Lower Aspartate Aminotransferase Research Articles

Serum Transaminases And Older Adults: Distribution And Associations With All-Cause Mortality.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults is understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥ 70 years) and assess for associations with mortality. Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality. Of the 11853 participants with ALT and AST levels, 1054 (8.9%) deaths were recorded over median 6.4 (IQR 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 U/L and 5-13 U/L respectively; for AST, the lowest quintiles were 8-18 U/L and 7-17 U/L. On both univariate and models adjusted for covariates including age, BMI, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% CI 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88] respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers. Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only impacted older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered.

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node

AimsThe identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this...

Assessment of hemodynamic and blood parameters that may reflect macroscopic quality of porcine kidneys during normothermic machine perfusion using whole blood

PurposeUsing ex vivo normothermic machine perfusion (NMP) with whole blood we assessed marginal porcine kidneys under reperfusion. The aim was to link measureable machine and clinical blood parameters with the currently used visual assessment. This could serve as a baseline for a standardized evaluation score to identify potentially transplantable kidneys in the future.MethodsKidneys and autologous whole blood were procured from slaughterhouse pigs (n = 33) and were perfused for 4 h using NMP. The hemodynamic parameters arterial pressure (AP), renal blood flow (RBF) and intrarenal resistance (IRR) were measured. Activity of aspartate transaminase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and lactate were assessed in blood at 0/1/2/4 h. Kidneys were grouped into “potentially transplantable” (PT) or “not transplantable” (NT) based on their overall macroscopic appearance after NMP by an experienced physician.ResultsPT-kidneys (n = 20) had a significantly lower IRR and higher RBF than NT-kidneys (n = 13). GGT, ALP and LDH did not differ significantly, but at 4 h, AST was significantly higher in PT-kidneys compared to NT-kidneys. Lactate levels kept increasing during NMP in NT-kidneys and were significantly higher at 1/2/4 h than in PT-kidneys.ConclusionThe immediately assessed macroscopic aspects of examined kidneys correlated with hemodynamic parameters, increased lactate and lower AST in this study. In the future, NMP with whole blood could be a useful tool to extend the donor pool by allowing the assessment of otherwise unknown characteristics of marginal kidneys before transplantation.

Cross-sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases.

Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data. The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P<0.001). The FGF19 levels in participants with obese were lower than those without obese (P<0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P<0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P<0.05). Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.

Preventing High Fat Diet-Induced Obesity and Related Hepatic Steatosis by Chlorin e6-Mediated Photodynamic Therapy.

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.

Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study.

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inversevariance weightedmethodanalysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, β = -1.372, p = 0.045), and basophil counts (Baso, β = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

Exploring the effects of ursodeoxycholic acid-probiotic combination on Lactobacillus and liver enzyme levels for cholestasis management: An experimental study

Background: Cholestasis arises from compromised bile secretion due to hepatocyte dysfunction, leading to liver impairment. Available treatments show limited efficacy, with ursodeoxycholic acid (UDCA) being a primary option. Cholestatic conditions influence gut microbiota; therefore, probiotic therapy emerges as a potential approach. Objective: This investigation aimed to evaluate the impact of combined administration of probiotics and UDCA on Lactobacillus levels, as well as the levels of the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats with restricted common bile ducts .Methods: A total of 35 male Sprague Dawley rats were randomly assigned to 7 groups, each comprising 5 members: K1 (healthy control), K2 (negative control with cholestasis), K3 (positive control with cholestasis given UDCA), K4 (cholestasis given 36 mg probiotics), K5 (cholestasis given 18 mg probiotics and UDCA), K6 (cholestasis given 36 mg probiotics and UDCA), and K7 (cholestasis given 54 mg probiotics and UDCA). The treatment duration was 21 days, during which blood samples were collected for AST and ALT analysis. Lactobacillus count was determined by quantitative polymerase chain reaction (PCR) analysis of fecal samples.Results: When UDCA and probiotics were given together in three different dosages, the Lactobacillus count significantly increased (p&lt;0.05) compared to the other groups. Furthermore, compared to the other treatment groups, the UDCA-probiotic combination group exhibited noticeably lower AST and ALT values.Conclusion: Combining UDCA and probiotics elevated Lactobacillus count and decreased AST and ALT levels in cases of cholestasis more effectively than single therapy.

Serum aspartate aminotransferase, a novel potential biomarker of prognosis in extranodal natural killer/T cell lymphoma, nasal type.

Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups' overall survival (OS) and progression-free survival (PFS). Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. AST might represent a significant prognostic marker for ENKTL patients.

Association of whole blood copper, zinc, calcium, magnesium, and iron with non-alcoholic fatty liver disease in overweight and obese children.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group (n=400) and a NAFLD group (n=202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH. A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m2. The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P<0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH. High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL/6J Mice.

Human milk is naturally rich in medium- and long-chain triacylglycerols (MLCT), accounting for approximately 30% of the total fat. However, infant formula fat is prepared using a physical blend of vegetable oils, which rarely contains MLCT, similar to human milk. The differences in MLCT between human milk and infant formulas may cause different lipid metabolisms and physiological effects on infants, which are unknown. This study aimed to analyze the metabolic characteristics of formula lipid containing novel human milk fat substitutes based on MLCT (FL-MLCT) and compare their effects with those of the physical blend of vegetable oils (FL-PB) on lipid metabolism and gut microbiota in mice. Compared with the FL-PB group, the FL-MLCT group showed increased energy expenditure, decreased serum triacylglycerol level, and significantly lower aspartate aminotransferase level, epididymal and perirenal fat weight, and adipocyte size. Moreover, the abundances of Firmicutes/Bacteroidota, Actinobacteriota, and Desulfovibrionaceae were significantly decreased in the FL-MLCT group. Novel human milk fat substitutes MLCT could inhibit visceral fat accumulation, improve liver function, and modulate the mice gut microbiota composition, which may contribute to controlling obesity.

Effect of pre and postpartum maternal supplementation of zinc and selenium via slow-release glass bolus or the element salts on feed intake and some blood parameters in ewes and their lambs

In late pregnancy and early lactation, ewe's demand increases for zinc (Zn), and selenium (Se) for scavenging of free radicals and due to transfer via placenta, colostrum or milk to lamb.This experiment was conducted to study the effect of slow-release bolus of Zn and Se on performance, and some blood parameters of pregnant ewes in the last third of pregnancy, and early lactation as well as their lambs. Twenty-one ewes were estrus synchronized in the breeding season by intra vaginal insertion of sponge containing medroxyprogesterone acetate. Forty-five days before the expected date of parturition, the pregnant ewes (3–4 years old and 55±5.2 kg in weight) were randomly assigned to one of the three groups: 1) control, 2) slow-release glass bolus with mean release of 20 mg Zn and 0.2 mg Se per day (Bolus), and 3) 20 mg Zn and 0.2 mg Se per day as sulfate and selenite, respectively via Daily feeding (Daily). Blood samples were obtained from ewes at 105th and 135th days of pregnancy, at parturition and 15th day postpartum and from lambs at 15 days of age. The results indicated that total feed intake of ewes increased (P = 0.03) in the Bolus and Daily groups than control. Supplementation of Zn and Se in both methodssignificantly increased Total Antioxidant Capacity (TAC) in the ewesand their lambs than the control group. Compared with the control, there was higher triiodothyronine (T3) in ewes and their lambs and lower tetraiodothyronine (T4) only in lambs in Bolus and Dailygroups. Increased T3 to T4 ratio in ewes (at days 135 of pregnancy and at parturition) and their lambs was recorded in Bolus and Daily than the control group. An increased level of alkalinephosphatase (ALP) in ewes was observed in the Bolus and Daily groups compared with the control. Alanine amino transferase (ALT) activity on day 135 of pregnancy was significantly reduced by Zn and Se supplementation in both methods. Bolus and Daily groups of ewes had lower creatinephosphokinase (CPK), and their lambs had lower aspartate amino transferase (AST), ALT, CPK, and gamma-glutamyltransferase (GGT) than the control group. Regardless of the supplementation method, Zn and Se increased glucose (P = 0.02) and decreased triglyceride (P = 0.06) in ewes. In the ewes supplemented with Zn and Se, creatinine concentration significantly decreased in parturition day compared to control. Total protein, albumin, globulin and ratio of albumin to globulin in ewes and their lambs were not different between treatments. As a result, Zn and Se improved antioxidant status and some blood parameters in ewes and their lambs. Efficacy of slow-release bolus of Zn and Se was similar with daily feeding of these elements.

Modulatory effects of dietary prickly pear (Opuntia ficus-indica) peel on high salinity tolerance, growth rate, immunity and antioxidant capacity of Nile tilapia (Oreochromis niloticus)

This study evaluated the effects of prickly pear (Opuntia ficus-indica) peel (PPP) on salinity tolerance, growth, feed utilization, digestive enzymes, antioxidant capacity, and immunity of Nile tilapia (Oreochromis niloticus). PPP was incorporated into four iso-nitrogenous (280 g kg−1 protein) and iso-energetic (18.62 MJ kg−1) diets at 0 (PPP0), 1 (PPP1), 2 (PPP2), and 4 (PPP4) g kg−1. Fish (9.69 ± 0.2 g) (mean ± SD) were fed the diets for 75 days. Following the feeding experiment, fish were exposed to a salinity challenge (25‰) for 24 h. Fish survival was not affected by the dietary PPP inclusion either before or after the salinity challenge. Fish fed the PPP-supplemented diets showed lower aspartate aminotransferase, alanine aminotransferase, cortisol, and glucose levels compared to PPP0, with the lowest values being observed in PPP1. Fish fed dietary PPP had higher growth rates and feed utilization than PPP0. Quadratic regression analysis revealed that the best weight gain was obtained at 2.13 g PPP kg−1 diet. The highest activities of protease and lipase enzymes were recorded in PPP1, while the best value of amylase was recorded in PPP2, and all PPP values were higher than PPP0. Similarly, PPP1 showed higher activities of lysozyme, alternative complement, phagocytic cells, respiratory burst, superoxide dismutase, glutathione peroxidase and catalase, and lower activity of malondialdehyde than in PPP0. Further increases in PPP levels above 2 g kg−1 diet led to significant retardation in the immune and antioxidant parameters. Thus, the inclusion of PPP at about 1 to or 2 g kg−1 diet can improve stress tolerance, immunity, and antioxidant capacity in Nile tilapia.

Gestational exposure to the great Chinese famine: early life undernutrition impact on prostatic hyperplasia in adulthood.

Benign prostatic hyperplasia (BPH) is a frequent illness in aged men that impacts their quality of life; early childhood exposure to famines may have long-term effects on the chance of developing BPH. The aim of this study is to investigate the relationship between early-life famine exposure and benign prostatic hyperplasia (BPH) risk in Chinese men born during 1959-1961. We used medical records from a large, comprehensive hospital to screen people born in China during the years of famine (1959-1961). Birthplaces were identified as indicators of famine exposure status. In the time window between 2017 and 2022, people born during the famine years who had prostatic ultrasonic examinations were selected, and their medical records were retrieved from the database. Univariate and multivariate logistic regression analyses investigated the relationship between famine exposure and BPH risk. A total of 3,009 subjects were included in this study. Patients with heavy famine exposure had older age, shorter height, lighter weight, lower cholesterol, lower uric acid (UA), lower aspartate aminotransferase (ALT), and a higher incidence of BPH than those with light famine exposure (all p < 0.05). Univariate logistic regression showed that BPH was positively related to famine exposure, age, height, weight, and body mass index (BMI) but negatively related to UA (all p < 0.05). Multivariate logistic regression showed that age and famine exposure were still independent risk factors (p < 0.05), while UA was an independent protective factor for BPH (p < 0.05). Heavy famine exposure increased the risk of BPH (adjusted OR = 1.214, 95% CI = 1.05-1.467, p = 0.045). Famine and malnutrition exposure during early life may be independent risk factors for BPH in Chinese adults. This relationship provides additional evidence to support the fetal origins of adult diseases and offers clues for the pathological mechanisms of BPH.

Dexmedetomidine's Effects on the Livers and Kidneys of Rats with Pancreatic Ischemia-Reperfusion Injury.

Pancreatic surgeries inherently cause ischemia-reperfusion (IR) injury, affecting not only the pancreas but also distant organs. This study was conducted to explore the potential use of dexmedetomidine, a sedative with antiapoptotic, anti-inflammatory, and antioxidant properties, in mitigating the impacts of pancreatic IR on kidney and liver tissues. A total of 24 rats were randomly divided into four groups: control (C), dexmedetomidine (D), ischemia reperfusion (IR), and dexmedetomidine ischemia reperfusion (D-IR). Pancreatic ischemia was induced in the IR and D-IR groups. Dexmedetomidine was administered intraperitoneally to the D and D-IR groups. Liver and kidney tissue samples were subjected to microscopic examinations after hematoxylin and eosin staining. The levels of thiobarbituric acid reactive substances (TBARS), aryllesterase (AES), catalase (CAT), and glutathione S-transferase (GST) enzyme activity were assessed in liver and kidney tissues. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine were measured. A comparison of the groups revealed that the IR group exhibited significantly elevated TBARS (p<0.0001), AES (p=0.004), and CAT enzyme activity (p<0.0001) levels in the liver and kidney compared to groups C and D. Group D-IR demonstrated notably reduced histopathological damage (p<0.05) and low TBARS (p<0.0001), AES (p=0.004), and CAT enzyme activity (p<0.0001) in the liver and kidney as well as low AST and ALT activity levels (p<0.0001) in the serum compared to the IR group. The preemptive administration of dexmedetomidine before pancreatic IR provides significant protection to kidney and liver tissues, as evidenced by the histopathological and biochemical parameters in this study. The findings underscored the potential therapeutic role of dexmedetomidine in mitigating the multiorgan damage associated with pancreatic surgeries.

Immunosuppression minimization is safe and associated with good long-term success in pediatric recipients of liver transplant.

Immunosuppression reduction after liver transplant is an important strategy to mitigate long-term medication side effects. We describe our center's experience with immunosuppression minimization to once-daily calcineurin inhibitor dosing. Success was defined as continuing daily calcineurin inhibitor monotherapy with normal transaminases and no rejection. We performed a retrospective review of eligible children who received a liver transplant between 2009 and 2016, had a surveillance biopsy, and were on twice-daily calcineurin inhibitor monotherapy. Twenty-eight of 51 eligible patients were minimized to daily calcineurin inhibitor with goal 12-hour trough detectable. Nineteen patients (68%) had 1-year success, and 17 (61%) had long-term success at a median follow-up of 5.0 years (interquartile range (IQR): 2.9-6.6). Minimization failure occurred at a median of 0.6 years (IQR: 0.3-1.0) after dose reduction. Patients with long-term success had lower aspartate aminotransferase levels prior to minimization compared to those who failed with a median of 28.0IU/L (IQR: 20.5-32.0) versus 32.0IU/L (IQR: 30.0-37.0), p = 0.047. The long-term success group demonstrated a trend toward greater recipients of liver transplant from living donors (53% vs. 18%, p = 0.07). At the time of the last follow-up at a median of 5.0 years (IQR: 2.9-6.1) after surveillance biopsy, most (73%) patients who failed had returned to twice-daily calcineurin inhibitor monotherapy, all had liver enzymes <2 times the upper limit of normal, and there were no patient deaths or graft losses. In conclusion, immunosuppression minimization is safe in pediatric recipients of liver transplant and should be considered to reduce long-term medication side effects and improve patient quality of life. Future studies are necessary to follow long-term outcomes and develop biomarkers to predict minimization success.

Machine perfusion preservation with hemoglobin based oxygen vesicles alleviate ultrastructural damages in porcine liver donated after cardiac death.

Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor grafts. It was reported that oxygenation during MMP reduces portal venous resistance and increases bile production. The MMP with hemoglobin-based oxygen vesicles (HbV) keeps the lower aspartate aminotransferase level (an indicator of liver injury) and maintains the functional ultrastructure of mitochondria in the hepatocytes. To evaluated differences of ultrastructural damages in donor livers between the MMP with and without HbV, porcine liver grafts after 60 min of warm ischemia were perfused at 22°C for 4 h with or without HbV, and a part of liver grafts were analyzed by transmission electron microscopy (TEM) and osmium-maceration scanning electron microscopy (OM-SEM). The remaining grafts were perfused with autologous blood at 38°C for 2 h in an isolated liver reperfusion model (IRM) that mimics the inside of the body after transplantation, and then analyzed by TEM and OM-SEM. Hepatocytes after MMP had small round mitochondria with rod-shaped cristae and reticulovesicular rough endoplasmic reticulum (rER) in both HbV(+) and HbV(-) livers. After IRM of HbV(+) livers, the well-developed lamellar rER was often found in hepatocytes. Liver sinusoidal endothelial cells (LSECs) after MMP contained some large vacuolar structures containing amorphous garbage in the cytoplasm, and their size along with appearance frequency were smaller and lower, respectively, in HbV(+) livers than HbV(-). Oxygenation during the MMP by using HbV suppressed the ultrastructural damages in donor livers, in particular for the LSECs. RESEARCH HIGHLIGHTS: Liver sinusoidal endothelial cells after midthermic machine perfusion had large vacuolar organelles with amorphous garbage. Oxygenation during the perfusion made them less and smaller, ultrastructurally supporting its utility.

Effect of replacing a portion of inorganic chloride trace minerals with trace mineral amino acid complexes

The objective was to determine whether replacing a portion of inorganic chloride trace minerals and cobalt carbonate in the diet with AA complexes of trace minerals and cobalt glucoheptonate will improve lactating cow performance, feed efficiency, and calf performance. In a clinical trial, 69 Holstein cows entering second lactation and greater were randomly assigned to 1 of 2 treatments, with the total dietary trace mineral concentration the same between treatments, starting 1 wk after dry off (50 to 57 d before expected parturition) until 154 d in milk (DIM): (1) an inorganic chloride trace mineral (ITM) blend consisting of Zn (75 mg/kg), Mn (65 mg/kg), and Cu (10 mg/kg) as hydroxychlorides and Co (1 mg/kg) as carbonate (n = 37) or (2) partial replacement of ITM with AA complexes of Zn (40 mg/kg), Mn (20 mg/kg), and Cu (3.5 mg/kg) and Co glucoheptonate (1 mg/kg; AATM; Availa-Dairy, Zinpro Corp.; n = 32). Dry matter intake (DMI) was recorded daily from enrollment through wk 8, and milk yields were recorded daily from calving through wk 22. Milk composition and body weights (BW) were collected weekly. Serum samples were analyzed for albumin (Alb), cholesterol (Chol), total bilirubin (Bili), aspartate aminotransferase (AST), haptoglobin, β-hydroxybutyrate (BHB), and Ca. A liver health index (LHI) was calculated based on Bili, Chol, and Alb concentrations. A liver functionality index (LFI) was calculated to standardize changes in Alb, Chol, and Bili from 4 to 29 DIM. Greater LHI and LFI indicate better health status. Colostrum was analyzed for IgG and Brix, and calf serum was analyzed for IgG. Calf growth was monitored through 9 wk of age (AATM: n = 12, ITM: n = 10). Data were analyzed using SAS software with mixed effects models and repeated-measures analysis, when applicable. Survival analysis for pregnancy by 154 DIM was analyzed by Cox proportional and Kaplan-Meier hazards models. Disorder incidence was tested with Fisher's exact test. Prepartum DMI as a percent of BW was lower in cows fed AATM and not significant postpartum. Cows fed AATM produced more milk from wk 1 to 8 and from wk 1 to 22. Energy-corrected milk yield and colostrum measures did not significantly differ between treatments. A treatment by time interaction was seen for AST and BHB; cows fed AATM tended to have lower AST concentrations at 28 DIM and lower concentrations in BHB through 29 DIM, though not statistically significant. Cows fed AATM had greater LHI at 4 DIM. Haptoglobin, Ca, LFI, hazard of pregnancy, risk to first service, survival curves, or services per pregnancy did not significantly differ. Calf serum IgG and birth weight did not significantly differ between treatments. Calves from dams fed AATM had greater average daily gain than calves from dams fed ITM. Overall, cows fed AATM during the dry period and early lactation had improved postpartum performance and potential health improvements.

Melatonin and metformin co-loaded nanoliposomes efficiently attenuate liver damage induced by bile duct ligation in rats.

In the current study, the therapeutic effectiveness of the metformin (Met) and melatonin (Mel) co-loaded liposomes was investigated on cholestasis induced by bile duct ligation (BDL) in male rats. Histopathological analysis, biochemical analysis, and oxidative stress markers were assayed to determine the therapeutic effect of Met and Mel co-loaded liposomes on cholestasis. Histopathological analysis revealed that the simultaneous administration of Met and Mel, whether in the free (C-Mel-Met) or liposomal (C-Lipo-Mel-Met) forms, reduced inflammation as well as proliferation of bile ducts; however, results were more prominent in the liposomal form of Mel and Met. Additionaly, serum levels of aspartate aminotransferase (AST) were significantly (p < 0.001) higher in (C-Mel-Met) treated rats compared with (BDL) rats; however, (C-Lipo-Mel-Met) treated rats exhibited significant (p < 0.05) lower AST rates in comparison to (BDL) rats. Moreover, a significant (p < 0.0001) drop in bilirubin levels was detected in (C-Lipo-Mel-Met) treated rats in comparison to (BDL) rats; it is noteworthy mentioning that bilirubin levels in (C-Lipo-Mel-Met) treated rats were insignificant in comparison to sham-control (SC) rats. Furthermore, rats concomitantly administered Met and Mel, exhibited significant downregulation in the expression levels of inflammatory cytokine genes such as TNF-α and IL-1 gene expression, where the downregulation was more prominent in the liposomal from. Our findings demonestrate that the concomitant administration of metformin and melatonin in the liposomal form had more therapeutic effect on liver injury than their free forms through improving histological changes, reducing biochemical markers and favoring oxidant- antioxidant balance.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity. In practical application, the research of food combinations is more significant than a specific food component. This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid (OA). Five indexes, triglyceride (TG), total cholesterol (T-CHO), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were used to evaluate the lipid-lowering effect of highland barley extract. We also preliminary studied the lipid-lowering mechanism by Real-time fluorescent quantitative polymerase chain reaction (qPCR). The results indicated that highland barley extract contains many components with lipid-lowering effects, such as hyperoside and scoparone. In vitro, the lipase assay showed an 18.4 % lipase inhibition rate when the additive contents of highland barley extract were 100 µg/mL. The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mM OA-induced HepG2 cells. The results showed that intracellular TG, LDL-C, and T-CHO content decreased by 34.4 %, 51.2 %, and 18.4 %, respectively. ALT and AST decreased by 51.6 % and 20.7 % compared with the untreated hyperlipidemic HepG2 cells. qPCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγ and Fabp4.

The Association between Liver Enzymes and Mortality Stratified by Non-Alcoholic Fatty Liver Disease: An Analysis of NHANES III

Associations between liver enzymes or De Ritis ratio (DRR; aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) and mortality stratified by non-alcoholic fatty liver disease (NAFLD), which have rarely been analyzed in previous studies, were investigated using the National Health and Nutrition Examination Survey (NHANES) III (1988–1994). Participants without risk factors for liver diseases other than NAFLD were linked with National Death Index records through 2019 (n = 11,385) and divided into two cohorts with or without NAFLD, based on ultrasound examination. Liver enzyme concentrations were categorized into sex-specific deciles and subsequently grouped (AST and ALT: 1–3, 4–9, 10; gamma glutamyltransferase (GGT): 1–8, 9–10). DRR was categorized into tertiles. Cox proportional hazards regression models adjusted for confounders were fitted to estimate associations with mortality. Compared with low levels, high GGT and DRR in participants with and without NAFLD had significantly higher hazard ratios for all-cause mortality. Compared with intermediate concentrations, low ALT showed higher all-cause mortality in participants with and without NAFLD, whereas low AST had higher HR in participants without NAFLD and high AST in those with NAFLD. Mortality was associated with liver enzymes or DRR in participants both with and without NAFLD, indicating that the relationship is not mediated solely by hepatocellular damage.