Serum Alanine Aminotransferase Levels Research Articles

Serum Metabolomics Uncovers the Mechanisms of Inulin in Preventing Non-Alcoholic Fatty Liver Disease.

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD.

Does curcumin improve liver enzymes levels in nonalcoholic fatty liver disease? A systematic review, meta-analysis, and meta-regression.

The aim of this meta-analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random-effects models with DerSimonian-Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD.

Cell-type-specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B.

Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi-omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population-specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon-stimulated genes (ISGs). Validation through multi-immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune-negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi-omics analysis integrating bulk transcriptomic, single-cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

Effect of Orchidectomy on Hepatic Ischemia/Reperfusion Injury

Abstract Background Little attention has been paid to investigate the effect of orchidectomy on hepatic ischemia/reperfusion (I/R) injury, which is lacking. The Aim of This Study is to evaluate the possible impact of orchidectomy and/or testosterone treatment on the function and structure of liver in rat model of hepatic I/R injury and, also, to explore the possible underlying mechanism(s). Materials and Methods 65 male Wistar albino-rats were divided into 5 groups; sham- operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone- treated hepatic ischemia/reperfusion group (T+I/R) and Orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α) and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. Results Hepatic I/R was associated with significant rise of serum ALT and AST, and hepatic tissue TNF-α, NF-κB and MDA, and significant reduction of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2. Histopathological analysis showed vacuolization of the cytoplasm, dilated sinusoids, inflammatory cells infiltration, increased collagen fibers and significantly increased caspase-3. Hepatic I/R -mediated effects were aggravated following orchidectomy, however preischemic treatment with testosterone protected the liver as shown by the significant decline in ALT and AST, and hepatic tissue MDA, TNF-α and NF-κB, and significant enhancement of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2, and restoration of hepatic architecture. Conclusion Orchidectomy hypersensitizes the liver to ischemic injury, due to exaggeration of oxidative and inflammatory states and apoptosis, while testosterone treatment improved the hepatic I/R detrimental effects on liver function and morphology due to its suppressive effect on oxidative and inflammatory states and apoptosis.

The cytochrome P4501A1 (CYP1A1) inhibitor bergamottin enhances host tolerance to multidrug-resistant Vibrio vulnificus infection

PurposeVibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. MethodsAn increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. ResultsIn mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). ConclusionBergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer

RNA splicing regulation has revolutionized the treatment of challenging diseases. Neuroendocrine cancers, including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (PCa), are highly aggressive, with metastatic neuroendocrine phenotypes, leading to poor patient outcomes. We investigated amido-bridged nucleic acid (AmNA)-based splice-switching oligonucleotides (SSOs) targeting RE1-silencing transcription factor (REST) splicing as a novel therapy. We designed AmNA-based SSOs to alter REST splicing. Tumor xenografts were generated by subcutaneously implanting SCLC or PCa cells into mice. SSOs or saline were intraperitoneally administered and tumor growth was monitored. Blood samples were collected from mice after SSO administration, and serum alanine aminotransferase and aspartate aminotransferase levels were measured to assess hepatotoxicity using a biochemical analyser.Invitro, REST_SSO reduced cancer cell viability. In a tumor xenograft model, it exhibited significant antitumor effects. It repressed REST-controlled RE1-harboring genes and upregulated miR-4516, an SCLC biomarker. Our findings suggest that REST_SSO suppresses tumorigenesis in neuroendocrine cancers by restoring REST function. This novel therapeutic approach holds promise for intractable neuroendocrine cancers such as SCLC and neuroendocrine PCa.

Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

Objective: To explore the effect of black radish (Raphanus sativus L. var niger) root extract on liver enzymes, oxidative stress, and histopathological alterations in mice with sodium valproate-induced hepatotoxicity. Methods: Thirty-two mice were divided into four groups: the control group received drinking water by gavage, the second group was administered with 100 mg/kg of sodium valproate, the third group received 300 mg/kg of black radish root extract, and the fourth group was given both sodium valproate (100 mg/kg) and black radish root extract (300 mg/kg). After 28 days, the mice were euthanized, and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), along with liver malondialdehyde (MDA), reactive oxygen species (ROS), mitochondrial parameters, tumor necrosis factor-alpha (TNF-α) gene expression, and histopathological changes were assessed. Results: Sodium valproate caused hepatic damage in mice, characterized by elevated serum levels of liver enzymes, increased MDA and ROS levels and TNF-α gene expression, as well as histopathological alterations. The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST, MDA, ROS, TNF-α gene expression, as well as mitochondrial impairment, but did not have a significant effect on sodium valproate-induced histopathological changes. Conclusions: The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury, possibly through mitigating oxidative stress, mitochondrial impairment, and inflammatory mediator expression.

Microbial creation of β-Nicotinamide mononucleotide and its regulation of lipid metabolism in the liver of high-fat diet mice.

β-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide adenine dinucleotide (NAD+). To determine the safety and biological activity of NMN resources, we constructed a recombinant strain of P. pastoris that heterologously expresses nicotinamide-phosphate ribosyltransferase (NAMPT), and subsequently catalyzed and purified the expressed product to obtain NMN. Consequently, this study established a high-fat diet (HFD) obese model to investigate the lipid-lowering activity of NMN. The findings showed that NMN supplementation directly increased the NAD+ levels, and reduced HFD-induced liver injury and lipid deposition. NMN treatment significantly decreased total cholesterol (TC) and triglyceride (TG) in serum and liver, as well as alanine aminotransferase (ALT) and insulin levels in serum (p < .05 or p < .01). In conclusion, this study combined synthetic biology with nutritional evaluation to confirm that P. pastoris-generated NMN modulated lipid metabolism in HFD mice, offering a theoretical framework and evidence for the application of microbially created NMN.

Inhibition of FoxO1 ameliorates hepatic steatosis and hepatitis in nonalcoholic steatohepatitis mice through regulation of gut microbiota.

We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms. Mice were given methionine-choline-sufficient (MCS), or methionine- and choline-deficient (MCD) diet for 5 weeks, along with AS (60 mg/kg) or vehicle gavage treatment (0.2 mL/day). Body and liver weight, serum triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose and insulin levels were measured. Liver macrophage infiltration and ileal ZO-1 protein expression were also detected. Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, sterol regulatory element binding protein (SREBP)-1c, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase), α-smooth muscle actin (SMA), recombinant collagen type III α1 (Col3a1), and connective tissue growth factor (Ctgf) expressions were measured. Stool samples were collected for 16S rDNA sequencing. Compared to the MCD group, AS attenuated liver weight, reduced serum TG, ALT, and AST levels, increased HDL-C levels, mitigated hepatic steatosis, decreased macrophage infiltration, and augmented ileal ZO-1 proteins in NASH mice. It also reduced the levels of IL-6, IL-1β, and TNF-α, alongside with the Srebp-1c mRNA expression. However, no significant effects on Pepck, G6Pase, α-SMA, Col3a1, or Ctgf were observed. Furthermore, AS promoted diversity and altered gut microbiota composition in NASH mice, causing increased beneficial bacteria like Akkermansia muciniphila, Parabacteroides distasonis, and Prevotellamassilia, which were associated with metabolic functions. FoxO1 inhibitor AS ameliorated hepatic steatosis, inflammation, and intestinal dysbiosis in NASH mice, making it a potentially promising treatment for NASH.

A novel phosphodiesterase inhibitor for the treatment of chronic liver injury and metabolic diseases.

Chronic liver disease (CLD) leads to approximately two million deaths annually. Cyclic adenosine monophosphate (cAMP) signaling has long been studied in liver injury, particularly in the regulation of fatty acid (FA) β-oxidation and pro-inflammatory polarization of tissue-resident lymphocytes. Phosphodiesterase 4B (PDE4B) inhibition has been explored as a therapeutic modality, but these drugs have had limited success and are known to cause significant adverse effects. The PDE4 inhibitor 2-(4-([2-(5-Chlorothiophen-2-yl)-5-ethyl-6-methylpyrimidin-4-yl]amino)phenyl)acetic acid) (known as A-33) has yet to be explored for the treatment of metabolic diseases. Herein, we evaluated the efficacy of A-33 in the treatment of animal models of alcohol-associated liver disease (ALD) and steatotic liver disease (SLD). We demonstrated that A-33 effectively ameliorated the signs and symptoms of CLD, resulting in significant decreases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, decreased overall fat and collagen deposition in the liver, decreased intrahepatic triglyceride (TG) concentrations, and normalized expression of genes related to β-oxidation of fatty acids, inflammation, and extracellular matrix (ECM) deposition. We also designed and synthesized a novel analog of A-33, termed MDL3, which inhibited both PDE4B and PDE5A and was more effective in ameliorating pathophysiological signs and symptoms of liver injury and inflammation. In addition, MDL3 re-sensitized obese mice to glucose and significantly inhibited the pathological remodeling of adipose tissue, which was not observed with A-33 administration. In conclusion, we synthesized and demonstrated that MDL3, a novel PDE4B and PDE5A inhibitor, presents a promising avenue of exploration for treating CLD.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic liver disease (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Metabolic Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and age independently predict ALT levels among blood donors. Over the last few decades, the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges. With this backset, Chen et al have recently published a study which has two main findings. First, &gt; 80% of individuals with MAFLD had normal ALT levels. Second, there was a linear increasing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD. This study has biologically credible findings. However, it inaccurately considered sex differences in the MAFLD arena. Therefore, future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Cohort Study

ObjectivesTo assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. Study designIn this prospective, cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4 to 6 months, anthropometric measurements, serum biochemical analysis, ultrasound and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration and hepatic IR by the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. Results56% of 200 patients with obesity had evidence of steatosis on ultrasound and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already elevated in patients with only mild steatosis (p = 0.0403). Patients with more insulin-sensitive adipose tissue exhibited lower liver fat content (p < 0.05) and serum alanine transaminase levels (p = 0.001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (p < 0.001), but not with total body fat percentage (p = 0.263). After 4 to 6 months of lifestyle management, both MASLD and Adipo-IR improved. ConclusionsOur data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

Prevalence, characteristics, and risk factors of non-alcoholic fatty liver disease in North East of Iran: a population-based study

BackgroundNonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The present study aimed to investigate the prevalence, characteristics, and risk factors of NAFLD in the Mashhad Persian Cohort Study population.MethodThe present population-based cross-sectional study included all PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences (POCM), Mashhad, Iran by census sampling method. Eligible participants were divided into two groups due to their NAFLD condition (NAFLD positive or NAFLD negative). All enrolled participants were evaluated based on their clinical aspects, anthropometric measures, laboratory tests, and ultrasound features. Statistical analysis was conducted using SPSS software version 16 (SPSS Inc., Chicago, USA –version 16). A P-value less than 0.05 was considered as the significance level.ResultsA total of 1198 individuals were included in the study, of which 638 (53.3%) were male and the rest were female. The mean age of the participants was 46.89 ± 8.98 years. A total of 246 patients (20.53%) were NAFLD positive, of which 122 (49.59%) were in grade 1, 112 (45.52%) were in grade 2, and 12 (4.87%) were in grade 3. The prevalence of fatty liver was significantly higher in males than in females (p < 0.001). There were significant differences between NAFLD positive and NAFLD negative participants in terms of having a history of hypertension (P = 0.044), body mass index (P < 0.001), body fat percentage (P = 0.001), waist circumference (P < 0.001), liver craniocaudal length (P = 0.012), fasting blood sugar (FBS) (P = 0.047), aspartate aminotransferase (AST) (P = 0.007), and alanine aminotransferase (ALT) (P = 0.001). Further analysis revealed a strong significant association between BMI, previous history of hypertension, higher levels of serum ALT, and NAFLD (P < 0.05).ConclusionIt can be concluded that ultrasound findings accompanied by laboratory AST and ALT level enzymes could be a cost-benefit approach for NAFLD early diagnosis. The craniocaudal size of the liver could be a beneficent marker for estimating the severity of the disease; however, more studies are recommended to evaluate this variable for future practice against the issue.

Icaritin attenuates ischemia–reperfusion injury by anti-inflammation, anti-oxidative stress, and anti-autophagy in mouse liver

BackgroundHepatic ischemia–reperfusion (IR) injury is a major complication of liver transplantation and gravely affects patient prognosis. Icaritin (ICT), the primary plasma metabolite of icariin (ICA), plays a critical role in anti-inflammatory and immunomodulatory processes. However, the role of ICT in hepatic IR injury remains largely undefined. In this study, we aimed to elucidate the role of ICT in hepatic IR injury. MethodsWe established hepatic IR injury models in animals, as well as an oxygen-glucose deprivation/reperfusion (OGD/R) cell model. Liver injury in vivo was assessed by measuring serum alanine aminotransferase (ALT) levels, necrotic areas by liver histology and local hepatic inflammatory responses. For in vitro analyses, we implemented flow-cytometric and western blot analyses, transmission electron microscopy, and an mRFP-GFP-LC3 adenovirus reporter assay to assess the effects of ICT on OGD/R injury in AML12 and THLE-2 cell lines. Signaling pathways were explored in vitro and in vivo to identify possible mechanisms underlying ICT action in hepatic IR injury. ResultsCompared to the mouse model group, ICT preconditioning considerably protected the liver against IR stress, and diminished the levels of necrosis/apoptosis and inflammation-related cytokines. In additional studies, ICT treatment dramatically boosted the expression ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR proteins in hepatic cells following OGD/R damage. We also applied LY294002 (a PI3K inhibitor) and RAPA (rapamycin, an mTOR inhibitor), which blocked the protective effects of ICT in hepatocytes subjected to OGD/R. ConclusionThis study indicates that ICT attenuates ischemia–reperfusion injury by exerting anti-inflammation, anti-oxidative stress, and anti-autophagy effects, as demonstrated in mouse livers. We thus posit that ICT could have therapeutic potential for the treatment of hepatic IR injury.

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.

Immediate Effects of Anesthesia Agents on Liver Function

Anesthetic agents and types may deteriorate liver function; therefore, choosing anesthetics with less hepatotoxicity is important. The elevations of serum aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels are frequently observed after surgical procedures, whether performed under general or spinal (regional) anesthesia. Therefore, the study aimed to investigate and compare the changes in liver enzymes following general anesthesia and regional anesthesia. An observational sheet was used to obtain data from patients and then statistically analyzed using the IMB Statistical Package for Social Sciences (SPSS) Statistic software version (23). A significant difference in the liver enzymes levels change was determined with a p-value of &lt; 0.05. it was observed that in both groups of general and regional anesthesia, the level of AST, ALT, and ALP enzymes was significantly elevated post-operative compared to pre-operative with (P=0.000), especially in the level of ALT enzyme. The current study indicated that both general and regional anesthesia caused increased liver enzymes.

Analysis of serum ascites albumin gradient (SAAG) in cats with hepatic disorder

Three Persian breed cats were diagnosed to be having hepatitis. Clinical examination revealed dullness, dehydration, poor body condition and fluid thrill on the abdominal palpation. Radiography and ultrasonography revealed ground glass appearance of the abdomen and anechoic fluid in the abdomen respectively. Elevated serum ascites albumin gradient with elevated serum alanine transaminase levels were noticed in these cats

Clinical and virological characteristics of coexistent hepatitis B surface antigen and antibody in treatment-naive children with chronic hepatitis B virus infection.

Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.

Effect of smartphone-assisted lifestyle intervention in MASLD patients: a randomized controlled trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging globally as a significant problem. The mainstay of treatment is lifestyle intervention (LSI). We hypothesized that providing information regarding LSI and MASLD through a social media application generally used in the respective society would improve clinical outcomes in MASLD more than standard of care (SOC). This is a randomized controlled study in noncirrhotic MASLD patients aged 18–65 years in Thailand. Eligible patients were randomly assigned to either the control (SOC) or intervention arm. Patients in both groups received standard LSI advice. Infographics about MASLD and LSI information were sent to the intervention group every 3–7 days via the LINE official account. The outcomes are changes in liver steatosis and liver stiffness by FIBROSCAN at 24 weeks, as well as weight loss, body composition, and serum alanine aminotransferase (ALT) level between the two groups. A total of 122 patients were enrolled. The median age of eligible participants was 53 years, 64.7% were female, and median body mass index was 27.3 kg/m2. After a complete 24-week study period, both groups had an improvement in weight, ALT level, liver steatosis, and fat mass, but the differences in those changes between groups were not statistically significant. Interestingly, a significant improvement in liver stiffness was observed in the intervention group than in the control group (− 0.7 ± 1.8 kPa vs. 0.1 ± 2.4 kPa, P = 0.035). Encouraging LSI and delivering MASLD information via a social media application (LINE official account) to patients with MASLD demonstrated a better outcome of liver stiffness measurement than SOC.Clinical trial number: TCTR20210304002 (04/03/2021) (http://www.thaiclinicaltrials.org/show/TCTR20210304002).

Evaluation of the Spatial Arrangement of Rabbit Hepatocytes Based on Voronoi Tessellation Following Exposure to Zinc Oxide Nanoparticles.

Zinc oxide nanoparticles have been utilized in different fields over the last decades. These nanoparticles can pose significant risks to various organs such as the liver. This study aimed to evaluate the effects of zinc oxide nanoparticles on liver histology, serum biochemistry, and spatial arrangement of the hepatocytes in the female New Zealand white rabbit. The rabbits received 1, 5, and 10 mg/kg of the zinc oxide nanoparticles (ZnO NPs) intraperitoneally once every 3 days for 28 days. The serum levels of the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and zinc were assessed 48 hr following the first administration. The histopathological changes and Voronoi tessellation were evaluated after the last administration. Our findings showed that the ZnO NPs significantly increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and zinc. The histopathological findings showed ballooning degeneration, and sinusoidal congestion in ZnO NPs administrated groups. The Voronoi tessellation diagrams also confirmed that ZnO NPs changed the regular spatial arrangement of hepatocytes to random and cluster patterns. In conclusion, the ZnO NPs alter the liver spatial arrangement and induce hepatic pathological changes that may affect liver function in rabbits.