Liver Function Markers Research Articles

Acetaminophen-induced Liver Injury: Protective Effect of <i>Laportea aestuans</i> Aqueous Leaf Extract in Experimental Mice Model

Acetaminophen commonly referred to as paracetamol is an analgesic and antipyretic drug commonly available as over the counter medications. Indiscriminate use of acetaminophen for management of pain and fever causes liver damage. The study evaluated the hepatoprotective effect of the Laportea aestuans aqueous leaf extract in acetaminophen-treated mice. Group 1: control, Group 2: APAP treated, Group 3, 4, 5, 6 and 7 received 25, 50, 100, 200 and 400 mg/kg bw of the extract for 7 days and then treated with 300 mg/kg bw APAP respectively, Group 8: silymarin group. Biochemical parameters were analyzed. Activities of liver function marker enzymes (gamma- glutamyl transferase, alkaline phosphatase, lactate and glutamate dehydrogenases, aspartate, and alanine aminotransferases) were significantly (p< 0.05) lower in the serum of acetaminophen-treated mice pre-administered with the Laportea aestuans aqueous leaf extract extract when compared to the acetaminophen-treated control mice. Activities of antioxidant enzymes significantly (p<0.05) increased in groups pre-administered with the extract or silymarin. Histological micrographs also showed that the hepatic architectures of the preadministered mice were maintained following treatment with APAP. Pre-administration of 100 mg/kg bw of Laportea aestuans aqueous leaf extract gave the best protective effect against APAP-induced hepatotoxicity. Findings from this study showed that L. aestuans leaf extract evidently protects mice against acetaminophen-induced liver injury, exhibiting antioxidant and hepatoprotective properties. This study supports the ethnobotanical use of L. aestuans for the prevention and treatment of liver diseases.

A review of liver fibrosis and cirrhosis regression.

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

Independent and combined associations of urinary metals exposure with markers of liver injury: Results from the NHANES 2013–2016

BackgroundHeavy metals entering the human body could cause damage to a variety of organs. However, the combined harmful effects of exposure to various metals on liver function are not well understood. The purpose of the study was to investigate the independent and joint relationships between heavy metal exposure and liver function in adults. MethodsThe study involved 3589 adults from the National Health and Nutrition Examination Survey. Concentrations of urinary metals, including arsenic (As), cadmium (Cd), lead (Pb), antimony (Sb), barium (Ba), thallium (Tl), tungsten (W), uranium (U), were determined in urine using inductively coupled plasma mass spectrometry. Data for liver function biomarkers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transaminase (GGT), and alkaline phosphatase (ALP). Survey-weighted linear regression and quantile g-computation (qgcomp) were employed to evaluate the relationship of urinary metals with the markers of liver injury. ResultsCd, U and Ba were found to have positive correlations with ALT, AST, GGT, and ALP in the survey-weighted linear regression analyses. According to the qgcomp analyses, the total metal mixture was positively correlated with ALT (percent change: 8.15; 95% CI: 3.84, 12.64), AST (percent change: 5.55; 95% CI: 2.39, 8.82), GGT (percent change: 14.30; 95% CI: 7.81, 21.18), and ALP (percent change: 5.59; 95% CI: 2.65, 8.62), and Cd, U, and Ba were the main contributors to the combined effects. Positive joint effects were observed between Cd and U on ALT, AST, GGT and ALP, and U and Ba had positive joint effects on ALT, AST and GGT. ConclusionExposures to Cd, U, and Ba were individually associated with multiple markers of liver injury. Mixed metal exposure might be adversely correlated with markers of liver function. The findings indicated the potential harmful effect of metal exposure on liver function.

Protective Effects of White Kidney Bean (Phaseolus vulgaris L.) against Diet-Induced Hepatic Steatosis in Mice Are Linked to Modification of Gut Microbiota and Its Metabolites.

Disturbances in the gut microbiota and its derived metabolites are closely related to the occurrence and development of hepatic steatosis. The white kidney bean (WKB), as an excellent source of protein, dietary fiber, and phytochemicals, has recently received widespread attention and might exhibit beneficial effects on a high-fat diet (HFD)-induced hepatic steatosis via targeting gut microbiota and its metabolites. The results indicated that HFD, when supplemented with WKB for 12 weeks, could potently reduce obesity symptoms, serum lipid profiles, and glucose, as well as improve the insulin resistance and liver function markers in mice, thereby alleviating hepatic steatosis. An integrated fecal microbiome and metabolomics analysis further demonstrated that WKB was able to normalize HFD-induced gut dysbiosis in mice, thereby mediating the alterations of a wide range of metabolites. Particularly, WKB remarkably increased the relative abundance of probiotics (Akkermansiaceae, Bifidobacteriaceae, and norank_f_Muribaculaceae) and inhibited the growth of hazardous bacteria (Mucispirillum, Enterorhabdus, and Dubosiella) in diet-induced hepatic steatosis mice. Moreover, the significant differential metabolites altered by WKB were annotated in lipid metabolism, which could ameliorate hepatic steatosis via regulating glycerophospholipid metabolism. This study elucidated the role of WKB from the perspective of microbiome and metabolomics in preventing nonalcoholic fatty liver disease, which provides new insights for its application in functional foods.

Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis

To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis. Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups. During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05). The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.

Evaluation of Hepatoprotective Efficacy of a Polyherbal Unani Formulation Majoon-Najah against Cadmium Chloride-induced Liver Damage.

Majoon-Najah is a composite Unani formulation that consists of multiple medicinal plants and is advised for neurological illnesses. Several studies were carried out on Majoon-Najah (MN) and its ingredients to evaluate the protective effect against seizure and antidepressant activity in animals using a classical form as well as extract. Terminalia bellerica and Emblica officinalis are the major constituents of MN. Scientifically documented literature summarises the hepatoprotective potential of these constituents. The current study aimed to evaluate the possible hepatoprotective, antioxidant and antiinflammatory perspective of traditional Indian Unani formulation MN and Majoon-Najah hydroalcoholic extract (MNHE) in a Guinea pig model. Thirty adult male albino guinea pigs were randomly assigned into five groups for this study. MN and MNHE were given intragastrically for 15 days, followed by intraperitoneal Cadmium chloride (CdCl2, 3 mg/kg/day) from days 8 to 15, as per the schedule. Blood samples were taken from the heart on the 16th day, and the liver was operated on for biochemical analysis and histopathology under complete anesthesia. CdCl2 changed the levels of liver function markers, serum biochemical indicators like albumin, total protein, glucose, and cholesterol in the blood; lipid peroxidation (MDA), glutathione reductase (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in hepatic tissue homogenate, pro-inflammatory cytokines level and liver cytoarchitecture. MN and MNHE were found to protect guinea pigs' liver from CdCl2-induced injury by lowering raised parameters and increasing enzymatic antioxidants. MN and MNHE did not significantly heal injured liver tissues caused by CdCl2 in histopathological examinations. CdCl2 induces hepatotoxicity that is likely to worsen with increasing dosage and duration of exposure. MN and MNHE exert their hepatoprotective action by scavenging free radicals, decreasing malondialdehyde levels, activating antioxidant enzymes, and down-regulating proinflammatory indicators.

Liver Protective Effect of the Co-treatment of Rhei Radix et Rhizoma and Silymarin on TAA-induced Liver Injury

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model.Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining.Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22&lt;sup&gt;phox&lt;/sup&gt;, and p47&lt;sup&gt;phox&lt;/sup&gt;, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation.Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

Effects of 8 weeks of resistance training in combination with a high protein diet on body composition, muscular performance, and markers of liver and kidney function in untrained older ex-military men.

The effects of a high protein diet in combination with chronic resistance training (RT) on skeletal muscle adaptation responses in untrained older ex-military men is unknown. Therefore, we compared the effects of 8 weeks of RT in combination with either a high (1.6 g/kg/d) or low protein diet (0.8 g/kg/d) on body composition [skeletal muscle mass (SMM) and body fat percentage (BFP)], muscular strength, power, and endurance (upper and lower body), markers of liver [alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] and kidney (creatinine and urea) function, and lipid profile low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cholesterol levels in a cohort of healthy, untrained older ex-military males. Forty healthy untrained older ex-military males (age: 61 ± 2 yr, body mass index: 23.2 ± 1.3 kg.m-2) performed 8 weeks (three sessions·w-1) of RT with either 1.6 g/kg/d (RHP; n = 20) or 0.8 g/kg/d of protein (RLP; n = 20). Body composition (assessed by Inbody 720), muscular strength (1-RM for chest and leg press), power (Wingate test), endurance (75% 1-RM for chest and leg press), and markers of liver and kidney function (biochemical kits) were assessed pre and post-intervention. SMM and muscular strength (upper and lower body) increased post-intervention in both groups and were significantly greater in RHP compared to RLP, while muscular power increased to the same extent in both groups (p < 0.05) with no between-group differences (p > 0.05). In contrast, there were no post-intervention changes in muscular endurance, HDL, and BFP remained in either group (p > 0.05). ALT and creatinine significantly increased in RHP compared to RLP while GGT, AST, and urea only increased in the RLP group (p < 0.05). LDL and cholesterol significantly decreased in both groups (p < 0.05). A daily intake of 1.6 g/kg/d protein was superior to 0.8 g/kg/d (current recommended daily intake) for promoting greater improvements in SMM and muscle strength and thus may be a more suitable level of intake for promoting such adaptive responses. Notwithstanding observed between-group differences in ALT and creatinine and the fact that levels remained within normal ranges, it is feasible to conclude that this daily protein intake is efficacious and well tolerated by healthy, untrained older ex-military males.

The Effects of Lead on Some Markers of Liver and Kidney Functions of Lead Recycling Factory Workers are Mediated Through Increased Oxidative Stress

The Effects of Lead on Some Markers of Liver and Kidney Functions of Lead Recycling Factory Workers are Mediated Through Increased Oxidative Stress

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

A review of liver fibrosis and cirrhosis regression

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives.

This study demonstrates high drug-loading of novel pyridine derivatives (S1-S4) in lipid- and polymer-based core-shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core-shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.

Effect of Ramadan Fasting on DNA Repair, Immune System, Inflammation and Cognitive Function in Chronic Kidney Disease Patients: A Systematic Literature Review

Background: There have been many studies that say Ramadan fasting has a positive effect on reducing BMI, blood sugar, inflammatory factors, and DNA Repair. However, there are still no guidelines for fasting in patients with chronic kidney disease (CKD) both nationally and internationally. This study aimed to conduct a review to explore the effects of Ramadan fasting against chronic kidney disease, specifically on DNA repair, Immune System, Inflammation, and Cognitive Function in patients with chronic kidney disease.&#x0D; Methods: This study is a systematic literature review (SLR) with sources obtained from various reputable journal databases such as PubMed, Cochrane Library, EBSCO, and Elsevier using relevant keywords. The selected articles have passed the inclusion and exclusion criteria. A total of 39 articles that discuss fasting were obtained from Ramadan in chronic kidney disease patients on metabolic response and inflammatory markers in the body.&#x0D; Results: Ramadan fasting has a positive effect on the response to anti-inflammatory, expression of protective genes, markers of kidney and liver function, protective proteome, and oxidative stress.&#x0D; Conclusion: Ramadan fasting may provide a short-term protective effect against levels of systemic inflammation.

Alterations in Biochemical Markers of Liver and Kidney Function and Oxidative Stress Indices on Sub-acute Exposure of Meloxicam in Albino Rats

Background: The study was performed to study the alterations in biochemical markers of liver and kidney function and oxidative stress indices on sub-acute exposure of meloxicam in albino rats. Methods: The study was performed in three groups of rats, consisting six rats in each group. The rats of group I were served as control. However, rats of group II, III were treated with meloxicam @ 0.2 mg/kg b.wt. meloxicam @ 0.6 mg/kg b.wt. respectively. Result: Meloxicam administration induced oxidative stress in rats as indicated by significant decrease in concentration of catalase, superoxide dismutase and reduced glutathione in blood as compared to control. However, lipid peroxidation was significantly enhanced as indicated by increased level of MDA in blood as compared to control. Meloxicam altered the functions of liver and kidney as indicated by the alteration in the biochemical markers of liver and kidney function. Meloxicam significantly enhanced the concentration of biochemical markers of liver function viz. ALT, AST, GGT, ALP, albumin and bilirubin as compared to control. The concentration of biochemical markers of kidney function viz. BUN and creatinine was significantly enhanced after meloxicam administration as compared to control.

Extracellular Vesicles as Markers of Liver Function: Optimized Workflow for Biomarker Identification in Liver Disease.

Liver diseases represent a significant global health burden, necessitating the development of reliable biomarkers for early detection, prognosis, and therapeutic monitoring. Extracellular vesicles (EVs) have emerged as promising candidates for liver disease biomarkers due to their unique cargo composition, stability, and accessibility in various biological fluids. In this study, we present an optimized workflow for the identification of EVs-based biomarkers in liver disease, encompassing EVs isolation, characterization, cargo analysis, and biomarker validation. Here we show that the levels of microRNAs miR-10a, miR-21, miR-142-3p, miR-150, and miR-223 were different among EVs isolated from patients with nonalcoholic fatty liver disease and autoimmune hepatitis. In addition, IL2, IL8, and interferon-gamma were found to be increased in EVs isolated from patients with cholangiocarcinoma compared with healthy controls. By implementing this optimized workflow, researchers and clinicians can improve the identification and utilization of EVs-based biomarkers, ultimately enhancing liver disease diagnosis, prognosis, and personalized treatment strategies.

Sub-Acute Toxicity Profile of Aqueous Leaf Extract of Pavetta crassipes (K. Schum) in Rats

Pavetta crassipes is a plant with many ethnomedicinal uses but has limited published data on its safety. The aim of the study was to evaluate the subacute oral toxicity of aqueous leaf extract of P. crassipes in Wister rats. Thirty-six Wister male rats were randomly divided into 6 groups of six rats each. They were treated with; 1 mL/kg distilled water (negative control group), aqueous leaf extract of P. crassipes (125, 250 and 500 mg/kg test groups respectively), 10 mg/kg furosemide (positive control group 1), and 10 mg/kg lisinopril (positive control group 2) daily for 28 days. Weekly animal weight, food consumption, water intake, fecal/urine outputs, organ tobody weight ratio, hematological, biochemical and histological assessment of organs were used to evaluating toxicity. There was no significant difference between all the groups in body weight, food/water intake, fecal output, plasma sodium, potassium, chloride, calcium and biochemical markers of liver and kidney function (p›0.05). However, P. crassipes leaf extract significantly increases the urine excretion, high density lipoprotein (HDL) and endogenous antioxidant (p‹0.05) with a decrease in total cholesterol, triglyceride and low density lipoprotein (p‹0.05) in rats. Aqueous leaves extract of P. crassipes is relatively safe because the biochemical parameters and organs assayed were within the values for distilled water treated rats.&nbsp

Full-Right Full-Left Split Liver Transplantation for Two Adult Recipients: A Single-Center Experience in China.

The most effective treatment for end-stage liver diseases is liver transplantation, which is impeded by the shortage of donor livers. Split liver transplantation (SLT) is important for addressing the donor liver shortage. However, full-right full-left SLT for two adult recipients is globally rarely conducted. This study aimed to investigate the clinical outcomes of this technique. We retrospectively analyzed the clinical data of 22 recipients who underwent full-right full-left SLT at Shulan (Hangzhou) Hospital between January, 2021 and September, 2022. The graft-to-recipient weight ratio (GRWR), cold ischemia time, operation time, length of the anhepatic phase, intraoperative blood loss, and red blood cell transfusion amount were all analyzed. The differences in liver function recovery after transplantation were compared between the left and right hemiliver groups. The postoperative complications and prognosis of the recipients were also analyzed. The livers of 11 donors were transplanted into 22 adult recipients. The GRWR ranged from 1.16-1.65%, the cold ischemia time was 282.86 ± 134.87 min, the operation time was 371.32 ± 75.36 min, the anhepatic phase lasted 60.73 ± 19.00 min, the intraoperative blood loss was 759.09 ± 316.84 mL, and the red blood cell transfusion amount was 695.45 ± 393.67 mL. No significant difference in the levels of liver function markers, total bilirubin, aspartate aminotransferase, or alanine aminotransferase between left and right hemiliver groups at 1, 3, 5, 7, 14, and 28 d postoperatively was observed (both p > 0.05). One recipient developed bile leakage 10 d after transplantation, which improved with endoscopic retrograde cholangiopancreatography-guided nasobiliary drainage and stent placement. Another developed portal vein thrombosis 12 d after transplantation and underwent portal vein thrombectomy and stenting to restore portal vein blood flow. A color Doppler ultrasound performed 2 d after transplantation revealed hepatic artery thrombosis in one patient, and thrombolytic therapy was administered to restore hepatic artery blood flow. The liver function of other patients recovered quickly after transplantation. Full-right full-left SLT for two adult patients is an efficient way to increase the donor pool. It is safe and feasible with careful donor and recipient selection. Transplant hospitals with highly experienced surgeons in SLT are recommended to promote using full-right full-left SLT for two adult recipients.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type II receptor.

The transforming growth factor β (TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type II receptor (TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway. To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis. Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8 (CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect. We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine (DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson's trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver. DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

Schistosomicidal, hepatoprotective and antioxidant activities of the N-acetyl-L-cysteine and/or praziquantel in experimental acute mansonic schistosomiasis.

Schistosomiasis is a tropical parasitic disease, in which the major clinical manifestation includes hepatosplenomegaly, portal hypertension, and organs fibrosis. Clinically, treatment of schistosomiasis involves the use of praziquantel (PZQ) and supportive care, which does not improve the patient's outcome as liver injuries persist. Here, we report for the first time the effect of N-acetyl-L-cysteine (NAC) and/or praziquantel (PQZ) on S. mansoni, hepatic granuloma, serum markers for liver function and oxidative damage in acute schistosomiasis. Infected mice were divided into control, NAC, PZQ and NAC+PZQ groups and uninfected into control and NAC groups. After infection, NAC (200mg/kg/day) was administrated until the 60th day and PZQ (100mg/kg/day) from the 45th to the 49th day, both orally. On day 61, the mice were euthanized for serum markers for liver function. Worms were recovered, fragments of intestine employed to ascertain the oviposition pattern, and the liver was used for histopathological analysis, histomorphometry, egg and granuloma counting and oxidative stress marker assays. NAC reduced the burden of worms and eggs and increased the dead eggs in intestinal tissue. NAC+PZQ brought about reduction in granulomatous infiltration and NAC and/or PZQ reduced levels of ALT, AST, and alkaline phosphatase and increased albumin. NAC, PZQ or NAC+PZQ reduced levels of the superoxide anion, lipid peroxidation and protein carbonyl and increased sulfhydryl groups. The reduction in parasitological parameters, granulomatous inflammation and oxy-redox imbalance suggests NAC acts as a adjuvant in treatment of acute experimental schistosomiasis.

Hepatic steatosis evidenced by computed tomography in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction

BackgroundNon-alcoholic fatty liver disease (NAFLD) and acute myocardial infarction (AMI) have common pathological links. This study investigates the prognostic impact of NAFLD assessed as hepatic steatosis (HS) by computed tomography (CT) in AMI patients and explores the mechanistic role of NAFLD in cardiovascular (CV) events using coronary angioscopy (CAS). MethodsWe retrospectively examined 342 AMI patients who underwent CT followed by primary percutaneous coronary intervention (PCI) between January 2014 and December 2019. HS was defined as a hepatic to spleen attenuation ratio of <1.0 on CT scans. Major cardiac events (MCE) included cardiac death, non-fatal myocardial infarction, target-vessel revascularization, and target-lesion revascularization. ResultsHS was identified in 88 patients (26 %). Patients with HS were significantly younger, had a higher body mass index, and higher hemoglobin A1c, triglyceride, and malondialdehyde low-density lipoprotein levels (all p < 0.05). MCE occurred more frequently [27 (30.7 %) vs. 39 (15.4 %), p = 0.001] in the HS group than in the non-HS group. In the multivariate analysis, the presence of HS was an independent predictor of MCE after adjusting for metabolic risk factor and liver function markers. Among the 74 patients who underwent CAS for a median of 15 days after primary PCI, 51 (69 %) had intrastent thrombus, which was strongly associated with the presence of HS [18 (35 %) vs. 1 (4 %), p = 0.005]. ConclusionsAMI patients with NAFLD detected by CT often had CAS-derived intrastent thrombi and were at a high risk for CV events. Therefore, these patients should be carefully monitored.