Alanine Aminotransferase Levels Research Articles

Outbreak investigation of food poisoning attributed to Omphalotus japonicus using polymerase chain reaction‐based sequencing

AbstractObjectiveThis study aims to report and analyse an outbreak of Omphalotus japonicus poisoning following mushroom ingestion in Taiwan, and to employ PCR methods for accurate identification of the toxic mushrooms involved.MethodsA descriptive observational study was conducted involving a family of four who ingested the mushrooms in the mountainous rural area of Yilan County, Taiwan. Data were collected through interviews with the affected individuals and a review of their medical records. Due to the destruction of the mushroom samples, Polymerase Chain Reaction (PCR) methods were utilized for identification. Genomic DNA was extracted from the raw fruiting bodies, and specific primers targeting the internal transcribed spacer region of the nuclear ribosomal DNA were designed for PCR detection.ResultsThree family members (mother, daughter, and son) experienced gastrointestinal symptoms, including nausea, vomiting, abdominal cramps, and diarrhea, approximately 30 min after consuming the mushrooms. Upon admission to the emergency room, they were hydrated and monitored, with laboratory results showing slightly elevated alanine transaminase levels. The affected individuals recovered within 12 h and were discharged in good condition on day 2. PCR analysis of the mushroom sample confirmed the identification of Omphalotus japonicus, known to produce Illudin S and Illudin M, which cause acute gastrointestinal symptoms. This case represents the first documentation of using PCR‐based sequencing to diagnose Omphalotus japonicus poisoning in the English literature.

Expression of sPD-L1 levels in an ex vivo liver perfusion model.

The programmed cell death protein 1 (PD-1) acts as a central inhibitory immune checkpoint receptor. The soluble form of its primary ligand, sPD-L1, was found to be elevated in serum of patients with cancer, infectious diseases and chronic inflammation. So far, the hepatic origin of sPD-L1 has received relatively little attention and is therefore subject of this study in the context of normothermic machine perfusion (NMP) of liver grafts. sPD-L1 concentrations as well as several well-established clinically relevant laboratory parameters were determined in the perfusate of 16 donor liver grafts undergoing normothermic machine perfusion (NMP) up to 30 hours (h). sPD-L1 levels continuously increased during NMP and significantly correlated with markers of hepatic synthesis (cholinesterase), acute-phase proteins (von Willebrand factor, procalcitonin, antithrombin, interleukin-6, fibrinogen) and liver decay markers (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase). Perfusate leukocytes were in the lower reference range, and decreased after 12h. Mean sPD-L1 levels in the perfusate correlated with donor levels of gamma-glutamyltransferase, alanine aminotransferase, creatinine and blood urea nitrogen. Our study reveals a significant increase of concentration of sPD-L1 following ischemia-reperfusion injury in a hepatic ex vivo model. sPD-L1 concentrations during NMP correlate with established acute-phase proteins and liver cell decay markers suggesting that hepatic sPD-L1 synthesis or shedding increases during the acute phase and cell decay. Furthermore, sPD-L1 correlates with established liver function and synthesis parameters as well as with donor laboratory values and might therefore be a potential biomarker for hepatic function of liver grafts.

Comparative Analysis of the Safety and Feasibility of Laparoscopic Versus Open Segment 7 Hepatectomy.

Laparoscopic hepatectomy has been widely accepted owing to its advantages as a minimally invasive surgery; however, laparoscopic segment 7 (S7) hepatectomy (LSH) has been rarely reported. We aimed to explore the safety and feasibility of LSH by comparing it with open surgical approaches. Twenty-nine patients who underwent S7 hepatectomy between January 2016 and January 2023 were enrolled in this study. The patients' characteristics, intraoperative details, and postoperative outcomes were compared between the 2 groups. No significant differences were observed in the preoperative data. The patients who underwent LSH had significantly shorter hospital stays (P=0.016) but longer operative times (P=0.034) than those who underwent open S7 hepatectomy. No significant differences in blood loss (P=0.614), transfusion (P=0.316), hospital expenses (P=0.391), surgical margin (P=0.442), rate of other complications, postoperative white blood cell count, and alanine aminotransferase and aspartate aminotransferase levels were noted between the 2 groups (P>0.05). For hepatocellular carcinoma, the results showed no differences in either disease-free survival (P=0.432) or overall survival (P=0.923) between the 2 groups. LSH is a safe and feasible surgical procedure that is efficient from an oncological point of view. It may be the preferred technique for lesions in the S7 of the liver.

Integrated metabolomics and network pharmacology to explore the clinical efficacy and mechanism of Yinchenhao decoction combined with nucleoside analogues on chronic hepatitis B

Yinchenhao decoction (YCHD) is widely used in the treatment of damp-heat syndrome of chronic hepatitis B (CHB), but it remains unclear about the active compounds in YCHD and its potential mechanism for treating CHB. The purpose of this work is to evaluate the clinical efficacy of YCHD combined with nucleoside analogues (NAs) for the treatment of CHB. Besides, based on the exact clinical efficacy, we combined serum metabolomics and network pharmacology to screen differential metabolites and related pathways regulated by YCHD to investigate the possible mechanism for treating CHB. It revealed that NAs plus YCHD could significantly improve alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increase HBV-DNA negative rate (P<0.05), reduce the levels of inflammatory factors and LSM (both P<0.05), regulate lipids (P<0.05), and improve the symptoms of traditional Chinese medicine (TCM) (P<0.05) in CHB patients. YCHD was relatively safe. It showed 30 active compounds including chlorogenic acid, geniposide, emodin, quercetin, kaempferol, β-sitosterol and aloe emodin, and 115 key targets which were related to the regulation of lipids and reduction of oxidative stress related to the effect of YCHD in CHB in the network pharmacology analysis. We found 9 core targets and 4 key metabolites according to metabolomics, which were partly consistent with the network pharmacology findings. It proved that network pharmacology combined with metabolomics can well explain the “multi-component-multi-target” mechanism of complex TCM.

Saccharomyces boulardii Mitigates Fructose-Induced Non-Alcoholic Fatty Liver in Rats.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern closely linked to metabolic disorders, including obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that the gut-liver axis plays a critical role in the pathogenesis of NAFLD, with recent research highlighting the influence of gut microbiota, including fungal species such as Saccharomyces boulardii (S. boulardii). This study aimed to evaluate the effects of S. boulardii on lipid metabolism and oxidative stress in a rat model of fructose-induced NAFLD. Materials and Methods: Thirty Wistar rats were divided into three groups: a control group, a fatty liver group induced by 35% fructose supplementation, and a treatment group receiving S. boulardii (100 mg/kg/day) after fructose induction. Results: Biochemical analyses revealed that the treatment group exhibited significantly lower plasma levels of malondialdehyde (MDA), alanine aminotransferase (ALT), total triglycerides, and cholesterol compared to the untreated fatty liver group (p < 0.05). Furthermore, liver tissue analysis showed a marked reduction in lipid accumulation and fatty infiltration in the treatment group, with no visible lipid vacuoles in hepatocytes. The expression of aquaporin-8 (AQP8) and sirtuin-1 (SIRT1), key markers associated with hepatocyte function and lipid metabolism, was significantly higher in the S. boulardii group compared to the fatty liver group (p < 0.001). Conclusions: These findings indicate that S. boulardii supplementation mitigates the metabolic and oxidative stress-related alterations associated with fructose-induced NAFLD. In conclusion, our study suggests that S. boulardii exerts protective effects on the liver by reducing lipid accumulation and oxidative stress, highlighting its potential as a therapeutic intervention for NAFLD.

Impact of zinc oxide nanoparticles on the behavior and stress indicators of African catfish (Clarias gariepinus) exposed to heat stress

This study was designed to assess the role of nano-zinc oxide in mitigating the deleterious effects of heat stress in African catfish (Clarias gariepinus) by evaluating parameters such as aggressive behavior (biting frequency and chasing duration), hematological indicators, and stress-related biochemical markers. A total of 96 catfish were divided into four distinct groups (24 fish/group): The first group (CON) served as the control group, receiving a diet free of nano-zinc oxide. The second group (HS) was exposed to heat stress at 35 °C ± 1 °C. The third group (ZN) was fed a diet containing nano-zinc oxide at 30 mg/kg of the diet, and the fourth group (ZHN) was exposed to heat stress (35 °C ± 1 °C) and fed a diet containing nano-zinc oxide at 30 mg/kg of the diet. The results clarified that the aggressive behavior and cortisol levels were significantly higher (P < 0.05) in the HS group compared to the CON and ZHN groups. Additionally, the level of acetylcholinesterase (AChE) was significantly lower (P < 0.05) in the HS group compared to the CON and ZHN groups. Meanwhile, a significant (P < 0.05) decrease in red blood cells, hemoglobin, packed cell volume, white blood cells, alkaline phosphatase, and lymphocytes, was observed in fish belonging to the HS group, while the levels of alanine aminotransferase, aspartate aminotransferase, neutrophils, and monocytes showed a significant increase (P < 0.05). Supplementation with nano-zinc oxide significantly recovered most hematological and biochemical parameters. In conclusion, nano-zinc oxide contributed significantly to the regulation of the negative impacts of heat stress on fish by reducing aggressive behavior and cortisol levels. Additionally, it improved the levels of AChE and certain hematological and biochemical parameters.

Antiviral Therapy for Chronic Hepatitis B with Mildly Elevated Aminotransferase: A Rollover Study from the TORCH-B Trial.

Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Laboratory profiles of patients hospitalized with COVID-19 pneumonia treated with tofacitinib or placebo: a post hoc analysis from the STOP-COVID trial.

Tofacitinib, an oral Janus kinase inhibitor, has been tested against a placebo in 289 patients with COVID-19 pneumonia. We analyzed the data from the tofacitinib- and placebo-treated patient cohorts to evaluate the laboratory profiles between baseline and day 7. We performed post hoc analyses on the following laboratory tests over time during the first 7 days after randomization: hemoglobin, leukocytes, neutrophils, lymphocytes, platelets, alanine aminotransferase, and aspartate aminotransferase. Through the first 7 days after randomization, the levels of hemoglobin, white blood cells, neutrophils, and platelet counts were not significantly different between patients treated with tofacitinib or a placebo (all p>0.05). Non-significant differences were observed in aspartate aminotransferase levels over time between treatment groups, whereas alanine aminotransferase levels (U/L) were higher among tofacitinib-treated patients compared to placebo-treated patients (mean ratio, 1.30 [95% confidence interval (95%CI) = 1.14-1.48; p<0.01)]. In patients with COVID-19 pneumonia, the use of tofacitinib compared to placebo did not result in clinically meaningful changes in blood counts or liver enzymes over the first 7 days after randomization. NCT04469114.

Elevated Serum Syndecan-1 Levels Are Associated with Obesity-Related Complications in Children

Background: Syndecan-1 plays a crucial role in cell differentiation, growth, adhesion, wound healing, and inflammatory processes. It has been linked to obesity, particularly overweight and chronic low-grade inflammation. Objectives: This study aimed to compare serum syndecan-1 levels between obese children and a healthy control group and to investigate the relationship between serum syndecan-1 levels and renal and cardiovascular complications associated with obesity in children. Methods: We assessed 30 obese and 30 healthy children aged 8 - 16 years. Blood samples were collected from both groups to measure serum aspartate aminotransferase (AST), syndecan-1, fasting blood glucose (FBG), alanine aminotransferase (ALT), creatinine, and urea concentrations. In the obese group, high-density lipoprotein cholesterol (HDL-C), insulin, triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were also measured, along with homeostasis model assessment of insulin resistance (HOMA-IR). Results: The mean serum syndecan-1 levels in the obese and control groups were 15.65 ± 10.01 ng/mL and 6.99 ± 3.79 ng/mL, respectively, with a significantly higher level observed in the obese group (P &lt; 0.005). Significant differences were also found in BMI, BMI SDS, creatinine, AST, and ALT levels between the two groups (P &lt; 0.05), with all parameters being higher in the obese group. A significant positive linear association was identified between syndecan-1 levels and creatinine, TG, and BMI SDS (r = 0.711, r = 0.630, r = 0.682, P &lt; 0.01). Additionally, a strong negative correlation was found between syndecan-1 and HDL-C levels (r = -0.609, P &lt; 0.001). No significant linear relationship was detected between syndecan-1 levels and LDL-C, ALT, AST, glucose, urea, insulin levels, or HOMA-IR measurements (P &gt; 0.05). Linear regression analysis revealed that serum creatinine levels and BMI SDS were significantly linked to changes in syndecan-1 levels. Conclusions: Syndecan-1 is elevated in obese children due to inflammation and may serve as an early biomarker for endothelial damage. It can be useful in detecting obesity-related renal damage and cardiovascular risk in children.

Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer.

Liver cancer is a highly malignant tumor with significant clinical impact. Chemotherapy alone often yields suboptimal outcomes in both the short and long term, characterized by high rates of local recurrence and distant metastasis, leading to a poor long-term prognosis. To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization (DEB-TACE) combined with targeted therapy for the treatment of unresectable liver cancer. We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020. Based on the different treatment regimens administered, patients were divided into the control (36 patients receiving sorafenib alone) and joint (38 patients receiving small particle DEB-TACE combined with sorafenib) groups. We compared liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB)] and serum tumor markers [alpha fetoprotein (AFP)] before and after treatment in both groups. Short-term efficacy measures [complete response (CR), partial response, progression disease, stable disease, objective response rate (ORR), and disease control rate (DCR)] were assessed post-treatment. Long-term follow-up evaluated median overall survival (OS), progression-free survival (PFS), and adverse reaction rates between the two groups. One month post-treatment, the joint group demonstrated significantly higher rates of CR, ORR, and DCR compared to the control group (P < 0.05). Three days after treatment, the joint group showed elevated levels of ALT, AST, and TBIL but reduced levels of ALB and AFP compared to the control group (P < 0.05). The median OS was 18 months for the control group and 25 months for the joint group, while the median PFS was 15 months for the control group and 22 months for the joint group, with significant differences observed (log-rank: χ 2 = 7.824, 6.861, respectively; P = 0.005, 0.009, respectively). The incidence of adverse reactions was not significantly different between the groups (P > 0.05). The combination of small particle DEB-TACE and sorafenib significantly improves both short- and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

Effects of licorice root (Glycyrrhiza glabra) extract on the livers of obese rats.

We have investigated anti-obesity effects of the extract of licorice (Glycyrrhiza glabra) root in rats with diet-induced obesity and hyperlipidemia by using histopathological and biochemical methods. Thirty-two Wistar albino rats were divided to four groups of eight: normal control (C), high fat diet (HFD), high fat Diet + Glycyrrhiza glabra (HFD+M), and normal diet with Glycyrrhiza glabra (M). The high fat diet contained 300 g/kg fat (4000 kcal/kg); the daily dosage of Glycyrrhiza glabra extract was 1g/kg body weight by orogastric gavage. Supplementation of Glycyrrhiza glabra extract dramatically reduced increases in body weight caused by the induction of obesity. A hepatoprotective effect of Glycyrrhiza glabra extract was supported by the almost normal histology in the livers of the HFD+M rats, in contrast to the degenerative changes in the HFD rats, which included macrovesicular and microvesicular fat deposits, hydropic degeneration, dilatation of sinusoids and coagulation necrosis of some hepatocytes. Serum levels of alanine transaminase (ALT), aspartic transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol (HDL and LDL) and triglycerides, were ameliorated by Glycyrrhiza glabra extract treatment. We conclude that Glycyrrhiza glabra extract given together with HFD could prevent obesity and reduce liver damage in rats.

Mixed active metabolites of the SNP-6 series of novel compounds mitigate metabolic dysfunction-associated steatohepatitis and fibrosis: promising results from pre-clinical and clinical trials

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern with no effective pharmacological treatments. SNP-630, a newly developed synthetic molecule with multiple mechanisms of action, and a mixture of two of its active metabolites (SNP-630-MS) inhibit CYP2E1 expression to prevent reactive oxygen species generation, thereby reducing the accumulation of hepatic triglycerides and lowering chemokine levels. This study investigated the SNP-630’s potential to alleviate the liver injury in MASH and its efficacy in both a mouse model and patients with MASH to identify a drug candidate that targets multiple pathways implicated in MASH.MethodsSNP-630 and SNP-630-MS were separately administered to the MASH mouse model. The tolerability, safety, and efficacy of SNP-630-MS were also evaluated in 35 patients with MASH. The primary endpoint of the study was assessment of the changes in serum alanine aminotransferase (ALT) levels from baseline to week 12, while the secondary endpoints included the evaluation of liver inflammation, steatosis, and fibrosis parameters and markers.ResultsSNP-630 treatment in mice improved inflammation, liver steatosis, and fibrosis compared with that in the MASH control group. Both SNP-630 and SNP-630-MS treatments markedly reduced ALT levels, hepatic triglyceride content, and the expression of inflammatory cytokines monocyte chemoattractant protein 1 and fibrotic collagen (i.e., Col1a1, Col3a1, and Timp1) in mice. In the clinical trial, patients treated with SNP-630-MS exhibited significant improvement in ALT levels at week 12 compared with baseline levels, with no reports of severe adverse events. This improvement in ALT levels surpassed that achieved with most other MASH candidates. SNP-630-MS demonstrated potential antifibrotic effects, as evidenced by a significant decrease in the levels of fibrogenesis-related biomarkers such as CCL4, CCL5, and caspase 3. Subgroup analysis using FibroScan measurements further indicated the efficacy of SNP-630-MS in ameliorating liver fibrosis.ConclusionsSNP-630 and SNP-630-MS demonstrated favorable results in mice. SNP-630-MS showed excellent tolerability in mice and patients with MASH. Efficacy analyses indicated that SNP-630-MS improved liver steatosis and injury in patients with MASH, suggesting that SNP-630 and 630-MS are promising therapeutic options for MASH. Larger scale clinical trials remain warranted to assess the efficacy and safety of SNP-630 in MASH.Trial registration: ClinicalTrials.gov NCT03868566. Registered 06 March 2019-Retrospectively registered, https://clinicaltrials.gov/study/NCT03868566

Comparison of Two-Dimensional Shear Wave Elastography Between Two Different Instruments for Hepatocellular Carcinoma Patients.

This study aimed to investigate and compare 2-dimensional shear wave elastography (2D-SWE) measurements and influencing factors among 2 different devices and to evaluate the ability and influencing factors of these measurements to assess liver fibrosis. From October 2022 to September 2023, 290 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers were prospectively included. The 2D-SWE measurements were performed using AixPlorer V (SEmean) and APLIO i900 (CEmean). This study compared 2D-SWE measurements between instruments for evaluating the liver fibrosis stage and analyzed the potential influencing factors. The 2D-SWE measurements obtained by the 2 instruments were significantly different (P < .001), but the differences were significant only for patients with stage F4 liver fibrosis (P < .001) and not for volunteers or patients with stage F0-F3 liver fibrosis (all P > .050). Multivariate linear regression analysis revealed that the factors independently influencing the SEmean were alanine aminotransferase (ALT) (P = .034) and liver fibrosis stage (P < .001), while fibrosis stage (P = .028) was the only factor influencing the CEmean. Although 2D-SWE from the 2 different instruments was capable of detecting liver fibrosis, it yielded varying results in HCC patients. These discrepancies were predominantly observed in patients with F4 liver fibrosis but not in healthy adults or patients with F0-F3 liver fibrosis. One potential contributing factor to the differences between instruments could be ALT levels.

The Impact of Labor Oxytocin Use on Newborn Liver Enzymes.

Oxytocin is commonly used during labor and delivery for induction of labor and prevention of postpartum hemorrhage. While previous studies have explored the effects of labor oxytocin use on maternal and neonatal outcomes, there is a paucity of research on its impact on newborn liver enzyme function. This study aimed to assess the effects of labor oxytocin use on liver enzyme function in newborns. A case-control study was conducted. The case group consisted of 70 newborns whose mothers received oxytocin during labor, while the control group consisted of 70 newborns whose mothers did not receive oxytocin. Complete blood count (CBC), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total and indirect bilirubin levels were measured in all newborns on the second day of life. The levels of AST and total and indirect bilirubin were found to be higher in the case group than in the control group (51 vs. 42, 7.8 vs. 4.6, and 7.4 vs. 4, respectively; p < 0.005). The levels of CPK and LDH were also higher in the case group (p < 0.005). However, the difference in ALT levels was not significant between the study groups. The observed increase in liver enzymes in this study can indicate the effect of maternal oxytocin on the newborn's liver function. While the changes in liver enzyme levels due to oxytocin use were not found to be high enough to cause liver damage, the increase in CPK and LDH levels could potentially elevate bilirubin levels due to hemolysis. Further research is needed to confirm these findings and explore the underlying mechanisms.

Multi-Protective Effects of Petunidin-3-O-(trans-p-coumaroylrutinoside)-5-O-glucoside on D-Gal-Induced Aging Mice

Petunidin-3-O-(trans-p-coumaroylrutinoside)-5-O-glucoside (PtCG), the primary anthocyanin ingredient in Lycium ruthenicum Murr., possesses a range of biological activities, including antioxidative properties and melanin inhibition. This study aimed to investigate the protective effect of PtCG on D-galactose (D-gal)-induced aging in female mice and elucidate the underlying molecular pathways. Behavioral experiments, including the MWW and Y-maze tests, revealed that PtCG significantly ameliorated cognitive decline and enhanced learning and memory abilities in aging mice. Regarding biochemical indicators, PtCG considerably improved superoxide dismutase (SOD) and glutathione (GSH) activity while reducing malondialdehyde (MDA) and acetylcholinesterase (AChE) levels in the hippocampus and serum. Furthermore, PtCG ingestion alleviated liver injury by decreasing alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (AKP) levels, and attenuated renal damage by reducing blood urea nitrogen (BUN) and uric acid (UA) levels. Transmission electron microscopy (TEM) results demonstrated that PtCG restored the function and quantity of synapses in the hippocampus. Hematoxylin and eosin (H&amp;E), Masson’s trichrome, and Nissl staining revealed that PtCG significantly improved the relevant pathological characteristics of liver and hippocampal tissues in aging mice. The molecular mechanism investigation showed that PtCG downregulated the protein expression of microglial marker ionized calcium-binding adapter molecule 1 (Iba1), astrocytic marker glial fibrillary acidic protein (GFAP), β-secretase 1 (BACE-1), and amyloid-beta1–42 (Aβ1–42) in the hippocampus of aging mice. The protein expression of inflammatory pathway components, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β), was also suppressed. These findings suggest that PtCG may possess anti-aging properties, with its mechanism of action potentially linked to the attenuation of neuroinflammation, oxidative stress, and liver and kidney damage. PtCG may have future applications as a functional food for the treatment of aging-related disorders.

Alterations of Nutrient Elements in Hepatocellular Carcinoma Patients Treated with Atezolizumab-Bevacizumab

Currently, the combination of atezolizumab and bevacizumab (Atez/Bev) is recommended as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC). However, there is a lack of research on the levels of nutrient elements in advanced HCC patients receiving Atez/Bev treatment. In this study, data from 35 patients with advanced HCC and 37 healthy individuals of similar age and sex were included. The levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in patients with HCC. These levels returned to the reference range after three rounds of Atez/Bev treatment. Additionally, the levels of blood urea nitrogen and creatinine (Cr) increased after Atez/Bev treatment. In HCC patients, the levels of calcium (Ca), iron (Fe), and copper (Cu) were significantly higher, while the levels of sodium (Na), magnesium (Mg), and zinc (Zn) were significantly lower compared to healthy individuals. These changes were reversed after Atez/Bev treatment. In conclusion, our findings indicate that treatment with Atez/Bev influences the levels of Ca, Fe, Cu, Na, Mg, and Zn in patients with HCC. The alterations in these elements caused by Atez/Bev treatment require mechanistic research in the future.

Prognostic value of elevated transaminase levels as predictors of adverse outcomes in patients with acute myocardial infarction

Aim. To assess the prevalence of elevated serum liver transaminases (LTs), including alanine aminotransferase (ALT) and aspartate aminotransferase (ALT), and their impact on in-hospital and long-term mortality in patients with acute myocardial infarction (AMI).Materials and methods. The prospective observational study included 416 consecutive AMI patients (median age 65 years, 40.9% female, 46.9% with ST elevation) without prior liver diseases, who underwent coronary angiography within 24 hours after hospitalization. AST and ALT levels were measured upon admission. LTs were considered as abnormal when their levels exceeded the local upper limit of normal. Clinical endpoints were all-cause in-hospital and 18-month mortality. Associations between clinical endpoints and various risk factors, including LT levels, were assessed by the multivariate logistic regression analysis.Results. Elevated LT levels were seen in 28.6% of AMI patients: an isolated increase in ALT was noted in 17.8% of patients, while an isolated increase in AST was registered in 25% of cases. In-hospital and 18-month mortality was 5.8 and 11.3%, respectively. Abnormal LT levels were associated with the presence of ST elevation (odds ratio (OR) 1.873, 95% confidence interval (CI) 1.218–2.881, p = 0.004), lower systolic and diastolic blood pressure (OR 0.993, 95% CI 0.986–1.0, p = 0.04 and 0.979, 95% CI 0.964–0.994, p = 0.007, respectively), higher Killip class (OR 1.510, 95% CI 1.142–1.999, p = 0.004), and higher creatinine level (OR 1.010, 95% CI 1.003–1.016, p = 0.004). In the multivariate analysis, elevated LT levels were independently associated with in-hospital and 18-month mortality (OR 3.607, 95% CI 1.199–10.848, p = 0.022 and 2.182, 95% CI 1.011–4.708, p = 0.047, respectively).Conclusion. Elevated LT levels were present in about a third of patients with AMI. They were associated with specific clinical, biological, and prognostic features, including in-hospital and long-term mortality in AMI patients.

Atractylodes Lancea and Its Constituent, Atractylodin, Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease via AMPK Activation.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which encompasses a spectrum of conditions ranging from simple steatosis to hepatocellular carcinoma, is a growing global health concern associated with insulin resistance. Since there are limited treatment options for MASLD, this study investigated the therapeutic potential of Atractylodes lancea, a traditional herbal remedy for digestive disorders in East Asia, and its principal component, atractylodin, in treating MASLD. Following 8 weeks of high-fat diet (HFD) feeding, mice received oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea. In HFD-fed mice, Atractylodes lancea treatment reduced the body weight; serum triglyceride, total cholesterol, and alanine aminotransferase levels; and hepatic lipid content. Furthermore, Atractylodes lancea significantly ameliorated fasting serum glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance levels in response to HFD. Additionally, a glucose tolerance test demonstrated improved glucose homeostasis. Treatment with 5 or 10 mg/kg atractylodin also resulted in anti-obesity, anti-steatosis, and glucose-lowering effects. Atractylodin treatment resulted in the downregulation of key lipogenic genes (Srebf1, Fasn, Scd2, and Dgat2) and the upregulation of genes regulated by peroxisome proliferator-activated receptor-α. Notably, the molecular docking model suggested a robust binding affinity between atractylodin and AMP-activated protein kinase (AMPK). Atractylodin activated AMPK, which contributed to SREBP1c regulation. In conclusion, our results revealed that Atractylodes lancea and atractylodin activated the AMPK signaling pathway, leading to improvements in HFD-induced obesity, fatty liver, and glucose intolerance. This study suggests that the phytochemical, atractylodin, can be a treatment option for MASLD.

Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B

Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of “piecemeal necrosis”. In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.

Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia-Reperfusion Rat Model via Endoplasmic Reticulum Stress.

Acute mesenteric ischemia can lead to severe liver damage due to ischemia-reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ.