐dose genistein group (HG). The Control group is fed with a D12450B diet, whereas the latter three groups are fed with a D12492 diet with 10% sucrose in drinking water. 12 weeks later, serum and liver lipid levels, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and protein expression of GRP78, PKR‐like ER kinase (PERK), p‐PERK, eukaryotic initiation factor (eIF2α), p‐eIF2α and C/EBP homologous protein (CHOP) were characterized. Genistein significantly improved lipid profiles, alleviated AST and ALT levels, and reduced key typical NASH features, including macrovascular steatosis, lobular inflammation, and balloon degeneration of hepatocytes. Furthermore, our results demonstrated that genistein suppressed the activation of PERK‐eIF2α‐CHOP signal pathway induced by HFSD. Our present study indicates that genistein is capable of relieving liver damage, improving lipid dysregulation and modulating ER stress by suppressing the activation of the PERK‐eIF2α‐CHOP signal pathway in NASH rats.Practical Applications: Genistein is capable to relieve liver damage and improve lipid dysregulation through the modulation of PERK–eIF2α–CHOP in NASH rats.

The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats.

This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats. The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2-6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers. Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels). The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.

Flaxseed Lignan Alleviates the Paracetamol-Induced Hepatotoxicity Associated with Regulation of Gut Microbiota and Serum Metabolome.

This study examined the protective effect of flaxseed lignans on liver damage caused by an overdose of paracetamol (PAM). The findings demonstrated that administering 800 mg/kg/d flaxseed lignan prior to PAM significantly decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBi) levels, while it increased liver superoxide dismutase (SOD) and glutathione (GSH) levels in mice. Flaxseed lignan renovated the gut microbiota dysbiosis induced by PAM by promoting the proliferation of sulfonolipid (SL) producing bacteria such as Alistipes and lignan-deglycosolating bacteria such as Ruminococcus while inhibiting the growth of opportunistic pathogen bacteria such as Acinetobacter and Clostridium. Furthermore, flaxseed lignan modulated the serum metabolomic profile after PAM administration, specifically in the taurine and hypotaurine metabolism, phenylalanine metabolism, and pyrimidine metabolism. The study identified eight potential biomarkers, including enterolactone, cervonyl carnitine, acutilobin, and PC (20:3(5Z, 8Z, 11Z)/20:0). Overall, the results suggest that flaxseed lignan can alleviate PAM-induced hepatotoxicity and may be beneficial in preventing drug-induced microbiome and metabolomic disorders.

Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization.

Observational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications. Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses. UVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications. Robust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention.