AST Levels Research Articles

Genetic inhibition of nicotinamide N-methyltransferase and prevention of alcohol-associated fatty liver in humans.

Recent studies of animal models reported Nicotinamide N-methyltransferase (NNMT) as a potential therapeutic target for preventing alcohol-associated fatty liver (AFL), yet its efficacy and safety in humans remain unknown. We aim to estimate the effectiveness and safety of inhibiting NNMT in humans. We leveraged Electronic Medical Records (EMRs) data coupled with genetic information to perform a retrospective drug target validation study. We examined longitudinal clinical data from 612 individuals with excessive alcohol consumption. Two variants lowering NNMT protein levels were combined to calculate a weighted NNMT genetic score that could mimic mild inhibition of NNMT. Participants with an NNMT score above the median were classified as genetically inhibited, while others were considered non-inhibited. We then evaluated whether genetic inhibition of NNMT would affect the incidence of AFL or the risk of liver injury, to illuminate the effectiveness and safety of genetic inhibition of NNMT respectively. NNMT genetic inhibition correlated with a reduced AFL risk (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.49-0.90, P = 0.009) without a significant increase in serum aminotransferase levels (P > 0.10). Notably, elevated ALT and AST levels were observed (P < 0.05) in the genetically inhibited group prior to alcohol exposure. These findings suggest NNMT inhibition is a promising avenue for AFL prevention among individuals with excessive alcohol intake. They also underscore the need for precise target population identification to mitigate potential adverse effects.

PHYTOCHEMICALS ANALYSIS AND TOXICITY STUDIES OF ETHANOL LEAVES EXTRACT OF AZADIRACHTA INDICA, ANACARDIUM OCCIDENTALE, AND MORINGA OLEIFERA IN RATS

Medicinal plants have importance medicinal properties and pharmacological activities. Medicinal value and pharmacological activities of plants are attributed to their bioactive constituents. The efficacy of medicinal plants could not only be considered but also their safety for consumption. The phytochemicals analyses were performed using standard methods. Toxicity tests were conducted using Lorke’s method. The ethanol leaves extract of Azadirachta indica, Anacardium occidentale, and Moringa oleifera contain several phytochemicals. The LD50 value of ethanol leaves extract of Azadirachta indica, Anacardium occidentale, and Moringa oleifera was 3807.89 mg/kg, 4505.55 mg/kg, and above 5000 mg/kg, respectively. The ethanol leaves extract of Anacardium occidentale and Azadirachta indica demonstrated an increase in the levels of ALT, AST, total bilirubin, and globulin, while the Moringa oleifera exhibited a decrease in the levels of ALT, AST, and total bilirubin coupled with increase in total protein and albumin levels. The administration of ethanol leaves extract of Anacardium occidentale and Azadirachta indica increased the levels of urea, creatinine, sodium, potassium, calcium, chlorides, and HCO3- while decreased by the administration of the ethanol leaves extract of Moringa oleifera in rats. The ethanol leaves extract of Azadirachta indica and Anacardium occidentale demonstrated significant decrease in RBC count and PCV while Moringa oleifera exhibited significant increase in RBC count and PCV. Hemoglobin content was significantly decrease by the ethanol leaves extract of Azadirachta indica. The presence of these bioactive metabolites implies that the plants have medicinal properties. The ethanol leaves extract of Moringa oleifera at 5000 mg/kg dose is relatively non-toxic and safe for gavage administration while ethanol leaves extract of Azadirachta indica and Anacardium occidentale are slightly toxic for oral administration.

Non-invasive predictors of the first episode of bleeding from esophageal varices in patients with liver cirrhosis awaiting transplantation

Background. To date, various non-invasive techniques or tests have been proposed that can identify a high risk of bleeding from esophageal varices. Despite a significant number of studies revealing the presence of venous varices as a likely factor for the development of bleeding due to their rupture, data on predictors of the first episode of bleeding are few and often contradictory.Objective. To determine non-invasive independent predictors of the first episode of bleeding in patients waiting for liver transplantation.Material and methods. A comparative retrospective study was conducted in 729 patients with decompensated cirrhosis who were on the waiting list for liver transplantation. We analyzed demographic, clinical and laboratory parameters, MELD-Na, Child-Turcotte-Pugh scores, FIB-4 Index, APRI, AST/ALT ratio; we determined the liver stiffness, spleen diameter, studied the liver stiffness-spleen diameter to platelet ratio risk score (LSPS model), platelet count/spleen diameter ratio in the groups of patients with the first episode of bleeding (n=334) and without it (n=395). The accumulated risks in the compared groups were assessed using a model of proportional hazards (Cox regression) in univariate and multivariate analysis.Results. During 48 months of follow-up from the time of patient placement on the liver transplant waiting list, primary bleeding events developed in 45.8%. The risk of developing the first episode of bleeding progressively increased with LSPS &gt;3.5 and reached maximum values in patients awaiting liver transplantation within 48 months of inclusion in the waiting list, while with LSPS &lt;3.5 the risk was minimal.Conclusion. Independent non-invasive predictors of the first episode of bleeding are a high level of AST, a high fibrosis index (FIB-4), a decrease in the ratio of platelet count/spleen diameter and a high LSPS value. Their application in clinical practice will improve the results of dispensary and screening examinations of patients with portal hypertension.

Electrolyte imbalance and liver function test abnormalities among pregnant women with hyperemesis gravidarum at Wag-himra zone public hospitals, Northeast Ethiopia, 2023: a comparative cross-sectional study

BackgroundHyperemesis gravidarum affects about 4.8% of pregnant women. It can lead to electrolyte imbalances and liver function disturbances, which may result in pregnancy complications. Despite its prevalence, data on these abnormalities in the study area is scarce. Therefore, the current study investigated these health concerns among HG-affected pregnant women in this region from June to October 2023.MethodA comparative cross-sectional study was conducted on 123 study participants. Socio-demographic, clinical, and anthropometric data were collected using structured questionnaires. Blood samples were taken to determine liver function tests and electrolyte levels. Statistical analysis was performed using a one-way ANOVA with a Tuckey post hoc test, Kruskal-Wallis with a Mann–Whitney U test, and binary logistic regression analysis. A p-value of &amp;lt;0.05 with 95% confidence intervals was considered statistically significant.ResultsThe results showed that pregnant women with hyperemesis gravidarum had significantly higher levels of AST and ALT and lower levels of Na+ and K+ compared to normal pregnant women and non-pregnant women. The abnormalities observed were elevated AST (48.8%), ALT (46.3%), and decreased Na+ (51.2%) and K+ (41.5%). Hyperemesis gravidarum was associated with both electrolyte imbalances and liver function test abnormalities.ConclusionPregnant women with hyperemesis gravidarum experience electrolyte imbalances and liver function test abnormalities. Given the marked increase in liver enzymes and decrease in electrolyte levels, the authors recommend routine laboratory testing of liver function and electrolyte parameters for pregnant women with hyperemesis gravidarum is recommended.

Impact Of Fragrant Pandan Leaves Ethanol Extract (Fplee) On Alt And Ast Levels In High-Fat Diet-Induced Rat

Energy-dense, low-nutrient, and ultra-processed diets rich in fat can be a risk factor for fatty liver disease. Fragrant pandan is a plant that grows widely in Indonesia and is widely used as a herbal plant. This study aimed to determine the potential of fragrant pandan leaf ethanol extract (FPLEE) to reduce ALT and AST levels. It is a posttest control group design experiment. A total of 24 Rattus norvegicus specimens. All groups were given high-fat food for two weeks, except for NC. In the next two weeks, S was induced by simvastatin and FPLEE; T1, T2, and T3 were induced by 8, 16, and 32 mg/200 g BW/day, respectively. The One-Way ANOVA test results showed α=0.000 for ALT and α=0.029 for AST. Post-hoc LSD showed that NC was significantly different from T1, T2, and T3 (p0.05); therefore, FPLEE was unable to reduce ALT levels. For AST levels, NC was significantly different from C+, T1, and T2 (P0.05). Thus, T3 (32 mg/200 g BW/day of FPLEE) yielded the best results in reducing AST levels (p0.05). Based on these results, FPLEE has side effects on liver function, as seen in increased blood ALT levels, but it can reduce blood AST levels.

Hypolipidemic Effects of Eryngium Caucasicum Leaves Extract on Rats with Induced Diabetes Mellitus

Research Article AJVS. 2024; 17(2): 1-7doi: 10.37940/AJVS.2024.17.2.1 Hypolipidemic Effects of Eryngium Caucasicum Leaves Extract on Rats with Induced Diabetes Mellitus Glaucio Dire Feliciano. Abstract This research aimed to assess the hypolipidemic effects of an extract from Eryngium caucasicum in a Rat model of Type 2 Diabetes Mellitus produced by Streptozotocin. Forty adult male Wistar rats were divided into five groups, with a total of eight rats in each: (1) healthy control rats, (2) diabetic rats with no diabetes, (3) diabetic rats given insulin, (4) diabetic rats given 200 mg/kg orally for 30 days of Eryngium caucasicum extract, and (5) diabetic rats given 300 mg/kg orally for 30 days. Injecting Nicotinamide and Streptozotocin intraperitoneally caused diabetes. Fasting blood sugar, hepatic enzymes, and lipid profiles were determined from blood samples taken after the trial. The levels of HDL were increased significantly in G3, G4, and G5 compared to G2. The insulin group and the group given 300 mg/kg of Eryngium caucasicum substantially reduced LDL cholesterol compared to the G2. It should be mentioned that the diabetic control group had higher TC compared to the healthy control group after rat diabetes induction (P = 0.020). Compared to the G2, G3 treated with insulin and groups treated with extract at dosages of 200 as well as 300 mg/kg body weight had a substantially lower TC (P &lt; 0.01). Serum TG was improved when insulin and Eryngium caucasicum extract were administered at 200 and 300 mg/kg dosages, respectively (P &lt; 0.05). Serum ALT and AST levels were shown to be elevated after STZ diabetes induction as compared to the G1. Even though diabetic rats' ALT and AST levels were enhanced by insulin and all 2 plant trial dosages, 200 and 300 mg/kg. In summary, our findings suggest that the antidiabetic, hypolipidemic, and hepato-protective properties of Eryngium caucasicum, when administered to an animal model of Type 2 diabetes mellitus, may vary with dosage.

Simplified ischemia-free liver transplantation by providing alternating flow of the portal vein and hepatic artery: Applicability, efficiency, safety.

Conventional ischemia-free liver transplantation (CIFLT) represents a pioneering procedure that circumvents ischemia-reperfusion injury (IRI) to livers throughout the transplant procedure. However, its complexity has limited its widespread adoption. This study introduced a simplified ischemia-free liver transplantation (SIFLT) technique by providing alternating flow of the portal vein and hepatic artery, demonstrating its efficacy and safety. In this retrospective study, 32 patients who received SIFLT and 32 who received CIFLT were included between January 2021 and January 2024. The intraoperative and postoperative outcomes were collected and elevated. Patients who underwent SIFLT had a shorter anhepatic phase (44.0±2.4 mins vs 51.6±2.4 mins, p=0.03), along with a comparatively reduced intraoperative blood loss compared to those underwent CIFLT. Furthermore, the SIFLT group exhibited significantly lower peak AST levels within postoperative 7 days (413.1±62.6U/L vs 707.5±110.7U/L, p=0.02). The incidence of early allograft dysfunction, primary non-function, transplant-related complications were similar across both groups. There were no significant differences in number of Clavien-Dindo classification of surgical complication and comprehensive complication index at 3-month after transplantation. Kaplan-Meier analysis confirmed similar patient and graft survival rates. The subgroup analysis of extended criteria donors demonstrated that SIFLT can effectively reduce anhepatic phase and intraoperative blood loss, and can achieve clinical prognosis similar to CIFLT. Additionally, histological analysis revealed that both groups demonstrated well-preserved liver and bile duct. The SIFLT simplifies the intricate surgical procudure while ensuring protection of livers from IRI. This technique holds promise for enabling patients to achieve clinical outcomes comparable to those of CIFLT.

A combined association of alanine aminotransferase, aspartate transaminase and bilirubin with sleep duration in aged 16-85 years (2005-2010).

Sleep is a vital restorative process that plays a pivotal role in maintaining the delicate equilibrium of mental and physical well-being. Both short and long sleep duration are associated with a range of adverse health outcomes. Numerous studies have consistently demonstrated a robust association between sleep duration and liver disease. In this study, we conducted statistical tests and performed subgroup analyses to explore potential variations in this association across different contexts, aiming to elucidate the correlation between ALT, AST, and TB with sleep duration. This cross-sectional investigation utilized datasets from the National Health and Nutrition Examination Survey 2005 to 2010. Multivariate linear regression models were used to examine the linear association between ALT, AST, and TB with sleep duration. Test for interaction is commonly conducted using multivariabte models to assess statistically significant subgroup disparities. Fitted smoothied curves and threshold effect analyses were employed to depict nonlinear relationships. The study enrolled 17,491 participants aged 16 to 85 years who met the inclusion and exclusion criteria, with a mean age of the participants was 45.58 ± 19.94 years. Multivariate linear regression analysis showed a significant positive association between sleep duration and ALT [-0.23 (-0.45, -0.00) 0.0455] and AST[-0.20 (-0.38, -0.01) 0.0338] in Model 3. Using a two-segment linear regression model, we found an U-shaped relationship and significant inflection point between between ALT and AST with sleep duration. The present study unveiled a significant inverse correlation between sleep duration and levels of ALT and AST, while no significant association was observed with TB levels. Furthermore, variations in the optimal sleep duration for liver function recovery were identified across diverse populations, thereby offering valuable healthcare recommendations to public.

Evaluation of the Hypoglycemic Activity of Methanolic Extract of Foeniculum Vulgare in Streptozotocin-induced Diabetic Wistar Rats.

This study aimed to assess the hypoglycemic effects of methanolic extract of Foeniculum vulgare in male Wistar rats that were diabetic due to streptozotocin. Experimental diabetes was initially induced in male Wistar rats by intravenous injection of streptozotocin (55 mg/kg). Subsequently, the rats received daily oral administration of the methanolic extract of Foeniculum vulgare (250 mg/kg) and the standard drug metformin (300 mg/kg) for 28 days. Furthermore, a tolerance test was carried out. The study findings suggest that the diabetic rats in the untreated control group showed hyperglycemia and significant weight loss, as well as polydipsia, polyphagia, and polyuria. However, rats treated with methanolic extract of Foeniculum vulgare for 28 days showed a significant reduction in blood glucose levels and a marked improvement in body weight. Additionally, there was a notable decrease in the daily rate of food consumption and water intake and a significant reduction in serum glucose level, triglycerides, total cholesterol, creatinine, urea, AST, and ALT levels compared to the untreated diabetic control group. Histopathological examination revealed that after 28 days of treatment with 250 mg/kg of methanolic extract of the Foeniculum vulgare, the size of the islets of Langerhans in the pancreas tissue was decreased. Moreover, liver tissue demonstrated normalization with a normal central lobular structure, and kidney tissue showed normalization with a normal Bowman's capsule. These findings suggest that the methanolic extract of Foeniculum vulgare can potentially treat diabetes and should be evaluated further for drug development.

Antiplasmodial Potentials, Phytocompounds and the Possible Toxic Effects of Administration of Ethylacetate Extract of Spondias mombin Linn.

Malaria, caused by Plasmodium parasites, is a global health concern. Natural products, such as plant extracts, are investigated for new antimalarial agents. Spondias mombin, traditionally used for medicinal purposes, was examined for its effects on parasitemia, haematological parameters, antioxidant activities, liver function biomarkers, and serum electrolytes in Plasmodium berghei-infected mice. Mice received varying doses of the ethylacetate extract. Various dosages of the extract and the prescribed medication dramatically slowed the parasite's growth. The extract significantly improved red blood cell (RBC) and platelet counts, particularly at higher doses. Hemoglobin levels were decreased dose-dependently. Antioxidant analysis showed increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced catalase (CAT) activities and malondialdehyde (MDA) levels, indicating robust antioxidant properties. Liver function tests showed mixed effects, with elevated AST, ALP, and TB levels at some doses, yet decreased ALT at the highest dose, suggesting possible hepatoprotective effects. Serum electrolyte levels remained stable. Seventy-eight (78) bioactive components were identified in the extract by GC-MS analysis. The extract demonstrated substantial antimalarial and antioxidant capacities, with minimal liver stress and stable electrolyte levels, suggesting safety as an adjunct therapy for malaria. Further research is needed to ascertain the specific antimalarial bioactive constituents and their mechanisms of action.

Combinatorial Treatment with Praziquantel and Curcumin Reduces Clonorchis sinensis Parasite Burden and Clonorchiasis-Associated Pathologies in Rats

Background/Objectives: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug. Here, we evaluated the effect of CUR+PZQ combinatorial drug treatment on C. sinensis infection as well as its effect on ameliorating fibrotic tissue damage in rats. Methods: Worm viabilities following CUR and PZQ treatments were confirmed through microscopy and tetrazolium salt absorption. Anthelminthic effect and hepatobiliary damage mitigation in rats were determined by quantifying worm recovery, histopathological staining, and enzyme-linked immunosorbent assay. Results: CUR+PZQ at LD50 doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with C. sinensis, and drugs were administered at 1 and 4 weeks post-infection (wpi) to assess drug-induced changes in worm burden. Significant reductions in worm burden recoveries were observed following CUR+PZQ treatment at both time points, accompanied by markedly reduced serum and mucosal IgG responses. ALT and AST levels were also substantially lower in combinatorial drug treatment groups than controls. Histopathological examinations confirmed that parasite-induced bile duct lumen widening and liver fibrosis were suppressed at 1 wpi, implying that CUR+PZQ co-treatment can alleviate clonorchiasis-associated pathologies. Conclusions: Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis.

Protective effects of nutrients and antioxidant-rich seed oil and sprouted seed oil of Benincasa hispida against formaldehyde-induced hepatic and renal damage

IntroductionIn traditional Chinese medicine (TCM), Benincasa hispida, commonly referred to as wax gourd, winter melon, or ash gourd, has been used extensively for managing fever, urinary dysfunction, cough with viscous mucus, pulmonary and periappendicular abscesses, edema, spermatorrhea, gonorrhea, discharge pus, and expel dampness. In this study, we investigated the antioxidant, macro- and micronutrients as well as the protective effects of Benincasa hispida seed oil (BHSO) and sprouted seed oil (BHSSO) against formaldehyde (FA)-induced liver and kidney damage in mice. MethodsThe in vitro antioxidant activity was evaluated using the DPPH radical scavenging assay. Protein, fat, fiber, and total carbohydrate contents were assessed, and micronutrients were determined using flame atomic absorption spectrophotometry. BHSO, BHSSO, and Vitamin E (3485 mg/kg, 3485 mg/kg, and 30 mg/kg p.o., respectively) were administered once daily shortly after formaldehyde exposure (10 mg/kg, I.P.) to separate groups of Swiss albino male mice for a period of 26 days to investigate their protective effects against hepatic and renal damage. The normal control group was given access to sterile tap water and a balanced diet, whereas the disease control group was given only 10 mg/kg of formaldehyde intraperitoneally. Results and DiscussionSerum ALT, AST, and creatinine levels were significantly elevated after formaldehyde (FA) administration. Histopathological examinations of liver and kidney tissue revealed degenerative changes in both organs. However, mice pretreated with BHSO and BHSSO showed a significant reduction in FA-induced elevations of serum ALT, AST, and creatinine levels and retained normal liver and kidney tissue histology. BHSO and BHSSO exhibited the ability to scavenge free radicals, as shown in vitro antioxidant studies. Essential micronutrients like zinc (Zn), copper (Cu), calcium (Ca), and chromium (Cr) were also found in both oils. These micronutrients may prevent the inactivation of antioxidant enzymes, thereby increasing free radical scavenging and preserving oxidation and antioxidant equilibrium. Moreover, both oils were found to contain crude fat and carbohydrates that are essential in safeguarding against formaldehyde-induced hepatic and renal damage by offering structural and metabolic support to cells and preserving membrane integrity. ConclusionBenincasa hispida seed oil and sprouted seed oil have significant protective effects against formaldehyde-induced hepatic and renal damage and serve as a valuable source of antioxidants, as well as macro- and micronutrients.

Anti-hyperuricemic effects of the seeds of Hovenia acerba in hyperuricemia mice

Ethnopharmacological relevanceThe seeds of Hovenia acerba water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA). Aim of the studyTo evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms. Materials and methodsThe anti-HUA effects were evaluated on a mouse model by testing HAW’s effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways. ResultsHAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved. ConclusionHAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.

Role of Hepatic and Renal Biomarkers in Diagnosing Preeclampsia

Objective: The study aims to gain insight into the importance of hepatic and renal biochemical parameters AST, ALT, bilirubin, urea, creatinine, urinary protein to creatinine ratio, and novel marker cystatin C in the domain of preeclamptic patients. Methodology: This prospective cohort study was conducted in Central Park Medical College and Teaching Hospital Lahore from Sep 2023 to Apr 2024 on 300 subjects. Inclusion criteria were pregnant women over 18 years of age, gestational age of 20 weeks, and singleton pregnancy. Women with preexisting hypertension, kidney disease, or other diseases causing liver dysfunction were excluded. Blood and urine samples were collected to measure AST, ALT, bilirubin, urea, creatinine, urinary protein to creatinine ratio, and novel marker cystatin C and data was analysed using an independent t test and Chi-square test by SPSS version 26. Results: ALT, AST, and bilirubin levels were higher (45±12 p&lt;0.001, mean±SD 55±15 U/L, mean±SD: 1.5±0.4 mg/dL) in preeclamptic women. Creatinine, urine protein to creatinine ratio, and cystatin C (mean±SD: 1.0±0.2 mg/dl, mean±SD: 300±100 mg/g, p 1.2±0.3ng/mL) were raised in preeclamptic women as compared to the control group. Conclusions: Serum creatinine, urine protein/creatinine ratio, and cystatin C and creatinine were found in women with preeclampsia compared to women without preeclampsia.

Effects of single or conjoint administration of poly-β-hydroxybutyrate and Bacillus subtilis on growth, antioxidant capacity and apoptosis of common carp (Cyprinus carpio)

This study aims to assess single or conjoint administration of poly-β-hydroxybutyrate (PHB) and Bacillus subtilis on growth, the function and morphology of hepatopancreas and intestines, antioxidant capacity, inflammation and apoptosis in common carp (Cyprinus carpio). In this study, four diets were formulated according to a 2 × 2 factorial design, including control diet (without PHB and B. subtilis), B. subtilis diet (with 1 × 108 CFU/g B. subtilis), PHB diet (4%PHB) and PHB+B. subtilis diet (with 4%PHB and 1 × 108 CFU/g B. subtilis). Common carp (3.50 ± 0.03g) were allocated into 4 groups (3 replicates per group, 30 fish per replicate) and fed for 8 weeks. Results demonstrated that single or conjoint administration of 4%PHB and 1 × 108 CFU/g B. subtilis promoted the growth performance and feed utilization, with interaction (P<0.05). 4%PHB and 1 × 108 CFU/g B. subtilis increased the levels of protease in intestines, lipase and amylase in hepatopancreas and intestines, AST and ALT in hepatopancreas, intestinal permeability (DAO, D-LA, 5-HT and ET-1), intestinal tight junction protein-related mRNA, intestinal growth indexes (fold height and muscular layer thickness), antioxidant capacity (CAT, T-AOC, T-SOD and GSH-PX in hepatopancreas and intestines, Nrf2, SOD, CAT and GSH-PX mRNA in hepatopancreas and intestines, HO-1 mRNA in hepatopancreas), anti-inflammatory and anti-apoptosis (TGF-β, IL-10 and Bcl-2 mRNA in hepatopancreas and intestines) (P<0.05), decreased the levels AST and ALT in serum, intestinal growth indexes (lamina propria width), oxidative stress indicator (MDA) and Keap1 mRNA in hepatopancreas and intestines, pro-inflammatory and pro-apoptosis (NF-κB, TNF-α, IL-1β, IL-6, Bax, Caspase-3, Caspase-8 and Caspase-9 mRNA in hepatopancreas and intestines) (P<0.05), improved the morphology of hepatopancreas and intestines. Whereas the levels of protease in hepatopancreas were only increased by 1 × 108 CFU/g B. subtilis (P<0.05), the levels of HO-1 mRNA in intestines were only up-regulated by 4%PHB (P<0.05). Furthermore, the interaction between 4%PHB and 1 × 108 CFU/g B. subtilis was discovered for the levels of AST, ALT and 5-HT in serum, intestinal Occludin mRNA, MDA in hepatopancreas and intestines, Keap1, HO-1 and IL-1β mRNA in hepatopancreas, GSH-PX mRNA in hepatopancreas and intestines, Bcl-2 and Caspase-3 mRNA in intestines (P<0.05). In conclusion, this study indicated that conjoint administration of 4%PHB and 1 × 108 CFU/g B. subtilis had synergistic promotion on the growth performance, digestive function, antioxidant capacity, hepatopancreatic and intestinal functions of common carp.

Therapeutic Potential of Aloe vera and Aloe vera-Conjugated Silver Nanoparticles on Mice Exposed to Hexavalent Chromium.

Hexavalent chromium (Cr (VI)) is a hazardous heavy metal that induces hepatotoxicity and nephrotoxicity. Thus, this study was planned to explore the ameliorating capacity of Aloe vera leaf gel extract (AV) and their conjugated silver nanoparticles (AVNP) against Cr (VI) induced hepatotoxicity and renal toxicity. The organ indices, level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total protein, and creatinine in blood serum were measured. The histopathological and micrometric analysis of the hepatic and renal tissue sections were studied. The hepatosomatic index was raised significantly (0.098 ± 0.13g) in Cr treated group. The blood serum level of AST (484 ± 10.7 U/L), ALT (163 ± 5.5 U/L), ALP (336.7 ± 9.5 U/L), MDA (642.3 ± 28.3 U/L), and creatinine (4.0 ± 0.1mg/dL) were increased significantly, whereas total protein level was declined (2.8 ± 0.3g/dL) significantly in Cr exposed group. In the histopathological study, necrosis, disturbed hepatic cords, impaired glomeruli, and Bowman's capsule were noted. Micrometric data from the liver and kidney revealed a significant surge in the size of hepatocytes and their nuclei (1188.2 ± 467.7µ2 and 456.5 ± 205.6µ2) and CSA of glomeruli and Bowman's capsule (9051.8 ± 249.8µ2 and 11,835.5 ± 336.7µ2) in Cr (VI) exposed group, whereas the brush border (10.2 ± 4.0µ) size declined significantly. The administration of AV and AVNP reduced the oxidative stress induced by Cr (VI).

Predictors of Significant Fibrosis Among People Living with HIV with Metabolic Dysfunction- Associated Steatotic Liver Disease

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among people living with HIV (PLWH) due to comorbidities and factors related to HIV infection. This study aimed to identify clinical predictors of significant fibrosis among PLWH with MASLD. Materials and Methods: A retrospective cohort study was conducted with PLWH having CD4 counts ≥200, enrolled between April and October 2023 at two tertiary hospitals. The primary outcome was identifying the clinical predictors of significant fibrosis (F≥2) defined by TE≥8 kPa. Secondary outcomes included MASLD prevalenceand characteristics. Results: Among 96 PLWH, 52 (54.2%) had MASLD. The mean age was 49.7±8.0 years, 63.5% were male, and the mean BMI was 25.8±4.1 kg/m². Obesity, diabetes, and dyslipidemia were present in 17.3%, 19.2%, and 46.2% of participants, respectively. The mean CAP and TE were 285±36 dB/m and 8.7±7.8 kPa, respectively. Significantfibrosis was present in 24 patients (46.2%). Fibrosis scoring systems (FIB-4, APRI, NFS) demonstrated good accuracy (AUROCs: 0.84, 0.85, 0.76, respectively). Multivariate analysis identified predictors of significant fibrosis: higher BMI (aOR 1.24, p=0.042), dyslipidemia (aOR 3.96, p=0.038), and higher AST (aOR 1.19, p=0.011). The AGA pathway using two steps (FIB-4 and TE) improved reclassification of significant fibrosis risk, reducing the number of individuals at indeterminate risk, 12 out of 52 in the first step to 7 out of 52 in the second step. Conclusion: MASLD is highly prevalent in PLWH, with about half experiencing significant fibrosis. Predictors of significant fibrosis include dyslipidemia, higher BMI, and elevated AST levels. Fibrosis scoring systems accurately predict significant fibrosis.

Efficacy and safety of the FGF19 analog aldafermin for the treatment of nonalcoholic steatohepatitis: a GRADE assessed systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is increasingly concerning due to its rising prevalence. It encompasses conditions from simple steatosis to severe nonalcoholic steatohepatitis (NASH), posing risks such as fibrosis, cirrhosis, or hepatocellular carcinoma if untreated. This systematic review and meta-analysis aims to assess aldafermin, an FGF19 analog, for efficacy and safety in NASH patients. Eligible studies were identified by searching PubMed, Cochrane Library, and Google Scholar, resulting in 1115 studies. Three RCTs were included. The risk of bias was assessed using the Cochrane Risk of Bias tool, and data synthesis utilized Review Manager software. The certainty of evidence was evaluated with the GRADE approach. In the 3mg dose group, aldafermin significantly improved various parameters. The ELF score decreased notably (pooled MD: -0.46, 95% CI: -0.64 to -0.28; P<0.00001). Additionally, fibrosis improvement without NASH worsening showed a pooled MD of 8.15 (95% CI: -3.62 to 19.93; P<0.17), and fibrosis improvement with NASH resolution displayed a pooled MD of 10.16 (95% CI: 1.68-18.64; P=0.02). Furthermore, significant reductions were noted in absolute AST levels (pooled MD: -13.40, 95% CI: -18.66 to -8.14; P<0.00001) and absolute ALT levels (pooled MD: -19.92, 95% CI: -27.08 to -12.75; P<0.00001), suggesting improved liver function. The meta-analysis indicates that aldafermin, particularly, the 3mg dose, shows significant efficacy in improving liver histology and biochemical markers in NASH patients compared to placebo, along with a satisfactory safety profile.

Lutein protection against doxorubicin-induced liver damage in rats is associated with inhibition of oxido-inflammatory stress and modulation of Beclin-1/mTOR activities.

A wide range of clinical applications are reported for doxorubicin (DOX), yet both people and research animals experience substantial tissue damage. However, the protective mechanism of lutein, a natural carotenoid against doxorubicin associated liver toxicity has not been fully studied. Therefore, the aim of this study is to investigate the protective mechanism of lutein in doxorubicin-induced liver damage. Twenty male Wistar rats were randomly assigned to four groups and treated as follows: group 1 was administered 10-ml/kg body weight of normal saline intraperitoneally for a duration of 28days. Group 2 was administered doxorubicin (15-mg/kg body weight) intraperitoneally for 3days in a row. Group 3 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28days, and group 4 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28days with last 3days in a row (days 26, 27, and 28) of doxorubicin injection (15-mg/kg body weight). Our results showed that lutein reduced levels of AST, ALT, ALP, LDH, MDA, nitrite, beclin-1, caspase-3, IL-6 as well as TNF-α against the increase caused by doxorubicin. GSH, SOD, GST, catalase, mTOR as well as Bcl-2 were markedly increased by lutein against the harmful effect of doxorubicin. Moreso, lutein restored normal histoarchitecture as well as reduced fibrosis. In conclusion, lutein protection against doxorubicin-induced liver damage in male Wistar rat is associated with inhibition of oxidative stress, pro-inflammatory reactions, and modulation of Beclin-1/mTOR activities.

Comparative Effects of Crocin and Losartan on RAGE, TGF-β, TNF-α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes.

AGEs, via RAGE, increase the development of hyperglycemia-induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF-α and TGF-β gene expression in diabetic rats, as well as histological changes in liver tissue. Diabetes was induced in 40 male Wistar rats using Streptozotocin (50 mg/kg, IP). There were five groups of rats: diabetic and healthy groups, diabetic rats given crocin (50 mg/kg), losartan (25 mg/kg) and both (crocin + Los). Serum glucose, ALT and AST levels were measured 4 weeks later. qPCR was used to examine the TNF-α, TGF-β and RAGE gene expression in liver tissue. Crocin was found to be effective in lowering FBG in the diabetes group. The serum levels of ALT and AST decreased in all treated groups, but this decrease was significant in the crocin + Los group (p < 0.05). The relative expression of RAGE, TNF-α and TGF-β genes was significantly higher in the diabetes group compared to the healthy group. The expression of these genes decreased in groups treated with crocin and Losartan compared to the diabetes group. The highest reduction in RAGE and TGF-β gene expression was reported in those treated with crocin + Los. Histopathology results showed that the diabetes group had more bile ducts and necrosis than the healthy control group, which had no tissue changes. Hepatocyte degeneration, bile duct proliferation, inflammatory changes and hepatocyte necrosis were mild in the treated groups, but no hepatocyte necrosis was observed in the crocin + Los group. Crocin may be a feasible therapeutic agent for treating diabetes and its symptoms when combined with pharmaceutical medications. Human research is still needed to reach clear conclusions.