Lower Serum Alanine Aminotransferase Research Articles

Threonine supplementation stimulates immune, antioxidant and liver functions of largemouth bass, Micropterus salmoides

Threonine is an essential amino acid required in the diets for regular growth of fishes, but information is inadequate regarding the effects of threonine on immunity and health status of many aquaculture species. In the present study, a total of 360 juvenile largemouth bass, Micropterus salmoides (19.0 ± 0.1 g) were divided into six experimental groups, and fed diets supplemented with varying levels of crystalline L-threonine at 0 g kg−1 (control), 2.5 g kg−1 (Thr-2.5), 5.0 g kg−1 (Thr-5.0), 7.5 g kg−1 (Thr-7.5), 10.0 g kg−1 (Thr-10.0) and 12.5 g kg−1 (Thr-12.5) for eight weeks. The results revealed that white blood cell count (P = 0.024) and albumin content (P = 0.006) in fish were significantly modulated by the dietary threonine, with the highest levels recorded in fish fed diets Thr-5.0 and Thr-12.5, respectively. White blood cell increased with dietary threonine levels up to Thr-5.0, then decreased thereafter. The other hematological variables such as red blood cell (P = 0.571), hemoglobin (P = 0.259), hematocrit (P = 0.985), mean corpuscular volume (P = 0.631), mean corpuscular hemoglobin (P = 0.280) and mean corpuscular hemoglobin concentration (P = 0.691) remained unchanged as compared to the control group. Serum lysozyme increased (P = 0.000) with increasing levels of threonine up to 5.0 g kg−1. Fish receiving diet Thr-2.5 had relatively higher (P = 0.000) immunoglobulin M and the level decreased when fed with increasing levels of threonine. The activities of superoxide dismutase (P = 0.008) and malondialdehyde (P = 0.005) were elevated at 10.0 g kg−1 and 12.5 g kg−1 supplementation levels, respectively. Moreover, diets Thr-5.0 and Thr-10.0 induced lower serum alanine aminotransferase (P = 0.011) and aspartate aminotransferase activities (P = 0.000) in fish. These results suggest that threonine supplementation led to a positive effect on the hematology, humoral immunity, antioxidant capacity and liver function enzyme activities of economically important largemouth bass. Therefore, threonine has a clear role in fish nutrition and is important in formulating nutritionally balanced feeds.

Low serum alanine aminotransferase (ALT) levels are associated with poor outcomes in acute ischemic stroke patients regardless of age

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown.This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes.Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11–18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11–22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24–5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05).Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.

A Study on the Protective Impact of Resveratrol on Liver Damage in Rats with Obstructive Jaundice.

Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear. In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways. The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway. In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.

Arbutin ameliorates liver fibrosis in mice by inhibiting macrophage recruitment and regulating the Akt/NF-κB and Smad signaling pathways

To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

FRI037 Time-restricted Feeding Prevents Progression Of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Through IPMK

Abstract Disclosure: I. Jung: None. F. Anokye-Danso: None. S. Jin: None. R.S. Ahima: None. S. Kim: None. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although many clinical trials for NAFLD treatment are undergoing, there are currently no approved therapies. Insulin resistance is central to the progression of NAFLD and implicated in disease progression from steatosis to NASH. Therefore, modulation of insulin resistance represents a potential strategy for NAFLD treatment. We have reported that inositol polyphosphate multikinase (IPMK), a key enzyme in inositol polyphosphate biosynthesis, plays a role in regulating hepatic insulin signaling and gluconeogenesis both in vitro and in vivo. However, the roles of IPMK in hepatic lipid metabolism were not investigated. To determine the role of IPMK in NAFLD/NASH, we fed high fat diet (HFD) or methionine-choline deficient diet (MCDD) in both wild type (WT) and liver-specific IPMK knockout (LKO) mice. We also examined the effect of time-restricted feeding (TRF), which is known to be beneficial for metabolic disease without influencing the food intake, in NAFDL/NASH. Here, we show that hepatic IPMK protein was decreased in WT mice fed a MCDD compared to a normal chow diet (ND) and loss of IPMK in the liver augments hepatic steatosis and steatohepatitis in mice fed a HFD as well as MCDD. Compared to the WT mice, triglycerides (TG) and pro-inflammatory gene expression in the liver increase significantly in the LKO mice fed HFD. Importantly, MCDD-fed LKO mice exhibit exacerbated NAFLD/NASH accompanied by an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic TG accumulation and fibrosis, and pro-inflammatory gene expression. Finally, TRF by limiting a food access only during the dark cycle led to an increase in expression hepatic IPMK protein in MCDD mice. Importantly, TRF alleviates NAFLD/NASH reflected by reduced hepatic TG accumulation, lowered serum ALT and AST levels, downregulated pro-inflammatory gene expression compared with ad libitum mice. Our results demonstrate that loss of IPMK mediates the progression of NAFLD/NASH and may be potentially targeted for treatment of NAFLD/NASH. Presentation: Friday, June 16, 2023

Effects of dietary adjustment of n-3:n-6 fatty-acid ratio to 1:2 on anti-inflammatory and insulin-signaling pathways in ovariectomized mice with high fat diet-induced obesity

Estrogen deficiency increases the secretion of inflammatory mediators and can lead to obesity. Consequently, estrogen deficiency can cause metabolic syndrome, particularly insulin resistance during menopause. Both fish oil and perilla oil contain n-3 fatty acids, which may regulate several inflammatory cytokines. Additionally, adjusting the dietary n-3:n-6 fatty-acid ratio to 1:2 may help treat or prevent chronic diseases. Therefore, we investigated the effect of anti-inflammatory and insulin-signaling pathways, not solely in relation to the (n-3:n-6 fatty-acid ratio at 1:2), but also considering the origin of n-3 fatty acids found in fish oil and perilla oil, in a mouse model of estrogen deficiency induced by ovariectomy and obesity induced by a high-fat diet (HFD). Female C57BL/6J mice were divided into five groups: sham mice on a normal diet; ovariectomized (OVX) mice on a normal diet (OC); OVX mice on a HFD plus lard oil (OL), fish oil (OF), or perilla oil (OP). The dietary n-3:n-6 ratio in the OF and OP groups was adjusted to 1:2. The results showed OF group exhibited significantly lower abdominal adipose tissue weight, fewer liver lipid droplets, and smaller uterine adipocytes, compared with the OL group. Compared with the OL group, the OF and OP groups exhibited higher oral glucose tolerance and lower serum alanine aminotransferase activity, triacylglycerol levels, and total cholesterol levels. Hepatic JAK2, STAT3, and SOCS3 mRNA expression and p–NF–κB p65 and IL-6 levels were significantly lower in the OF and OP groups than in the OL group. Only the OF group exhibited an increase in PI3K and Akt mRNA expression, decrease in GLUT2 mRNA expression, and considerable elevation of p-Akt. Both fish and perilla oil reduced inflammatory signaling markers. However, only fish oil improved insulin signaling (PI3K, Akt, and GLUT2). Our data suggest that fish oil can alleviate insulin signaling through activating the PI3K-Akt-GLUT2 cascade signaling pathway.

GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway.

The common characteristics of alcohol-associated liver injury (ALI) include abnormal liver function, infiltration of inflammatory cells, and generation of oxidative stress. The gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, gastrin-releasing peptide (GRP). GRP/GRPR appears to induce the production of cytokines in immune cells and promotes neutrophil migration. However, the effects of GRP/GRPR in ALI are unknown. We found high GRPR expression in the liver of patients with alcohol-associated steatohepatitis and increased pro-GRP levels in peripheral blood mononuclear cells of these patients compared with that of the control. Increased expression of GRP may be associated with histone H3 lysine 27 acetylation induced by alcohol, which promotes the expression of GRP and then GRPR binding. Grpr-/- and Grprflox/floxLysMCre mice alleviated ethanol-induced liver injury with relieved steatosis, lower serum alanine aminotransferase, aspartate aminotransferase, triglycerides, malondialdehyde, and superoxide dismutase levels, reduced neutrophil influx, and decreased expression and release of inflammatory cytokines and chemokines. Conversely, the overexpression of GRPR showed opposite effects. The pro-inflammatory and oxidative stress roles of GRPR might be dependent on IRF1-mediated Caspase-1 inflammasome and NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified the therapeutic and preventive effects of RH-1402, a novel GRPR antagonist, for ALI. A knockout or antagonist of GRPR during excess alcohol intake could have anti-inflammatory and antioxidative roles, as well as provide a platform for histone modification-based therapy for ALI.

Stronger Neo‐Minophagen C (SNMC): A stronger adjuvant for TACE?

Stronger <scp>Neo‐Minophagen</scp> C (<scp>SNMC</scp>): A stronger adjuvant for <scp>TACE</scp>?

Effects of dietary inclusion of Xanthoceras sorbifolia Bunge leaves on growth performance, gastrointestinal development, digestive function and gut microbial flora of rabbits

This study aimed to investigate the effects of dietary inclusion of Xanthoceras sorbifolia Bunge (X sorbifolia) leaves (XSL) or solid-state fermented X sorbifolia leaves (FXSL) on the growth performance, gastrointestinal tract development, serum metabolites, intestinal mucosa morphology, cecal fermentation and microflora enumeration of rabbits. A total of 192 healthy New Zealand White male rabbits weighing (940 ± 11 g) were randomly allocated to 3 dietary treatments, with 8 replicates of 8 rabbits each and designated as control, XSL, and FXSL groups. The rabbits in the XSL and FXSL groups were fed diets containing 150 g/kg XSL and FXSL in the basal diets to replace the same level of alfalfa hay, respectively for 42 days. Compared with the control or XSL group, the FXSL rabbits showed increased average daily weight gain (P < 0.05) and final body weight, as well as a decreased feed to gain ratio (P < 0.05). They had increased small intestine weight, small intestine relative weight (P < 0.05), cecum weight, cecum relative weight, and decreased urea nitrogen (UN) content (P < 0.05). Rabbits in the XSL and FXSL groups had lower serum alanine aminotransferase (ALT) (P < 0.05) and aspartate aminotransferase (AST) activities, as well as higher serum alkaline phosphatase (AKP) activity (P < 0.05). Compared to the other two groups, the total volatile fatty acids, the ratio of acetic acid, as well as Lactobacilli and Bifidobacterium populations in the cecal content was increased (P < 0.05) in the FXSL group, while the cecal pH, NH3-N, the ratio of butyric acid, Escherichia coli as well as Clostridium perfringens populations were decreased (P < 0.05). Further, the rabbits from the FXSL group showed higher (P < 0.05) villus height (VH) and VH/crypt depth (CD) both in the jejunum and duodenum. In conclusion, adding 150 g/kg XSL to the diet can replace the same amount of alfalfa powder, simultaneously, adding 150 g/kg FXSL can improve the growth and gastrointestinal tract development, as well as the cecal environment and microbiota balance.

An Evaluation of Yeast Culture Supplementation in the Diet of Pseudobagrus ussuriensis: Growth, Antioxidant Activity, Nonspecific Immunity, and Disease Resistance to Aeromonas hydrophila

An 8-week feeding trial was conducted to evaluate the effects of dietary yeast culture (YC) supplementation on growth performance, antioxidant activity, nonspecific immunity, and disease resistance of Pseudobagrus ussuriensis (average initial weight6.01±0.01 g). Four isonitrogenous and isolipidic diets were formulated to contain 0 (Y0), 10 (Y1), 20 (Y2), and 30 (Y3) g/kg YC, respectively. After the feeding experiment, the challenge test of injecting Aeromonas hydrophila was executed. Results showed that appropriate YC supplementation level in the diet could improve growth performance, digestive enzyme activities, nonspecific immunity capacity, antioxidant capacity, and disease resistance of P. ussuriensis. And the highest weight gain, feed intake, specific growth rate, and IGF-1 gene expression level were observed in fish fed the Y2 diet. The activities of protease and amylase in intestine in fish fed the Y2 diet were enhanced compared with that in fish fed the Y0 diet significantly (P&lt;0.05). Simultaneously, fish fed the Y2 diet had significantly higher serum lysozyme activity and significantly lower serum alanine amino transferase activity (P&lt;0.05). Dietary 20 g/kg YC supplementation increased the activity of catalase and total antioxidant capacity in liver and reduced malondialdehyde content in the liver and intestine of P. ussuriensis significantly (P&lt;0.05). Fish fed the Y2 diet had the highest disease resistance under the condition of A. hydrophila challenge (P&lt;0.05). The quadratic regression analysis based on weight gain against dietary YC levels indicated that the appropriate dietary YC supplementation level is 13.4 g/kg diet.

MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis

Lipotoxicity induced by the overload of lipid in the liver, especially excess free cholesterol (FC), has been recognized as one of driving factors in the transition from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). MicroRNA (miR)-379-5p has been reported to play regulatory roles in hepatic triglyceride homeostasis, but the relationship of miR-379-5p and hepatic cholesterol homeostasis has never been touched. In the current study, we found that hepatic miR-379-5p levels were decreased obviously in NAFLD patients and model mice compared with their controls. Moreover, miR-379-5p was discovered to be able to inhibit intracellular FC accumulation and alleviate mitochondrial damage induced by palmitic acid (PA) in vitro. Furthermore, overexpression of miR-379-5p in HFHC-fed db/db mice could reduce the level of hepatic total cholesterol (TC) and FC, and ameliorate hepatic injury reflected by the lower serum alanine aminotransferase (ALT) and aspartate transaminase (AST). Subsequently, by combining spectrometry (MS) and luciferase assay, we identified miR-379-5p suppressed STAT1 through transcriptional and translational regulation. Finally, we confirmed that STAT1 was a transcriptional factor of HMGCS1. In conclusion, miR-379-5p inhibits STAT1 expression and regulates cholesterol metabolism through the STAT1/HMGCS1 axis, suggesting miR-379-5p might be applied to improve lipotoxicity in the future.

Hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4α.

To investigate the relationship between the expression level of hsa-miR-34a-5p and liver injury and to further explore its regulatory signaling pathways Methods: Liver tissue and blood were collected from 60 patients undergoing hepatectomy. We constructed a rat HIRI model and treated it with an intraperitoneal injection of agomir-miR-34a-5p or agomir-normal control (NC) for 7 days after the surgery. The pathological changes of agomir-miR-34a-5p or agomir-normal control (NC) groups were compared. 7702 and AML12 cells were transfected with mimics NC or miR-34a-5p mimics and then treated with H2O2 for 6 hours. Cell apoptosis was detected by flow cytometry, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, respectively. Furthermore, the target genes of miR- 34a-5p were identified by luciferase reporter gene assay and were verified in vitro. The relatively high miR-34a-5p expression group revealed a lower level of alanine aminotransferase and aspartate aminotrans- ferase compared with the relatively low miR-34a-5p expression group. HIRI+agomir-miR-34a-5p rats exhibited significantly higher miR-34a-5p expression, lower serum alanine aminotransferase, aspartate aminotransferase, alleviated hepatic necrosis, reduced hepa- tocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI+agomir-NC rats (P < .05). After hydrogen peroxide treatment, alpha mouse liver-12 cell (AML-12) and normal liver cell line LO2 (LO2) cells transfected with miR-34a-5p mimics had significantly lower apoptosis rate compared with miR-34a-5p mimics NC group (P < .05). Hepatocyte nuclear factor 4α was identified as a miR-34a-5p target gene. Hepatocyte nuclear factor 4α expression was significantly downregulated in AML12 and HL-7702 (7702) cells transfected with miR-34a-5p (P < .05). Moreover, AML12 and 7702 cells transfected with miR-34a-5p signifi- cantly showed higher c-Jun N-terminal kinase (JNK), P38, cleavage cas-3, and BCL2 associated X (Bax) protein levels compared with AML12 and 7702 cells transfected with agomir-NC. miR-34a-5p possibly protected the liver from I/R injury through downregulating Hepatocyte nuclear factor 4α to inhibit the JNK/P38 signaling pathway.

Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials.

The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. Methods: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. Results: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48–14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70–46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = −11.99 (−22.48 to −1.49)). Conclusions: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease.

Hepatocyte Specific gp130 Signalling Underlies APAP Induced Liver Injury.

N-acetyl-p-aminophenol (APAP)-induced liver damage is associated with upregulation of Interleukin-11 (IL11), which is thought to stimulate IL6ST (gp130)-mediated STAT3 activity in hepatocytes, as a compensatory response. However, recent studies have found IL11/IL11RA/gp130 signaling to be hepatotoxic. To investigate further the role of IL11 and gp130 in APAP liver injury, we generated two new mouse strains with conditional knockout (CKO) of either Il11 (CKOIl11) or gp130 (CKOgp130) in adult hepatocytes. Following APAP, as compared to controls, CKOgp130 mice had lesser liver damage with lower serum Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST), greatly reduced serum IL11 levels (90% lower), and lesser centrilobular necrosis. Livers from APAP-injured CKOgp130 mice had lesser ERK, JNK, NOX4 activation and increased markers of regeneration (PCNA, Cyclin D1, Ki67). Experiments were repeated in CKOIl11 mice that, as compared to wild-type mice, had lower APAP-induced ALT/AST, reduced centrilobular necrosis and undetectable IL11 in serum. As seen with CKOgp130 mice, APAP-treated CKOIl11 mice had lesser ERK/JNK/NOX4 activation and greater features of regeneration. Both CKOgp130 and CKOIl11 mice had normal APAP metabolism. After APAP, CKOgp130 and CKOIl11 mice had reduced Il6, Ccl2, Ccl5, Il1β, and Tnfα expression. These studies exclude IL11 upregulation as compensatory and establish autocrine, self-amplifying, gp130-dependent IL11 secretion from damaged hepatocytes as toxic and anti-regenerative.

High Aspartate Aminotransferase/Alanine Aminotransferase Ratio May Be Associated with All-Cause Mortality in the Elderly: A Retrospective Cohort Study Using Artificial Intelligence and Conventional Analysis.

Low serum alanine aminotransferase (ALT) activity and high aspartate aminotransferase (AST)/ALT ratio may be associated with high mortality in the elderly. We aimed to confirm this in an 8-year retrospective cohort study. Clinical data for 5958 people living in a city aged 67–104 years were analyzed for their relationships with all-cause mortality using artificial intelligence (AI) and conventional statistical analysis. In total, 1413 (23.7%) participants died during the study. Auto-AI analysis with five rounds of cross-validation showed that AST/ALT ratio was the third-largest contributor to mortality, following age and sex. Serum albumin concentration and body mass index were the fourth- and fifth-largest contributors. However, when serum ALT and AST were individually considered in the same model, the individual serum ALT and AST activities were the seventh- and tenth-largest contributors. Conventional survival analysis showed that ALT, AST, and AST/ALT ratio as continuous variables were all associated with mortality (adjusted hazard ratios (95% confidence intervals): 0.98 (0.97–0.99), 1.02 (1.02–1.03), and 1.46 (1.32–1.62), respectively; all p < 0.0001). In conclusion, both AI and conventional analysis suggest that of the conventional biochemical markers, high AST/ALT ratio is most closely associated with all-cause mortality in the elderly.

Congxin Lunzhi Fang improves aortic atherosclerosis and regulates ACE2 expression in ApoE-/- mice

To investigate the effect of Congxin Lunzhi Fang (CXLZF) for improving atherosclerosis (AS) and explore its therapeutic mechanism. Thirty ApoE-/- mice were fed on high-fat diet (HFD) to establish AS models, which were randomized equally into model group, low-, medium- and high-dose CXLZF groups (daily dose 4.5, 9, and 18 g/kg, respectively), and simvastatin (5 mg/kg daily) group, with 6 male C57BL/6 mice fed a normal diet as the control group. The mice in the control and model groups were gavaged with normal saline, and those in the treatment groups were gavaged with the indicated drugs for a treatment course of 12 weeks. The changes of atherosclerotic plaque and liver pathologies were observed using oil-red O, HE and Masson staining, and blood lipid profiles and serum levels of glucose, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) of the mice were examined. The protein expressions of ACE2 and E-selectin were determined with Western blotting. Drug-containing serum was collected from SD rats gavaged with CXLZF for treatment of human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL)-induced injury, and the protein expression of ACE2 in the cells was determined. In ApoE-/- mice, CXLZF at all the 3 doses significantly reduced the plaque area and increased the collagen content in atherosclerotic plaque, indicating improved plaque stability. CXLZF treatment, especially at the high dose, also significantly reduced the levels of serum lipids (P < 0.05). CXLZF significantly lowered serum ALT and AST levels, mitigated hepatocyte steatosis (P < 0.05), increased the protein expression of ACE2 and down-regulated E-selectin expression (P < 0.05) in the mice. In HUVEC cultures, CXLZFcontaining serum (5%, 10%, and 20%) significantly up-regulated the cellular expression of ACE2 protein (P < 0.05). CXLZF relieves aortic atherosclerosis in ApoE-/- mice possibly by regulating ACE2 protein.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients in the intensive cardiac care unit

BackgroundFrailty is an underrecognized and important entity that bears worse prognosis. Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. MethodsA retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU)between 1/5/2011 and 1/12/2020 at a single tertiary medical center. ResultsThe study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis, and missing data, followed for a medianduration of 47 months (IQR 20-77).Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 years vs. 65 years, p<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, p< 0.001), had higher rates of comorbiditiesat baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (p< 0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, p = 0.99), long-termmortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, p< 0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46-3). ConclusionsLower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients admitted to the intensive cardiac care unit

Abstract Background Frailty is an under recognized and important entity that bears worse prognosis. Purpose Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. Methods A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU) between 1/5/2011 and 1/12/2020 at a single tertiary medical center. Results The study included 3956 patients after excluding patients with ALT &amp;gt;40 IU/L, cirrhosis and missing data, followed for a median duration of 47 months (IQR 20–77). Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT &amp;gt;10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 vs. 65, P&amp;lt;0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, P&amp;lt;0.001), had higher rates of comorbidities at baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (P&amp;lt;0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, P=0.99), long-term mortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, P&amp;lt;0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46–3). Conclusion Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU. Funding Acknowledgement Type of funding sources: None. 5-year survival according to baseline ALForest plot of variables associated with

Enhanced growth performance, oxidative capacity and immune responses of common carp, Cyprinus carpio fed with Artemisia absinthium extract-supplemented diet

In the present study, the effects of Afsanteen (Artemisia absinthium) aqueous extract (AE) were investigated on growth performance, innate immunity, and oxidative status of common carp, Cyprinus carpio. Common carp juveniles were fed experimental diets that contained 0, 0.5, 1 or 1.5% of AE for 60 days (75 fish/treatment). Thereafter, the fish growth performance, feed efficiency, serum immune-related, biochemical, and antioxidant parameters were determined. The results showed that diets containing 0.5 and 1% of AE enhanced the growth performance and feed efficiency of the fish. Fish fed with AE supplemented diets (at all concentrations) also displayed higher levels of serum lysozyme, alternative complement, total immunoglobulin, superoxide dismutase, and total protein levels compared to the control diet; the highest levels were observed at 1% AE level. Serum albumin levels of all AE-supplemented treatments were significantly higher than the control treatment. Dietary AE supplementation significantly increased plasma glutathione peroxidase activities; the highest value was related to the fish fed 0.5% AE. All AE treatments showed significantly lower serum catalase activities compared to the control; the lowest value was related to 1.5% AE. 0.5 and 1% AE significantly decreased serum malondialdehyde levels. All AE- treated fish exhibited significantly lower serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities; the lowest values were observed in 0.5% or 1% AE. In conclusion, dietary inclusions of AE in juvenile common carp increased growth performance and feed efficiency, improved the innate immunity and antioxidant response, and improved hepatic health. AE at 0.5–1% levels is recommended for common carp diet formulation.

The Ameliorative Effects of Fucoidan in Thioacetaide-Induced Liver Injury in Mice.

Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.