Serum Alanine Aminotransferase Levels Research Articles

Effect of chronic alcohol consumption on oral microbiota in rats with periodontitis.

The imbalance of oral microbiota can contribute to various oral disorders and potentially impact general health. Chronic alcohol consumption beyond a certain threshold has been implicated in influencing both the onset and progression of periodontitis. However, the mechanism by which chronic alcohol consumption affects periodontitis and its association with changes in the oral microbial community remains unclear. This study used 16S rRNA gene amplicon sequencing to examine the dynamic changes in the oral microbial community of rats with periodontitis influenced by chronic alcohol consumption. Twenty-four male Wistar rats were randomly allocated to either a periodontitis (P) or periodontitis + alcohol (PA) group. The PA group had unrestricted access to alcohol for 10 weeks, while the P group had access to water only. Four weeks later, both groups developed periodontitis. After 10 weeks, serum levels of alanine aminotransferase and aspartate aminotransferase in the rats' serum were measured. The oral swabs were obtained from rats, and 16S rRNA gene sequencing was conducted. Alveolar bone status was assessed using hematoxylin and eosin staining and micro-computed tomography. Rats in the PA group exhibited more severe periodontal tissue damage compared to those in the periodontitis group. Although oral microbial diversity remained stable, the relative abundance of certain microbial communities differed significantly between the two groups. Actinobacteriota and Desulfobacterota were more prevalent at the phylum level in the PA group. At the genus level, Cutibacterium, Tissierella, Romboutsia, Actinomyces, Lawsonella, Anaerococcus, and Clostridium_sensu_stricto_1 were significantly more abundant in the PA group, while Haemophilus was significantly less abundant. Additionally, functional prediction using Tax4Fun revealed a significant enrichment of carbohydrate metabolism in the PA group. Chronic alcohol consumption exacerbated periodontitis in rats and influenced the composition and functional characteristics of their oral microbiota, as indicated by 16S rRNA gene sequencing results. These microbial alterations may contribute to the exacerbation of periodontitis in rats due to chronic alcohol consumption.

Delayed treatment with hydro-ethanolic extract of Khaya grandifoliola protects mice from acetaminophen-hepatotoxicity through inhibition of c-Jun N-terminal kinase phosphorylation and mitochondrial dysfunction

The use of N-acetylcysteine against acetaminophen(APAP)-induced hepatotoxicity, a leading cause of liver injury, has several drawbacks, including short therapeutic windows. Khaya grandifoliola (Meliaceae) has been traditionally used to manage liver-related diseases, and many reports have confirmed its hepatoprotective properties. However, its therapeutic potential as an antidote against APAP-induced hepatotoxicity has yet to be proven in a clinically relevant model. This study aimed to verify the efficacy of delayed treatment with the hydroethanolic extract of K. grandifoliola (KgE) in suppressing the early injury phase of APAP pathophysiology. KgE was analyzed using HPLC/UV. Acute oral toxicity tests were conducted in mice to determine the therapeutic dose of KgE. Mice were treated with 300 ​mg/kg APAP; 1h and 12h later, they were treated with either predetermined doses of KgE or 20 ​mg/kg c-Jun N-Terminal Kinase (JNK) inhibitor SP600125, which served as a reference antidote. At 6h and 24h after APAP treatment, the parameters of liver damage and mitochondrial dysfunction, phosphorylation of JNK, and mitochondrial translocation were assessed. KgE at a dose of 5000 ​mg/kg was safe for mice. Accordingly, 100, 200, and 400 ​mg/kg were selected as curative treatments. Delayed administration of KgE reversed the histopathological changes in the liver, inhibited serum levels of alanine aminotransferase, reduced the liver content of nitric oxide and malondialdehyde, and restored hepatic glutathione pools and superoxide dismutase and catalase activities in APAP-intoxicated mice. Moreover, KgE prevented APAP-induced JNK phosphorylation and p-JNK mitochondrial translocation and rescued the activities of mitochondrial enzyme complexes II and V. HPLC/UV analysis revealed the presence of gallic acid, Quercetin and Silibinin, with retention times of 3.77, 11.63 and 11.95 ​min as the major active ingredients present in KgE. Our findings demonstrate that post-treatment with KgE protects the mouse liver from APAP-hepatotoxicity through the inhibition of JNK activation and mitochondrial dysfunction.

Evaluation of Cytotoxicity and Acute Oral Toxicity of Saline Extract and Protein-Rich Fraction from Moringa oleifera Lam. Leaves.

Moringa oleifera Lam. (horseradish tree) leaves demonstrate high nutritional value, are rich in proteins, and are widely used in folk medicine and food. This study investigated the presence of secondary metabolites and antinutritional proteins in leaf extract (LE) and the protein-rich fraction (PRF) derived from M. oleifera leaves, as well as the cytotoxicity to human cells, hemolytic activity, and in vivo acute toxicity and genotoxicity in mice. The flavonoids rutin and vitexin as well as trypsin inhibitors and lectins were detected in LE and PRF. Neither sample demonstrated toxicity against human peripheral blood mononuclear cells and both showed low hemolytic action. In vivo, LE and PRF did not show antinutritional effects and caused no death. The hematological parameters of the animals in the treated group were similar to those of the control. A significant increase in the serum levels of alanine aminotransferase and a discrete leukocyte infiltration with cytoplasmic vacuolization of the hepatocytes in the liver were detected in LE-treated animals. The preparations were not genotoxic or mutagenic. This study shows that LE and PRF are not antinutritional agents and presented low acute toxicity and no genotoxicity or mutagenicity. The present study contributes to the determination of the safety of using M. oleifera leaf proteins.

Effect of crowding stress on liver health, gut permeability and gut microbiota of genetically improved farmed tilapia (GIFT, Oreochromis niloticus)

This study investigated the effects of crowding stress on liver and gut health in genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Fish averaging 18.90 ± 0.01 g were reared at low (LD, 5 g/L) or high densities (HD, 100 g/L) for 14 days. The analysis revealed that the HD group significantly increased serum cortisol, glucose and adrenocorticotropic hormone (ACTH) levels in GIFT (P < 0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated in the HD group (P < 0.05). TUNEL staining of liver tissues revealed that the fluorescence intensity indicating apoptosis was significantly higher in the HD group (P < 0.05). Additionally, the HD group exhibited increased expression of p53 and Caspase3 in the liver (P < 0.05). In comparison to the LD group, the HD group showed a significant increase in gut superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content (P < 0.05). The expressions of inflammatory-related genes (tnfα, il-1β, il-8, and il-6) and pro-apoptotic genes (p53 and Caspase7) were significantly upregulated in the gut of the HD group (P < 0.05). Serum contents of D-lactate and diamine oxidase (DAO) were significantly elevated in HD group as comparison to LD group (P < 0.05), and significantly higher serum FITC-CM-dextran was observed in HD group versus LD group following oral gavage (P < 0.05). Furthermore, the HD group down-regulated the expressions of gut tight junction proteins (tjp2a, hif-1a, and zo-1) (P < 0.05), and significantly up-regulated the protein expression of phosphorylated myosin light chain 2 (P-MLC2) (P < 0.05). The 16S rDNA gene sequencing results indicated that the relative abundance of Cetobacterium was significantly lower (P < 0.05), and Enterovibrio and Weissella were significantly higher in the HD group (P < 0.05). Overall, crowding stress negatively affects GIFT liver and gut health, which is caused by inducing hepatic and intestinal apoptosis, impairing intestinal barrier function, and disrupting the gut microbiota.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory, anti-fibrotic, and antioxidant properties in rats

Objective: To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity. Methods: Different doses of Levisticum officinale extract were given orally to rats for 10 days, then rats received a single dose of CCl4 (2.5 mL/kg, 50% v/v in liquid paraffin). Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture. Moreover, antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured. Results: Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure, improved serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, total bilirubin, and total protein, enhanced glutathione content and superoxide dismutase and catalase activities in the liver, as well as decreased plasma and hepatic malondialdehyde levels. Immunohistochemical results demonstrated that the extract reduced Ki-67 and α-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract. Moreover, Levisticum officinale extract markedly decreased the gene expressions of TNF-α, 1L-6, TGF-β1, MCP-1, and COX-2. Conclusions: Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant, anti-inflammatory, and anti-fibrotic activities.

Explore the action mechanism of Danggui Buxue decoction on chronic heart failure in rats by proteomics and untargeted metabolomics

Background and aimDanggui Buxue Decoction (DBD) has been applied to alleviate chronic heart failure (CHF) in clinics, however, its mechanism is still unclear. This study investigates the potential action mechanism of DBD for rats with CHF combined with liver injury. Experimental procedureFor this purpose, this study established a CHF rat model. The change of proteins in myocardial tissues was identified by proteomics and then further verified using western blotting. Additionally, metabolomics revealed the metabolic pathways associated with liver injury in CHF rats. Results and conclusionAnimal studies demonstrated that DBD could relieve CHF as it significantly reduced serum levels of brain natriuretic peptide (BNP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in CHF rats, and promoted the activity of catalase (CAT), glutathione peroxidase (GSH-Px), cytochrome oxidase (COX), and succinate dehydrogenase (SDH) in myocardial tissues. Myocardial proteomics analysis revealed that DBD improved myocardial mitochondria and peroxisomes function by regulating the expression of proteins associated with energy metabolism and oxidative damage. Western blotting confirmed that DBD upregulated the expression of proteins in the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog-1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α)/peroxisome proliferator-activated receptor beta (PPAR β) signaling pathway, which also proved the efficacy of DBD in alleviating CHF in rats. Hepatic metabolomics analysis showed that DBD could restore the damaged liver function of CHF rats via metabolic pathways, including the metabolism of lipid, vitamin, and amino acids. In conclusion, this study unveiled a novel action mechanism of DBD in the treating ISO-induced CHF and liver injury based on proteomics and metabolomics. These results lay a scientific basis for the widespread application of DBD in the cardiovascular field.

Effects of Akkermansia muciniphila on Gut Morphology, Antioxidant Indices, and Gut Microbiome of Mice Under Heat Stress.

Nutritional manipulations can reduce the detrimental effects of heat stress on animal health and production. Akkermansia muciniphila (AM) is an innovative beneficial bacteria and can be used for conventional use as dietary supplements and pharmaceutical application. This study aimed to investigate the effects of administering AM on gut morphology, antioxidant indices, and gut microbiome of mice during heat stress. A total of 24 BALB/c mice were randomly assigned to three groups including the control group (CON), heat stress group (HS), and AM administration under heat stress group (AM). Our results showed heat stress significantly increased the water consumption of mice. Administration of AM did not improve feed intake or weight gain. The serum levels of alanine aminotransferase and aspartate aminotransferase as well as antioxidant parameters were not different among the three groups. Heat stress decreased the jejunal villus height, and AM could reverse this effect. AM administration significantly increased the relative abundance of Verrucomicrobiota at the phylum level. At the genus level, heat stress and AM groups tended to have a lower abundance of Alloprevotella. In addition, AM tended to increase the relative abundance of [Eubacterium]_xylanophilum_group in comparison with the other two groups. In summary, administration of AM can alleviate the damage of heat stress to the jejunum. However, it has no effect on serum antioxidant parameters, and its effect on the cecal microbiota is limited.

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.

Introduction: Cigarette smoke (CS) exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) at 0, 150, 300, or 600μg/L for 2h a day, 5days a week for 2weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Discussion: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.

Effects of Sesamin in Animal Models of Obesity-Associated Diseases: A Systematic Review and Meta-Analysis.

As living standards have improved and lifestyles have undergone changes, metabolic diseases associated with obesity have become increasingly prevalent. It is well established that sesamin (Ses) (PubChem CID: 72307), the primary lignans in sesame seeds and sesame oil, possess antioxidant and anti-inflammatory effects. In this study, a systematic review and meta-analysis of the effects of Ses on animal models of obesity-related diseases was performed to assess their impact on relevant disease parameters. Importantly, this study sought to provide insights for the design of future human clinical studies utilizing Ses as a nutritional supplement or drug. This study conducted a comprehensive search in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library, identifying English language articles published from inception to April 2023. The search incorporated keywords such as "sesamin," "obesity," "non-alcoholic fatty liver disease," "type 2 diabetes mellitus," and "metabolic syndrome." The meta-analysis included 17 articles on non-alcoholic fatty liver disease, type 2 diabetes, and metabolic syndrome. Overall, the pooled results demonstrated that Ses significantly reduced levels of total serum cholesterol (P = .010), total serum triglycerides (P = .003), alanine transaminase (P = .003), and blood glucose (P < .001), and increased high-density lipoprotein cholesterol levels (P = .012) in animal models of nonalcoholic fatty liver disease. In the type 2 diabetes model, Ses mitigated drug-induced weight loss (P < .001), high-fat-diet-induced weight gain (P < .001), and blood glucose levels (P = .001). In the metabolic syndrome model, Ses was associated with a significant reduction in body weight (P < .001), total serum cholesterol (P < .001), total serum triglycerides (P < .001), blood glucose (P < .001), and alanine transaminase levels (P = .039). The meta-analysis results of this study suggest that Ses supplementation yields favorable effects in animal models of obesity-related diseases, including hypolipidemic, insulin-lowering, and hypoglycemic abilities, as well as organ protection from oxidative stress and reduced inflammation. PROSPERO registration No. CRD42023438502.

Investigating hemolysis, elevated liver enzymes and low platelet count in preeclampsia: A case-control study in Ghana.

Preeclampsia poses a heightened risk for women, particularly in the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, leading to adverse outcomes for both mothers and newborns. The incidence of HELLP syndrome tends to be notably higher among women with preeclampsia compared with those with normotensive pregnancies. However, there is a dearth of research on the frequency of HELLP syndrome within the context of preeclampsia specifically in Ghana. Furthermore, the potential predictive value of serum erythrocyte adenylate kinase (EAK), a marker of hemolysis, in anticipating the onset of preeclampsia remains largely unexplored. Conducted between May 2020 and April 2022, this research employed a case-control methodology at the War Memorial and Upper East Regional Hospitals. A total of 291 pregnant women participated, comprising 111 diagnosed with preeclampsia and 180 control subjects, aged between 18 and 43 years. Venous blood samples were collected and subjected to analysis for platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and EAK, utilizing automated analyzers, alongside the ELISA technique. Diagnosis of HELLP syndrome was established using the Mississippi triple-class definition. The median serum ALT level (with interquartile range) was significantly elevated in the preeclampsia group compared with controls [20.0 (13.7-27.0) vs. 13.0 (9.4-18.6); p < 0.001]. Moreover, the frequency of Mississippi class 3 HELLP syndrome was notably higher among preeclampsia cases (2/111; 1.8%) compared with controls (1/180; 0.6%). Serum ALT emerged as the superior predictor of preeclampsia, outperforming LDH (with an area under the curve of 0.73 compared with 0.58). The sensitivity and specificity of ALT were measured at 47.8% and 87.2%, respectively. Although the occurrence of HELLP syndrome in preeclampsia cases appears relatively low, it may escalate as the prevalence of preeclampsia is anticipated to rise in low and middle-income nations.

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

Radioactive iodine-125 (125I) microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors, especially hepatocellular carcinoma. Patients with hepatocellular carcinoma frequently experience portal vein embolism, which exacerbates the difficulty and complexity of treatment. 125I particles, used in local radiotherapy, can directly act on tumor tissue and reduce damage to surrounding healthy tissue. Through retrospective analysis, this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment. To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function. The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed. Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein (combination group), while 44 patients received treatment with transcatheter arterial chemoembolization alone (control group). The therapeutic effects on tumor lesions, primary liver cancer, and portal vein tumor embolisms were compared between the two groups. Changes in relevant laboratory indexes before and after treatment were evaluated. The t test was used to compare the measurement data between the two groups, and the χ 2 test was used to compare the counting data between groups. The tumor lesion response rate in the combination group (59.62% vs 38.64%) and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus (80.77% vs 59.09%) were significantly greater than those in the control group (χ 2 = 4.196, 5.421; P = 0.041, 0.020). At 8 wk after surgery, the serum alpha-fetoprotein, portal vein main diameter, and platelet of the combined group were significantly lower than those of the control group, and the serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly greater than those of the control group (t = 3.891, 3.291, 2.330, 3.729, 3.582, 4.126; P < 0.05). The serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery (P < 0.05), and the peripheral blood platelet, alpha-fetoprotein, and main portal vein diameter were significantly less than those of the same group before surgery (P < 0.05). In patients with primary liver cancer and a thrombus in the portal vein, transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone. However, during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH

Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10–20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients’ serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis.

Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study.

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.

Comparative Evaluation of Diabetes Complication Using Liver Function Parameters as Indices between Male and Female Alloxan Induced Diabetic Rats

It is known that diabetes causes liver damage. On the other hand, because most cases of liver damage have been investigated in males, examining the relationship of this disease in both sexes is of great importance. This study was aimed at, comparatively evaluating diabetic complications using histopathological examination and liver function parameters as indices in alloxan-induced diabetic rats. A total of 24 male and female rats divided into four groups of six animals each were used for the experiment. Group A were female control, Group B were male control while group C and D were alloxan induced diabetic female and male rats respectively. Groups A and B were non diabetic rats fed with rat diet all through the experiment. Group C and D were diabetes induced with a single intraperitoneal injection of alloxan (120mg/kg). At the end of the inducement period, the rats were fasted overnight and sacrificed. Blood was collected by ocular puncture for the determination of fasting plasma glucose (FPG) and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB), total protein (TP) and albumin (ALB) using spectrophotometric method. Histology of the liver was determined by H and E technique. The results showed the experimental group C (365.83±43.6mg/dl) and D (368.94±43.93mg/dl) had significantly elevated levels of FPG when compared with the controls group A (116.00±9.11mg/dl) and B (108.33±5.5mg/dl) confirming the induction of diabetes (P=0.000). The liver of both male and female diabetic rats showed ballooning degeneration. In the males, these were arranged in normal sheets and cord around central vein in some areas of the center, on the other hand, the central vein of the female diabetic rats appears slightly enlarged containing blood clots and the arrangement of the hepatocytes in sheets or cords around the central vein was completely distorted. There was no significant difference (p&gt;0.05) in the mean serum levels of ALP, AST, ALT, DB, TP and ALB in female diabetics when compared to male diabetic rats. The mean serum level of TB was significantly reduced (p=0.004) in female diabetics (0.53±0.05) than in the male diabetic albino rats (0.69±0.09). This study showed the liver histology and function are variably altered in diabetes mellitus. Further research on the causes of liver damage will help us to unravel the pathogenesis of diabetes and its complications.

Ticlopidine protects hepatic ischemia-reperfusion injury via suppressing ferroptosis

Hepatic ischemia-reperfusion injury (IRI) is a major cause of liver damage during hepatic resection, transplantation, and other surgical procedures, often leading to graft failure and liver dysfunction. Recent studies have identified ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, as a key contributor to IRI. In this study, we investigated the protective effects of Ticlopidine, a thienopyridine compound and platelet aggregation inhibitor, on hepatic IRI. Using a C57BL/6J mouse model, we demonstrated that prophylactic Ticlopidine treatment significantly reduced necrotic and fibrotic areas in liver tissues, as well as serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Prussian Blue staining revealed that Ticlopidine pretreatment decreased iron accumulation in hepatic tissues, whereas markers of lipid peroxidation (malondialdehyde and 4-hydroxynonenal) and ferroptosis (PTGS2) were significantly downregulated. Additionally, Ticlopidine ameliorated inflammatory infiltration as indicated by reduced Gr-1 staining. In vitro, Ticlopidine dose-dependently inhibited ferroptosis induced by various inducers in liver cancer cell lines HUH7 and fibrosarcoma cells HT1080. The protective effects involved partial rescue of lipid peroxidation, significant reduction of ferrous iron levels, and strong protection against mitochondrial damage. These findings suggested that Ticlopidine acts as a broad-spectrum ferroptosis inhibitor, offering a promising therapeutic approach for protecting the liver against IRI.

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

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

Assessment of Liver Involvement in Patients With Type 2 Diabetes Mellitus in Basrah City, Iraq, Using FibroScan and Correlation With Risk Factors.

Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases caused by the accumulation of fat in the liver, which can progress to fibrosis, cirrhosis, and primary liver cancer. Insulin resistance is a causative factor in the development of NAFLD. FibroScan, or transient elastography, is a noninvasive imaging technique for evaluating liver disease. Aim To use FibroScan for evaluating liver involvement in type 2 diabetes mellitus (T2DM) patients with some associated risk factors. Materials and methods A cross-sectional prospective study was conducted from February to August 2023 in the outpatient clinic of Basrah Gastroenterology and Hepatology Hospital. Data collection included demographic data, past medical history, and biochemical tests including fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid profile (consisting of low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum triglycerides, and total cholesterol), then, patients underwent FibroScan examination. Results The study included 50 patients with T2DM, of whom 23 (46%) were male and 27 (54%) were female. The mean age of the studied population was 47.72 ± 8.31 years, with a range of 28-64 years. The mean BMI was 28.44 ± 4.24, with most patients being either overweight or obese. The fibrosis score was 4.74 ± 1.02 kPa (stage 0), while the mean steatosis score was 282.88 ± 44.99 (grade III). Diastolic blood pressure (BP), serum ALT, and serum HDL level were the variables that showed statistically significant differences when compared according to the stages of steatosis measured by FibroScan, with p-values of 0.016, 0.048, and 0.028, respectively. Conclusion Some risk factors associated with diabetes, such as dyslipidemia, liver enzymes, and BP, are highly associated with the development of steatosis rather than fibrosis.

Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator-activated receptor gamma in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases worldwide, characterized by the presence of lipid droplets. Rab18 is an important lipid droplet protein; however, its effects and mechanisms of action on NAFLD remain unclear. Free fatty acid-stimulated AML-12 cells and high-fat diet (HFD)-fed mice were used as NAFLD models. Lentiviruses overexpressing Rab18 (Rab18-OE) or knockdown (Rab18-KD) were used to generate stable cell lines for genetic analysis. Blood serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and leptin were measured using a biochemical autoanalyzer. Hematoxylin and eosin staining was performed to detect pathological damage to the liver. Lipid accumulation in the cells was assessed by Oil Red O staining. Target expression was measured using qPCR, western blotting, and immunocytochemistry. Rab18 mRNA and protein expression levels increased in free fatty acid-stimulated AML-12 cells and the livers of HFD-fed mice. Rab18-OE increased lipid accumulation in vitro, which was attenuated by Rab18-KD. In vivo, Rab18-OE augmented liver pathological damage, serum alanine aminotransferase/aspartate aminotransferase activity, and triglyceride, total cholesterol, and low-density lipoprotein levels, whereas Rab18-KD decreased these indicators. Rab18-KD also downregulated blood glucose levels in HFD-fed mice. Mechanistically, Rab18-OE and Rab18-KD regulated the mRNA and protein expression levels of perilipin 2 (PLIN2) and peroxisome proliferator-activated receptor gamma (PPARγ) in vitro and in vivo, respectively. Immunocytochemistry revealed that Rab18 colocalized with PLIN2 and PPARγ in AML-12 cells. Rab18 expression was elevated in vitro and in vivo in the NAFLD mouse model. Rab18 regulates PLIN2 and PPARγ expression to exaggerate liver injury and lipid accumulation in patients with NAFLD. Thus, Rab18 may be a crucial protein in this disease and a potential therapeutic target.

Active surveillance of hepatitis E: a 10-year epidemiological analysis in a city in eastern China

ABSTRACT Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50–69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.

Potential role of two-dimensional shear wave elastography, including liver stiffness measurement and dispersion slope, for management of chronic hepatitis B.

This study assessed the use of liver stiffness (LS) and dispersion slope (DS) in classifying patients with chronic hepatitis B (CHB) by the necessity of antiviral treatment. A retrospective review examined 249 patients with CHB (male:female, 107:142; mean age, 53±14 years) between April 2018 and March 2022. Patients for whom treatment was indicated, termed group 1, exhibited either serum alanine transaminase (ALT) and aspartate aminotransferase levels not exceeding five times the upper limit of normal and LS &gt;13 kPa, or hepatitis B virus DNA &gt;2,000 IU/mL and ALT &gt;40 IU/L. The remaining patients comprised group 2 (treatment not required). In subgroup analysis, patients with LS &lt;13 kPa were further examined. Overall, group 1 exhibited significantly higher LS (12.64±6.76 vs. 6.31±1.67 kPa, P&lt;0.001) and DS (15.52±4.95 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001) than group 2. In subgroup analysis, group 1 also demonstrated significantly higher values (LS: 8.05±2.12 vs 6.31±1.67 kPa, P&lt;0.001, DS: 13.06±2.75 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001). The areas under the curve (AUCs) for LS and DS in group 1 were 0.855 (95% confidence interval [CI], 0.80 to 0.90; P&lt;0.001) and 0.810 (95% CI, 0.75 to 0.86; P&lt;0.001), respectively. In subgroup analysis, the AUCs for LS and DS in group 1 were 0.751 (95% CI, 0.69 to 0.81; P&lt;0.001) and 0.711 (95% CI, 0.64 to 0.77; P&lt;0.001), respectively. Within group 1, the AUCs for LS and DS did not differ significantly (P&gt;0.05). LS and DS assist in classifying patients with CHB by their need for antiviral treatment.