Aspartate Aminotransferase Research Articles

Pharmacotherapeutic potential of pratensein to avert metribuzin instigated hepatotoxicity via regulating TGF-β1, PI3K/Akt, Nrf-2/Keap-1 and NF-κB pathway

Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.

Proanthocyanidins alleviate acute alcohol liver injury by inhibiting pyroptosis via inhibiting the ROS-MLKL-CTSB-NLRP3 pathway

BackgroundAlcoholic Liver Disease (ALD) is a hepatic disorder resulting from prolonged or excessive alcohol intake. The predominant manifestation of ALD is fatty liver, which progresses to alcoholic hepatitis as the disease worsens. Pyroptosis is a novel type of programmed cell death that is intricately linked to the inflammatory cascade, presenting a promising avenue for therapeutic intervention in the management of ALD. Oligomeric proanthocyanidins (OPCs) are polyphenols extracted from grape seeds that have anti-inflammatory and antioxidant properties. However, whether OPCs can treat ALD by suppressing pyroptosis is not completely clarified. PurposeTo explore the role of OPCs in ALD to inhibit pyroptosis and its mechanism. MethodsIn vitro, HepG2 cells were employed to evaluate the beneficial impact of OPCs on alcohol-induced pyroptosis. MTT colorimetric method, enzyme-linked immunosorbent assay (ELISA), western blot (WB), immunofluorescence, acridine orange (AO) staining, and reactive oxygen species (ROS) assay were performed. In vivo, C57BL mice were used and gavaged with alcohol and OPCs. Hematoxylin-eosin staining (HE) staining, alanine aminotransferase (ALT), aspartate aminotransferase (AST) level assay, and WB were performed. ResultsThe findings revealed that OPCs could reduce the alcohol-induced increase in pyroptosis-related proteins, such as pyrin domain-containing 3 protein (NLRP3), cleaved-caspase 1, gasdermin D (GSDMD-N), Interleukin-18 (IL-18), IL-1β (IL-1β). In in vitro mechanistic experiments, We discovered that OPCs ameliorate alcohol-induced pyroptosis by decreasing cathepsin B (CTSB) leakage-mediated NLRP3 activation. More significantly, we discovered that alcohol phosphorylates mixed lineage kinase domain-like protein (MLKL), enabling P-MLKL to translocate to the lysosomal membrane and induce lysosomal membrane permeabilization (LMP). OPCs might counteract the effects of alcohol by reducing the leakage of CTSB and inhibiting the phosphorylation of MLKL through the scavenging of ROS. Conclusions: These results suggested that OPCs might counteract ALD by inhibiting pyroptosis through the ROS-MLKL-CTSB-NLRP3 pathway. Our study offered fresh insight into the ways in which naturally occurring chemicals shield ALD against harm.

Optimizing selenium-enriched yeast supplementation in laying hens: Enhancing egg quality, selenium concentration in eggs, antioxidant defense, and liver health

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

Effects of Transport Stress (Duration and Density) on the Physiological Conditions of Marbled Rockfish (Sebastiscus marmoratus, Cuvier 1829) Juveniles and Water Quality

Live transportation is a critical component of fish farming and hatchery release. To optimize hatchery-release techniques and improve the survival rate of marbled rockfish (Sebastiscus marmoratus, Cuvier 1829) juveniles, the effects of varying transport durations (2, 4, 6, and 8 h) and densities (60, 90, 120, and 150 kg m−3) on the physiological indicators of the fish and water quality were investigated under controlled laboratory conditions. We found that as transport duration and density increased, water quality significantly deteriorated, with ammonia nitrogen levels rising and dissolved oxygen content and pH levels decreasing. Physiological indicators including levels of lactate, cortisol, and malondialdehyde and activities of superoxide dismutase, alkaline phosphatase, and glutamate oxaloacetate transaminase notably increased, indicating that the fish experienced heightened stress during transport. Additionally, the mortality rate of juveniles increased significantly with increasing density and transport duration. The high mortality rate might be associated with sustained elevated cortisol levels and liver damage. Our results are helpful for determining the optimal transport conditions for S. marmoratus juveniles and also provide valuable insights for improving transport techniques for other aquatic animal species.

The hemolysis index as a tool for monitoring mild hemolysis in biochemical assays at the emergency laboratory

Hemolysis is a common pre-analytical error that can affect the accuracy of biochemical assay results. The aim of the study is to investigate the impact of hemolysis on the measurement of nine emergency biochemical parameters: glucose, creatinine, calcium, potassium, sodium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT),total bilirubin, and direct bilirubin. The study included blood samples collected from various units of the maternity hospital, including high-risk pregnancies follow-up, postpartum care, gynecology, neonatology, and intensive care. The study employs a Hemolysis Index (HI) to monitor and assess sample quality, determining their suitability for the analysis of the nine aforementioned biochemical parameters. The results reveal that hemolysis can significantly affect the accuracy of tests results for the studied parameters, particularly for potassium (increased 4-12 times) and AST (increased 1.47-48.55 times). Three of the studied substances showed a significant, negative, and moderate correlation with HI after the osmotic shock was induced, including AST (r = -0.501, p = 0.006), ALT (r = -0.516, p = 0.004), and sodium (r = -0.598, p = 0.001). Conversely, no significant association was found for the other parameters, which are: glucose (r = 0.079, p = 0.639); creatinine (r = 0.140, p = 0.402); direct bilirubin (r = 0.292, p = 0.075); total bilirubin (r = 0.272, p = 0.114); calcium (r = 0.215, p = 0.196); and potassium (r = -0.188, p = 0.258). Our findings indicate that HI may not be helpful for calculating a predicted value for samples with HI ranging between 87.30 and 295.9. Therefore, it is crucial to establish a threshold for the degree of hemolysis beyond which releasing the result would be considered potentially harmful to the patient especially new-borns and premature infants. In conclusion, the appropriate use of HI in clinical laboratories can enhance patient care quality by minimizing the risk of misdiagnosis leading to inappropriate treatment, particularly when requesting a second sample is not feasible.

Safety evaluation of alpha-glycerylphosphorylcholine as a novel food

To evaluate the safety of alpha-glycerylphosphorylcholine (α-GPC) as a novel food, the study of acute oral toxicity, subchronic toxicity, teratogenic toxicity and genotoxicity were conducted. In acute oral toxicity, no toxic effects were observed in rats of both genders administrated 10.0 g/kg BW α-GPC. In 90-day oral toxicity, female high-dose group (2,000 mg/kg) had lower body weight, body weight gain, empty stomach body weight, total protein (TP), albumin (ALB), and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in contrast to control group. In teratogenic toxicity, the body weights of pregnant rats on the 9th day (d9), the 12th day (d12), the 15th day (d15), and the 20th day (d20), body weight gains, and net body weight gains in high-dose group (2,000 mg/kg) decreased, the other parameters had no difference compared to control group. In genotoxicity tests (Mammalian erythrocyte micronucleus, Chromosome aberration and Ames test), all dose groups didn't display significant change compared with negative control group. Based on above results, α-GPC is actually low hazard novel food, has a NOAEL of 1,000 mg/kg BW for female rats and 2,000 mg/kg BW for male rats following 13-week oral exposure, has a NOAEL of 1,000 mg/kg BW for pregnant rats and 2,000 mg/kg BW for fetal rats in teratogenic toxicity, has no genotoxicity in vitro or in vivo.

KRAS-G12 inhibitors in lung cancer therapy: unveiling the toxicity profile through a pharmacovigilance study.

With the advent of drugs designed to selectively target the KRAS-G12C mutant protein, sotorasib and adagrasib have exhibited remarkable efficacy in patients with KRAS G12C mutant lung cancers. Nevertheless, the safety profiles of these agents in a real-world context remain undisclosed. Data was systematically extracted from the FDA Adverse Event Reporting System (FAERS) website from January 2021 to December 2023, focusing on adverse events associated with KRAS G12C inhibitors, sotorasib and adagrasib. The predominant adverse events attributed to KRAS G12C inhibitors predominantly encompassed general disorders and administration site conditions, investigations, and gastrointestinal disorders. Among these, the significant adagrasib-related adverse events comprised nausea, diarrhea, vomiting, asthenia, dizziness, and weight loss. Notably, incidences of renal failure were also documented in patients receiving adagrasib. Conversely, the primary adverse events associated with sotorasib included diarrhea, nausea, abnormal hepatic function, elevated levels of aspartate aminotransferase and alanine aminotransferase, and hepatotoxicity. It is noteworthy that a considerable number of adverse events manifested within the inaugural month following the initiation of therapy with KRAS G12C inhibitors. Although most adverse effects are reversible, vigilance is warranted particularly for nephrotoxicity and hepatotoxicity during the administration of KRAS G12C inhibitors.

Interventional effect of bone marrow mesenchymal stem cell transplantation with different doses of X-ray irradiation induced hepatic injury in mice

Objective: To investigate the interventional effect of bone marrow mesenchymal stem cell (BMMSC) transplantation with different doses of X-ray irradiation induced hepatic injury in mice. Methods: Eighteen female C57BL/6J mice were randomly divided into 0, 2, and 3 Gy irradiation groups and 0, 2, and 3 Gy transplantation groups. The irradiation group was used as the control and injected with an equal volume of culture medium. The mice in the transplantation group were irradiated with different doses of X-ray irradiation, and BMMSCs were intravenously infused into the bone marrow. The mice were sacrificed for sampling at the end of the 21st day. Mice body weight changes were recorded daily. The changes in the content of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were detected by an automatic blood tester. The morphological changes in mice liver tissues were observed by hematoxylin-eosin staining. The serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by a biochemical analyzer. The reduced glutathione contents in liver tissue were detected by the microplate method. The malondialdehyde content in liver tissue was detected by thiobarbituric acid. The content of total superoxide dismutase (T-SOD) in liver tissue was detected by the hydroxylamine method. The expression of the F4/80 protein in liver tissue was detected by the immunohistochemistry method. The protein expression of nuclear transcription factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in liver tissue was determined by the western blotting method. The mRNA expression of NLRP3, IL-6, and Nrf2 in liver tissue was detected by a real-time quantitative polymerase chain reaction. The multiple-group comparisons were analyzed by factorial analysis of variance. The inter-group comparisons were analyzed by the LSD method for statistical analysis. Results: The contents of peripheral blood lymphocytes, erythrocytes, platelets, and hemoglobin were significantly decreased in the 3 Gy irradiation group than the 0 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly increased (P<0.05). The malondialdehyde content, F4/80 protein expression level, nucleotide-binding domain and leucine-rich repeats, nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), and interleukin 6 mRNA expression levels were significantly increased in liver tissue, while the contents of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly decreased (P<0.05). The contents of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were significantly increased in the 3 Gy transplantation group than the 3 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly decreased (P<0.05). The malondialdehyde content, F4/80 protein expression level, NLRP3 and interleukin-6 mRNA expression levels in liver tissue were significantly decreased (P<0.05), while the content of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly increased (P<0.05). Conclusion: X-ray irradiation at a dose of 3 Gy can induce liver oxidative damage in mice. BMMSC transplantation can improve X-ray irradiation-induced liver oxidative damage in mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1 pathway.

Analysis of the clinical characteristics of HBeAg-negative chronic HBV infection in indeterminate phase with a low viral load

Objective: To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load. Methods: One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group (n=59) and high HBsAg group (n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results: There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion: The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

The Role of Hyperemesis Gravidarum in the First-Trimester as a Predictor of Intrahepatic Cholestasis of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) and hyperemesis gravidarum (HEG) are pregnancy-specific liver diseases associated with significant fetal and maternal complications. Typically, HEG is diagnosed in the first trimester of pregnancy, and ICP in the third trimester of pregnancy. The aim of this study is to investigate whether primigravid women diagnosed with ICP between the 26th and 37th weeks of pregnancy were also diagnosed with HEG during the first trimester, and to evaluate whether the diagnosis of ICP can be predicted in pregnant women with a prior diagnosis of HEG. Methods: Our study is a retrospective analysis. A total of 4000 pregnant women, aged 18 to 45 years and between 26th and 37th weeks of gestation, who presented to the Gynecology and Obstetrics Clinic of the Health Sciences University, Istanbul Training and Research Hospital with complaints of pruritus between 01/07/2018 and 01/07/2023, were screened. 227 patients were diagnosed with ICP. Complete medical records and blood test results were available for 141 patients. 39 patients with a history of previous pregnancies and/or comorbidities, as well as 30 patients without available serum total bile acids (TBA) results, were excluded from the study. Of these, 72 pregnant women who met the inclusion criteria were enrolled in the study and grouped into primigravid women with and without a history of HEG in the first-trimester. Demographic characteristics, gestational age, detailed medical history, ultrasound findings, and biochemical parameters—including alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, and fasting bile acid (FBA) levels were statistically compared. Results: In our study, comparisons revealed no significant differences in AST, ALT, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and direct bilirubin levels (p &gt; 0.05) between the groups with and without a history of HEG diagnosed with cholestasis. In pregnant women diagnosed with cholestasis, the total bilirubin and indirect bilirubin levels were significantly lower (p &lt; 0.05) in the group with a history of HEG compared to the group without a history of HEG. In contrast, TBA levels were significantly higher (p &lt; 0.05) in the group with a history of HEG compared to the group without a history of HEG. Conclusions: This study found that primigravid women with ICP and a history of HEG had elevated TBA levels, while total and indirect bilirubin levels were reduced. This suggests that patients with a history of HEG should be closely monitored in later stages of pregnancy for the development of ICP and potential liver damage. However, larger and more comprehensive studies are needed to confirm these findings.

Ameliorative Effects of Pearl Millet (Pennisetum glaucum L.) Against Hydrogen Peroxide Induced Cognitive Impairment and Oxidative Stress in Rats.

Pearl millet (PM) (Pennisetum glaucum L.) contains a wide variety of bioactive compounds, such as polyphenols, mostly flavonoids and phenolic acids. In the present study, we investigated the effects of PM activity against hydrogen peroxide (H2O2)-induced behavior impairment and oxidative damage in rats. The rats were divided into four groups based on the treatments they received over 30 days: Control, H2O2, PM + H2O2, and PM. The phytochemical screening, total polyphenols content (TFC), and total flavonoid content (TFC) were determined using colorimetric analysis. All animals were subjected to behavioral test (elevated plus maze test). Thereafter, oxidative stress response (malondialdehyde [MDA], H2O2, and Thiol groups [-SH]) contents and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) were estimated in brain, liver, and kidney tissues. We evaluated the levels of liver enzymes, such as alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT). Our investigation showed that PM is rich in total phenolic content and TFC and exhibited an important in vitro antioxidant activity. In vivo, we first found that H2O2-treated rat exhibited anxiogenic behavior in the elevated plus maze test and the genesis of oxidative stress in the brain, liver, and kidney was measured by an increase of MDA and antioxidant enzyme activity depletion, such as SOD and CAT. Moreover, H2O2 increased levels of liver enzymes (ALAT and ASAT). Pearl Mille administration improved emotional behavior impairments and significantly reversed H2O2-induced biochemical alterations. Thus, we suggest that the Pearl Mille may have an anxiolytic-like effect and prevent biochemical disorders associated from the oxidative stress (H2O2), confirming its potential therapeutic capability.

Integrated multi-omics analyses combined with western blotting discovered that cis-TSG alleviated liver injury via modulating lipid metabolism.

Background: Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model. Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress. Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.

Intraperitoneal and Extraperitoneal Pringle Hepatic Hilar Occlusion in Laparoscopic Liver Resection: A Prospective Randomized Controlled Study.

This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection. From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices. There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group. IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster.

Zebrafish Larvae as a Predictive Model for the Risk of Chemical-Induced Cholestasis: Phenotypic Evaluation and Nomogram Formation.

Chemical-induced cholestasis (CIC) has become a concern in chemical safety risk assessment in pharmaceutical, food, cosmetic, and industrial manufacturing. Currently, known animal and in vitro liver models are unsuitable as high-throughput screening tools due to their high cost, time-consuming, or poor screening accuracy. Herein, a cohort of chemicals validated as cholestatic hepatotoxic in humans, rodents, and in vitro liver models was established for testing. The accuracy and reliability of the detection of CIC in zebrafish larvae were assessed by liver phenotype, bile flow inhibition rate, bile acid distribution, biochemical indices, and RT-qPCR. In addition, the nomogram prediction model was constructed using binomial logistic regression analysis. The model was constructed with three variables: aspartate aminotransferase (AST.FC) level, total bile acid (TBA.FC) level, and fold change in the number of bile acid nodes per unit of bile ducts in the zebrafish liver (NPL.FC), which showed high predictive power (areas under the ROC curve: 0.983). Furthermore, this study demonstrated that zebrafish larvae have some model specificity for CIC risk assessment of estrogen endocrine disruptors and that testing after 10 dpf provides more scientific results. Overall, combining zebrafish larval phenotyping and nomograms is an efficient and powerful tool for CIC risk monitoring of chemicals.

Effect of the Lactation Phases on the Amplitude of Variation in Blood Serum Steroid Hormones and Some Hematochemical Analytes in Three Dairy Cow Breeds.

Lactation in dairy cows implies comprehensive endocrine and metabolic changes including a systemic electrolytic reaction. Previous studies have rarely considered these specific demands due to the influence of lactation periods. Therefore, this study aimed to assess the effects of early, middle, and late lactation phases on the dynamic changes in serum concentrations of progesterone (P4), 17β-oestradiol (E2), cortisol, and some electrolytes (Ca++, Mg++, Na+, K+, Cl-, Pi) and biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), total bilirubin, urea, and iron (Fe++) in 10 Holstein, 10 Brown Swiss, and 10 Modicana multiparous healthy dairy cows (4.2 ± 1.7 years of age) sampled at 60-day intervals throughout lactation. Lactation induced significant changes in the concentrations of P4, which peaked at >120-180 days, decreased at >240-300 days, and increased again after 300 days. Cortisol showed an opposite trend to P4, with concentrations progressively decreasing, except for the phase between >240 and 300 days, and a steep drop at >300 days compared to previous phases. Na+ concentrations showed the lowest values at 0-60 d and the highest ones at >180-240 days, whereas Mg++ showed the highest values at >60-120 d and the lowest at >300 d. Significant correlations were found between P4 with cortisol, Cl- and K+, and cortisol with Ca++ and LDH. Significant differences in average concentrations of AST, ALT, LDH, Ca++, Mg++, and Fe++ were observed among different dairy cow breeds. Understanding the dynamic changes in hormone levels, electrolytes, and biochemical parameters during different lactation phases, while considering breed differences in dairy cows, is crucial for improving herd health management and milk production in commercial dairy farms.

Protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice

Objective: To explore the protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice. Methods: In June 2023, 42 healthy SPF male Kunming mice were selected. The mice were divided into blank control group, model (0.45 mg/kg α-amanitin) group, olive oil (10 ml/kg olive oil) group, low dose (20 mg/kg) astaxanthin group, medium dose (40 mg/kg) astaxanthin group, high dose (80 mg/kg) astaxanthin group and silybin (20 mg/kg) group by random number table method. Each group had 6 animals. Mice in the blank control group were intraperitoneally injected with 10 ml/kg normal saline, and mice in the other group were injected with α-amanitin. After that, the blank control group and model group were infused with 10 ml/kg normal saline, olive oil group and astaxanthin groups were given olive oil and astaxanthin according to dose by gavage, and silybin group was injected with silybin by dose. The drug was administered once every 12 h for a total of 4 doses. After 60 h, the mice were killed, the liver weight was weighed, and the liver index was calculated. The contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of mice were detected, and the contents of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA) in liver tissues were also detected. One-way analysis of variance (ANOVA) was used to compare the difference of indexes among each group, and pairwise comparison was performed by Dunnett-t test. Results: The mice in the blank control group had smooth hair color, good spirit and normal behavior, while the mice in the other groups showed varying degrees of retardation and decreased diet, and no death occurred in each group. Body mass[ (26.67±1.51) g] and liver mass[ (1.23±0.14) g] in model group were significantly lower than those in blank control group [ (33.50±2.43) g and (1.87±0.16) g], and the differences were statistically significant (P<0.05). The liver index [ (5.39±0.32) %, (5.83±0.30) %, (5.75±0.24) % and (5.78±0.16) %] in low, medium and high dose astaxanthin groups and silybin group were significantly higher than those in model group [ (4.61±0.12) %], and the differences were statistically significant (P<0.05). Serum ALT and AST contents in model group [ (153.04±13.96) U/L and (59.08±4.03) U/L] were significantly higher than those in blank control group [ (13.77±1.29) U/L and (10.21±0.35) U/L], and the differences were statistically significant (P<0.05). The contents of CAT, GSH and SOD in liver tissues of model group [ (9.40±2.23) U/mgprot, (3.09±0.26) μmol/gprot and (48.94±3.13) U/mgprot] were significantly lower than those of blank control group [ (26.36±2.92) U/mgprot, (6.76±0.71) μmol/gprot and (89.89±4.17) U/mgprot], the differences were statistically significant (P<0.05). MDA content[ (6.33±0.24) nmol/mgprot] in liver tissue of model group was significantly higher than that of blank control group [ (0.91±0.21) nmol/mgprot], and the difference was statistically significant (P<0.05). The CAT contents[ (18.64±1.76) U/mgprot, (18.20±1.76) U/mgprot, and (15.54±1.36) U/mgprot] in liver tissues of low, medium and high dose astaxanthin groups were significantly higher than those of model group, with statistical significances (P<0.05). Compared with model group, SOD contents[ (72.16±7.44) U/mgprot, (93.18±5.28) U/mgprot, (103.78±7.07) U/mgprot, and (96.60±7.02) U/mgprot] in liver tissues of mice in low, medium and high dose astaxanthin groups and silybin group were significantly increased (P<0.05), MDA contents [ (4.30±0.84) U/mgprot, (3.66±0.28) U/mgprot, (2.96±0.29) U/mgprot, and (2.88±0.39) U/mgprot] were significantly decreased (P<0.05). Compared with model group, GSH content [ (7.90±1.25) μmol/gprot] in high dose astaxanthin group was significantly increased (P<0.05) . Conclusion: Astaxanthin may alleviate acute liver injury induced by α-amanitin by alleviating oxidative stress in mice liver.

Application of Intraoperative Ultrasound in Laparoscopic Liver Resection with Pringle Maneuver: A Comparative Study with the Pringle Maneuver.

Background: Appropriate surgical techniques for controlling bleeding and preserving residual liver function are key to the success of laparoscopic liver resection. This study aims to evaluate the application effect of intraoperative ultrasound in the Pringle maneuver of laparoscopic liver resection. Materials and Methods: Between January 2022 and June 2023, 100 patients underwent laparoscopic liver resection and were randomly allocated to receive application of intraoperative ultrasound for Pringle maneuver (intraoperative ultrasound group, n = 50) or conventional Pringle maneuver (conventional group, n = 50). Intraoperative blood loss, blood transfusion, operation time, hepatic portal block time, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failure), and hospital stay were compared between groups, along with the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at postoperative days 1, 3, and 7. Results: The operation time, postoperative ALT, AST, and TB levels on postoperative days 1, 3, and 7, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failures), and hospital stay were comparable between groups. Compared with the conventional group, the intraoperative ultrasound group had significantly less intraoperative blood loss (P = .015), lower blood transfusion rate (P = .035), and less hepatic portal block time (P = .012). Conclusions: Applying intraoperative ultrasound in laparoscopic liver resection for hepatic pedicle occlusion is a safe, simple, and effective method.

Huazhi Rougan Granule Alleviates Liver and Intestinal Damage in Non-Alcoholic Fatty Liver Disease by Regulating miR-122 Expression and TLR4/MyD88/NF-κB Pathway Activation.

miR-122 is upregulated in non-alcoholic fatty liver disease (NAFLD) liver tissue, and knockdown of miR-122 protects hepatocytes from lipid metabolism disorders. This study aimed to investigate whether Huazhi Rougan Granule (HRG) alleviates NAFLD liver and intestinal injury by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway. Rats with NAFLD were constructed by high-fat feeding. Serum levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using a fully automated biochemical instrument. Histopathological changes in the liver and small intestine were observed by HE staining. QRT-PCR detected the expression level of miR-122 in the liver tissues. The protein expression of TLR4, MyD88, NF- κB p65, and p-p65 in liver tissues was detected by western blotting. HRG slowed down the weight gain of NAFLD rats, decreased (P<0.05) the levels of TC, TG, ALT, AST, TNF-α, IL-1β, IL-6, LPS, and Hpt, improved the pathological status of liver and small intestine tissues, upregulated (P<0.05) the expression of ZO-1 and Occludin, downregulated (P<0.05) the protein expression of TLR4, MyD88, and p-p65, and inhibited (P<0.05) the expression of miR-122. HRG may alleviate hepatic and intestinal injuries in rats with NAFLD by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?

Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient's autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin-bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.