Serum Alanine Aminotransferase Levels Research Articles

Liver Fibrosis Is Enhanced by a Higher Egg Burden in Younger Mice Infected with S. mansoni.

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10-14 years. The influence of the host's age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP+/desmin+/αSMA-) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis.

Hepatocyte activation and liver injury following cerebral ischemia promote HMGB1-mediated hepcidin upregulation in hepatocytes and regulation of systemic iron levels

We previously reported that high mobility group box 1 (HMGB1), a danger-associated molecular pattern (DAMP), increases intracellular iron levels in the postischemic brain by upregulating hepcidin, a key regulator of iron homeostasis, triggering ferroptosis. Since hepatocytes are the primary cells that produce hepcidin and control systemic iron levels, we investigated whether cerebral ischemia induces hepcidin upregulation in hepatocytes. Following middle cerebral artery occlusion (MCAO) in a rodent model, significant liver injury was observed. This injury was evidenced by significantly elevated Eckhoff’s scores and increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, total iron levels were significantly elevated in the liver, with intracellular iron accumulation detected in hepatocytes. Hepcidin expression in the liver, which is primarily localized in hepatocytes, increased significantly starting at 3 h after MCAO and continued to increase rapidly, reaching a peak at 24 h. Interestingly, HMGB1 levels in the liver were also significantly elevated after MCAO, with the disulfide form of HMGB1 being the major subtype. In vitro experiments using AML12 hepatocytes showed that recombinant disulfide HMGB1 significantly upregulated hepcidin expression in a Toll-like receptor 4 (TLR4)- and RAGE-dependent manner. Furthermore, treatment with a ROS scavenger and a peptide HMGB1 antagonist revealed that both ROS generation and HMGB1 induction contributed to hepatocyte activation and liver damage following MCAO–reperfusion. In conclusion, this study revealed that cerebral ischemia triggers hepatocyte activation and liver injury. HMGB1 potently induces hepcidin not only in the brain but also in the liver, thereby influencing systemic iron homeostasis following ischemic stroke.

Immunological, Antioxidant, Growth Responses, and Disease Resistance of Rainbow Trout, Oncorhynchus mykiss, with Feeding Diets Supplemented with Lactobacillus salivarius and Lutein

Abstract The aim of the present study was to assess the effects of dietary supplementation with Lactobacillus salivarius (LS) ATCC 11741 and lutein (LU) on immunological, antioxidant, and growth responses, and resistance against Yersinia ruckeri infection in rainbow trout (Oncorhynchus mykiss). There were seven experimental diets containing un-supplemented diet (CTL), L. salivarius at 1 × 106 (LS6) and 1 × 108 (LS8) CFU/g, lutein at 50 (LU50) and 150 (LU150) mg/kg, L. salivarius at 1 × 106 CFU/g plus lutein at 50 g/kg (LS6+LU50), and L. salivarius at 1 × 108 CFU/g plus lutein at 150 g/kg (LS8+LU150). These diets were provided to the fish (N= 735; 14.0±0.38 g). After 60 days of feeding, all experimental treatments exhibited significantly higher growth performance, compared to the CTL treatment. The intestinal protease activity and the intestinal lactic acid bacteria population in the probiotic-treated fish were significantly higher than in the CTL fish. The intestinal lipase activity was only higher in the LS6+LU50 treatment, compared to the CTL treatment. Compared to the CTL treatment, the intestinal total bacterial count, and serum superoxide dismutase significantly increased in the LS6+LU50 and LS8+LU150 treatments. The serum catalase significantly increased in LU150, LS6+LU50, and LS8+LU150 treatments, and serum glutathione peroxidase significantly increased in the lutein-treated fish. All experimental treatments, particularly LS6+LU50 and LS8+LU150, had significantly lower serum malondialdehyde levels, compared to the CTL treatment. The levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase in LU50, LS6+LU50, and LS8+LU150 treatments were significantly lower than the CTL. All experimental treatments showed significantly higher serum lysozyme (LYZ), complement, blood respiratory burst activity (RB), and skin mucus alkaline phosphatase (ALP), compared to the CTL treatment. The highest serum LYZ, C4, total immunoglobulin (Ig), blood RB activity, and skin mucus peroxidase, ALP, and Ig were observed in the LS6+LU50 and LS8+LU150 treatments. All the experimental treatments, especially LS6+LU50, exhibited significantly lower mortality after the bacterial challenge compared to the CTL. In conclusion, dietary supplementation with 1 × 106 CFU/g L. salivarius and 50 mg/kg lutein can maximally improve growth performance, digestive enzymes, antioxidant parameters, immune responses, intestinal lactic acid bacteria, and resistance against yersiniosis in rainbow trout.

Effects of including different levels of equal mix of soybean and flaxseed oils in Japanese quail diets on the growth, carcass quality, and blood biomarkers

Corn, the primary ingredient in modern poultry feeds, contains high levels of ω-6 fatty acids but lacks sufficient ω-3 fatty acids, creating an imbalance. Maintaining a balance between ω-6 and ω-3 fatty acids in poultry diets is crucial due to their competition. This study aimed to evaluate the effects of incorporating different concentrations of an equal mix of soybean oil (SO) and flaxseed oil (FO) into quail diets on growth performance, carcass quality, and blood biochemistry. One-week-old Japanese quail birds (n=200) were randomly assigned to four dietary groups, each comprising five replicates with 10 chicks per replicate. Four isonitrogenous/isocaloric basal diets were formulated. Group 1 (control) received a basal diet without SO or FO, while Groups 2-4 received basal diets supplemented with an equal mix of SO+FO at levels of 1.0%, 1.5%, and 2.0%, respectively. The inclusion of oil mixes significantly increased body weight (BW) at five weeks and daily weight gain (DWG) during weeks 3-5 and 1-5. The feed conversion ratio (FCR) improved with the addition of oil mixes throughout the trial period. Supplementing quail diets with oil mixes resulted in reduced serum total cholesterol (TC) and LDL cholesterol, elevated serum HDL cholesterol, and no significant effect on triglycerides (TG) and VLDL cholesterol levels. Quails fed oil-supplemented diets showed lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine levels, while urea and uric acid were significantly affected. Birds fed diets with oil mixes also had increased serum concentrations of immunoglobulin G (IgY), immunoglobulin M (IgM), and superoxide dismutase (SOD). However, serum immunoglobulin A (IgA), malondialdehyde (MDA), and total antioxidant capacity (TAC) levels did not significantly change across experimental groups. Overall, adding up to 2% of the SO and FO mix in growing quail feeds improved growth performance, blood lipid profile, liver and kidney function markers, immune response, and antioxidant defense. The highest level of oil mix (2%) yielded the most beneficial effects.

Effects of fermented oyster extract supplementation on free fatty acid and liver enzymes in older women with obesity.

This study aimed to investigate the effects of a 12-week intake of fermented oyster extract on free fatty acids and liver enzymes in older women with obesity and to provide basic data for improving liver function in older individuals with obesity. A randomized, double-blind, placebo-controlled clinical trial aimed to confirm the effects of fermented oyster extract intake on free fatty acid (FFA) levels and liver function in older women with obesity. The study included 40 older women with obesity with a body mass index ≥ 25 kg/m2. Participants were divided into a fermented oyster intake group (n = 20) and control group (n = 20). Serum FFA, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) levels were measured at weeks 0 and 12. Our results showed an interaction effect between the two groups in terms of serum FFA levels (p<0.05), with a post-intervention decrease in the FSO group (p<0.05). AST, ALT, and GGT levels also showed an interaction effect between the two groups (p<0.05), with a significant postintervention decrease in the FSO group (p<0.05). The intake of fermented oyster extract significantly reduced FFA, ALT, AST, and GGT levels. These results suggested that the consumption of fermented oyster extract may improve liver function. However, the findings of this study were limited to elderly women with obesity, and the relatively short intake period and small sample size may limit the generalization of the results.

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis.

Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis. Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66-0.86) and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Effect of Incorporating Soursop (Annona muricata) Leaves Powder on Reproductive Performance of Japanese Quail (Coturnix coturnix japonica)

Introduction: Soursop leaves are rich in various molecules, including total phenols, terpenes, and steroids, which possess a range of pharmacological properties that can be utilized in animal production to enhance both growth and reproduction of animals. The present study aimed to evaluate the effect of incorporating soursop (Annona muricata; A. muricata) leaves powder into feed on the reproductive performance of Japanese quail. Materials and methods: A total of 80 Japanese quails (64 females and 16 males) aged two weeks were randomly divided into four experimental groups, labeled T0, T1, T2, and T3, and received feed additives with 0 mg/kg body weight (bw), 250 mg/kg bw, 500 mg/kg bw, and 750 mg/kg bw of powdered soursop leaves, respectively. Additionally, water was provided ad libitum, and the quails' weights were measured every 7 days for a period of 75 days. At the end of the period, 12 female quails from each group were sacrificed after 24 hours fasting period. Blood was collected for hematological (Leukocyte, Erythrocyte, and Platelet indices) and serum biochemical (total serum cholesterol, total proteins, albumin, and globulin, Aspartate aminotransferase, Alanine aminotransferase, Urea, and Creatinine) analysis. The males were also sacrificed to evaluate the spermatozoa characteristics (mobility, concentration, and viability). Results: No statistical significant changes in growth characteristics or hematological parameters were observed. However, biochemical parameters increased significantly with the inclusion of Soursop (A. muricate) in quail feed, including increased total cholesterol, total protein, and globulin levels, and decreased malondialdehyde levels. This effect was most significant at dosage of 500 mg/kg bw. Serum levels of urea, Alanine aminotransferase, and Aspartate aminotransferase were not significantly affected by A. muricata whatever the concentration considered. A significant increase in fast progressive spermatozoa, along with a decrease in immotile spermatozoa, was observed with A. muricate at dosage of 500 mg/kg bw compared to the control. Sperm viability also increased significantly, particularly in live at dosage of 500 mg/kg bw. Significant increase was observed in fertility parameters, including increased fertility rate, hatchability rate of fertile eggs, total hatchability rate, and chick weight, along with decreased embryonic mortality at 500 mg/kg bw treatment compared to the control. Conclusion: In conclusion, the findings indicated that incorporating A. muricata leaf powder at 500 mg/kg bw into quail feed positively influences reproductive cells and boosts fertility growth promoters.

Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway

BackgroundThe cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear.Materials and methodsA cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI.ResultsPGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1.ConclusionsPGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Mulberry Twig Alkaloids Improved the Progression of Metabolic-Associated Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating the PGC1α/PPARα and KEAP1/NRF2 Pathways.

Background/Objectives: Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver disorders associated with obesity and metabolic syndrome, and poses a significant global health burden with limited effective treatments. The aim of this study was to assess the protective effects of mulberry twig alkaloids (SZ-A) on MAFLD and to further investigate the underlying mechanisms including the specific targets or pathways. Methods: Diet-induced obesity (DIO) and normal mouse models were established by feeding C57Bl/6J mice with a high-fat diet (HFD) or common diet for 12 weeks. SZ-A, dapagliflozin, and placebo were administered to corresponding mouse groups for 8 weeks. Data of fasting blood glucose, glucose tolerance, insulin tolerance, and the body weight of mice were collected at the baseline and termination of the experiment. Serum liver enzymes and lipids were measured by ELISA. Western blotting, qPCR, and pathological section staining were implemented to evaluate the degrees of liver steatosis, fibrosis, and oxidative stress in mice. Results: In DIO mouse models, high-dose SZ-A (800 mg/kg/d) treatment significantly inhibited HFD-induced weight gain, improved insulin tolerance, and reduced serum alanine aminotransferase, total cholesterol, and triglyceride levels compared with placebo. In DIO mice, SZ-A could alleviate the pathological changes of hepatic steatosis and fibrosis compared with placebo. Lipid catabolism and antioxidant stress-related proteins were significantly increased in the livers of the high-dose SZ-A group (p < 0.05). Inhibition of PGC1α could inhibit the function of SZ-A to enhance lipid metabolism in hepatocytes. PGC1α might interact with NRF2 to exert MAFLD-remedying effects. Conclusions: By regulating the expression of PGC1α and its interacting KEAP1/NRF2 pathway in mouse liver cells, SZ-A played important roles in regulating lipid metabolism, inhibiting oxidative stress, and postponing liver fibrosis in mice with MAFLD.

Beneficial effects of extravascular lung water index-guided volum management in patients with cardiogenic shock

Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95%CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value (AUC=0.54, 95%CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

Comparative Assessment of Beeswax Alcohol and Coenzyme Q10 (CoQ10) to Prevent Liver Aging, Organ Damage, and Oxidative Stress in Hyperlipidemic Zebrafish Exposed to D-Galactose: A 12-Week Dietary Intervention.

The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q10 (CoQ10) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ10 and 1.0% CoQ10 groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% (p < 0.001) and 41% (p < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ10 group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% (p < 0.001) and 38% (p < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ10 and 1.0% CoQ10 groups showed similar TG levels as the control, suggesting that CoQ10 supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ10 group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ10 group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.

The role of arginase estimation to predict hypertensive disorder of pregnancy at an earlier stage.

To determine the significance of serum arginase estimation as a predictor of pregnancy-induced hypertension and preeclampsia at an early stage. The observational, cross-sectional study was conducted from October 15, 2021, to October 15, 2022, at the Department of Chemical Pathology, in collaboration with the Department of Obstetrics and Gynaecology, Pakistan Railway Hospital, Islamic International Medical College Trust, Rawalpindi, Pakistan, and comprised pregnant women with 20-25 weeks of gestation who were divided into three groups. Those having no complications were placed in control group A, those with pregnancy-induced hypertension in group B, and those with preeclampsia in group C. Serum arginase, uric acid, alanine transaminase, platelet count and spot urinary protein levels were measured for each subject. Data was analysed using SPSS 26. Of the 90 women, 30(33.3%) were in group A with mean age 27.27±2.90 years, 30(33.3%) were in group B with mean age 30.17±2.48 years, and 30(33.3%) were in group C with mean age 29.33±3.11 years. There were significant intergroup differences in the mean levels of serum arginase, serum uric acid, alanine transaminase, platelet count and spot urinary protein (p<0.05). A moderate to marked increase in serum arginase levels in pregnancy-induced hypertension and preeclampsia cases, combined with abnormal serum uric acid and alanine transaminase levels along with low platelet count suggested that serum arginase estimation could be used to predict hypertensive disorders of pregnancy at an early stage.

Phase Preparation of Xiao-chai-hu Decoction and its Pharmacodynamics of Acute Liver Injury.

Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.

A Study on Serum Hepatic Enzymes in Smokers and Nonsmoker’s Adult Male

Background: Cigarette smoking is one of the greatest indirect causes of global death and disease. Cigarette smoke consists of many chemicals, including cytotoxic, carcinogenic and free radicals, therefore it affects many organs including liver either directly or indirectly. Objective: The aim of this study was to find out level of serum hepatic enzymes in smokers and non-smokers adult male. Method: This cross-sectional study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka, Bangladesh, from January 2019 to December 2019. Total study subjects were one hundred and twenty with age ranging from 20 to 50 years of male gender, selected from attendance of admitted patients and third &amp; forth class employees of Dhaka Medical College Hospital, Dhaka. Study subjects were grouped smokers as Group A and age and gender matched, nonsmokers as Group B. Group A smokers again divided into three groups. Group A1- heavy smokers (who consume 20 cigarette sticks or more per day) consist of thirty study subjects, Group A2- moderate smokers (who consume 11-19 cigarette sticks per day) consist of thirty study subjects and Group A3- light smokers (who consume 1-10 cigarette sticks per day) consist of thirty study subjects. Serum Alanine Transaminase (ALT), Aspartate transaminase (AST) and Alkaline phosphatase (ALP) level of all study subjects were estimated and recorded. Results: Mean age of the study subjects in group A1, A2, A3 &amp; B were 33.88 years, 34.60 years, 34.60 years and 29.80 years. There was a significant increase in serum ALT, AST and ALP level in heavy, moderate and light smokers when compared to nonsmokers, but the increase was more significant in heavy smokers when compared to moderate smokers, also moderate smokers when compared to light smokers. Conclusion: This study revealed that significantly higher level of serum hepatic enzymes with smokers when compared to that of non smokers. This significantly higher level was also seen in heavy smokers in comparison to moderate smokers, moderate smokers in comparison to light smokers.

Evaluation of Fasting Bile Acid Levels in Pregnant Women Diagnosed with Hyperemesis Gravidarum

Background: Hyperemesis gravidarum is a common cause of nausea and vomiting during the early gestational week. At the same time, it can also lead to an increase in liver enzyme values in patients due to or independently of underlying liver disease. This study aimed to evaluate fasting bile acid (FBA) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and urine ketone levels in pregnant women diagnosed with hyperemesis gravidarum (HG). Additionally, the study sought to investigate the relationship between HG and FBA levels. The diagnosis of HG remains primarily clinical, and identifying markers for disease severity is crucial. Methods: This retrospective cohort study obtained blood samples from 50 women diagnosed with HG and 25 healthy pregnant women. Serum levels of AST, ALT, total bilirubin (TBS), direct bilirubin, urine ketones, and FBA were measured. Statistical analysis was performed using the SPSS software version 28.0. Results: FBA levels were significantly higher in pregnant women diagnosed with HG compared to the healthy control group. Additionally, FBA levels increased simultaneously with ketonuria in the patient group. Our findings suggest that FBA levels can serve as a biomarker for diagnosing HG and indicating early-stage liver damage. Unlike previous studies, our research focused on the relationship between FBA levels and HG, providing valuable insights for future studies. Conclusions: FBA levels show promise as an objective biomarker for diagnosing HG and indicating early-stage liver damage. Further research with larger cohorts is necessary to validate these findings.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide.

To investigate the antioxidant protective effect of Lycium barbarum glycopeptide (LbGP) pretreatment on retinal ischemia-reperfusion (I/R) injury (RIRI) in rats. RIRI was induced in Sprague Dawley rats through anterior chamber perfusion, and pretreatment involved administering LbGP via gavage for 7d. After 24h of reperfusion, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) levels, retinal structure, expression of Caspase-3 and Caspase-8, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in the retina were measured. The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer (GCL) and nerve fiber layer (NFL) of rats subjected to RIRI, as shown by light microscopy and optical coherence tomography (OCT). Serum AST was higher in the model group than in the blank group (P=0.042), but no difference was found in ALT, AST, and CREA across the LbGP groups and model group. Caspase-3 expression was higher in the model group than in the blank group (P=0.006), but no difference was found among LbGP groups and the model group. Caspase-8 expression was higher in the model group than in the blank group (P=0.000), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). SOD activity was lower in the model group than in the blank group (P=0.001), and the decrease was slower in the 400 mg/kg LbGP group than in the model group (P=0.003). MDA content was higher in the model group than in the blank group (P=0.001), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model. LbGP pretreatment exhibits dose-dependent anti-inflammatory, and antioxidative effects by reducing Caspase-8 expression, preventing declines of SOD activity, and decreasing MDA content in the RIRI rat model.

Dual-factor model of sleep and diet: a new approach to understanding central fatigue.

Numerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models. Seventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed. Our findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage. We have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.

Genistein mitigates diet-induced obesity and metabolic dysfunctions in gonadectomized mice with some sex-differential effects.

Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome. Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment. Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as Fasn, Srebf1, Saa1, Cd36, Col1a1, Pck1, and Ppargc1a. Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice. Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.

Cannabinoids Used for Medical Purposes in Children and Adolescents

Cannabinoids are increasingly used for medical purposes in children. Evidence of the safety of cannabinoids in this context is sparse, creating a need for reliable information to close this knowledge gap. To study the adverse event profile of cannabinoids used for medical purposes in children and adolescents. For this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched for randomized clinical trials published from database inception to March 1, 2024, for subject terms and keywords focused on cannabis and children and adolescents. Search results were restricted to human studies in French or English. Two reviewers independently performed the title, abstract, and full-text review, data extraction, and quality assessment. Included studies enrolled at least 1 individual 18 years or younger, had a natural or pharmaceutical cannabinoid used as an intervention to manage any medical condition, and had an active comparator or placebo. Two reviewers performed data extraction and quality assessment independently. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and PRISMA-S guideline were used. Data were pooled using a random-effects model. The primary outcome was the incidence of withdrawals, withdrawals due to adverse events, overall adverse events, and serious adverse events in the cannabinoid and control arms. Secondary outcomes were the incidence of specific serious adverse events and adverse events based on organ system involvement. Of 39 175 citations, 23 RCTs with 3612 participants were included (635 [17.6%] female and 2071 [57.3%] male; data not available from 2 trials); 11 trials (47.8%) included children and adolescents only, and the other 12 trials (52.2%) included children, adolescents, and adults. Interventions included purified cannabidiol (11 [47.8%]), nabilone (4 [17.4%]), tetrahydrocannabinol (3 [13.0%]), cannabis herbal extract (3 [13.0%]), and dexanabinol (2 [8.7%]). The most common indications were epilepsy (9 [39.1%]) and chemotherapy-induced nausea and vomiting (7 [30.4%]). Compared with the control, cannabinoids were associated with an overall increased risk of adverse events (risk ratio [RR], 1.09; 95% CI, 1.02-1.16; I2 = 54%; 12 trials), withdrawals due to adverse events (RR, 3.07; 95% CI, 1.73-5.43; I2 = 0%; 14 trials), and serious adverse events (RR, 1.81; 95% CI, 1.21-2.71; I2 = 59%; 11 trials). Cannabinoid-associated adverse events with higher RRs were diarrhea (RR, 1.82; 95% CI, 1.30-2.54; I2 = 35%; 10 trials), increased serum levels of aspartate aminotransferase (RR, 5.69; 95% CI, 1.74-18.64; I2 = 0%; 5 trials) and alanine aminotransferase (RR, 5.67; 95% CI, 2.23-14.39; I2 = 0%; 6 trials), and somnolence (RR, 2.28; 95% CI, 1.83-2.85; I2 = 8%; 14 trials). In this systematic review and meta-analysis, cannabinoids used for medical purposes in children and adolescents in RCTs were associated with an increased risk of adverse events. The findings suggest that long-term safety studies, including those exploring cannabinoid-related drug interactions and tools that improve adverse event reporting, are needed.

Comparative study of Indocyanine Green fluorescence imaging versus conventional fiber-optic imaging in laparoscopic choledochotomy for stone extraction and immediate biliary incision suturing.

To explore the Advantages of Indocyanine Green (ICG) Fluorescence Imaging over Conventional Fiber-Optic Imaging in Laparoscopic Cholangiography and Immediate Suture for Stone Removal. The study is a randomized controlled descriptive research. Consecutive patient data were collected from October 2022 to January 2024 at the Second People's Hospital of Chengdu for those who underwent laparoscopic bile duct exploration and stone removal, totaling 72 cases. According to the order of admission, they were randomly assigned to either the study group or the control group, with 36 cases in each group. Ten minutes preoperatively, indocyanine green (ICG) was administered intravenously through a peripheral vein to the subjects in the study group, to enable real-time fluorescent tracing of the extrahepatic bile ducts during surgery. This study compares the efficiency of bile duct structure and boundary recognition, the timeliness of bile duct incision positioning, operative time, blood loss, and the incidence of bile duct injury between patients who were injected with ICG and those who were not. In addition, it assesses liver function and white blood-cell counts rechecked 24h postoperatively, the duration of postoperative hospital stay, and the occurrence of bile leakage. The study included 72 patients, with 36 in the indocyanine green (ICG) fluorescence group and 36 in the conventional fiber-optic group, comprising 26 males and 46 females. There were 18 patients with a history of previous biliary exploration surgery and 23 who had undergone previous cholecystectomy. During surgery, ICG fluorescence was successfully visualized in all 36 cases of the ICG group, allowing for a clear view of the anatomical structure and boundaries of the extrahepatic bile ducts. Compared to the control group, the ICG fluorescence group demonstrated a reduction in the time required for identification of the biliary system and positioning of the bile duct incision, as well as a decrease in operative time and postoperative hospital stay; intraoperative blood loss and the incidence of bile leakage were also relatively reduced, with statistically significant differences (P < 0.05). However, there were no statistically significant differences in postoperative serum alanine aminotransferase levels, white blood-cell counts, direct bilirubin, and indirect bilirubin between the two groups (P > 0.05). One case of bile duct injury occurred in the control group. The application of ICG fluorescence navigation in laparoscopic cholecystectomy can effectively enhance the visibility of the bile ducts, rapidly identify the location for bile duct incision, and is conducive to reducing both the duration of surgery and postoperative hospital stay. It also minimizes intraoperative blood loss, prevents bile leakage and bile duct injuries. This program has demonstrating significant clinical value.