Blood Alanine Aminotransferase Levels Research Articles

Multi-omics reveals that 5-O-methylvisammioside prevention acute liver injury in mice by regulating the TNF/MAPK/NF-κB/arachidonic acid pathway

BackgroundThe pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. PurposeIn the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. Methods & ResultsOur findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1β, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1β in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. ConclusionThe present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl4-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl4. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

Hepatoprotective and nephroprotective effects of Tessaria integrifolia Ruiz and Pav. on diclofenac-induced toxicity in rats.

Tessaria integrifolia Ruiz and Pav. (also known as "Pájaro bobo") is known for its medicinal properties, including antiulcer, antiasthmatic, leishmanicidal, antipyretic, antispasmodic, diuretic, anti-inflammatory, analgesic, and hepatoprotective effects. Therefore, we aimed to evaluate its hepatoprotective and nephroprotective effects using a rat model of diclofenac-induced toxicity. We administered three different doses of the methanolic extract of T. integrifolia (100, 200, and 400 mg/kg/day orally) and compared them with the commercial medicine silymarin (100 mg/kg orally). The rats received the T. integrifolia extracts for 5 days, and on days 3 and 4, 1 h after receiving the extracts, diclofenac was administered intraperitoneally at a dose of 50 mg/kg. The animals were euthanized 48 h after the last diclofenac injection, and blood samples were obtained to measure biochemical parameters related to liver and kidney function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, cholesterol, triglycerides, creatinine, and urea. Kidney and liver tissues were preserved in 10% formaldehyde and sent for histopathological analysis. The results show that T. integrifolia has hepatoprotective and nephroprotective effects. These effects are verified by the lower blood levels of ALT, AST, urea, and creatinine compared to the diclofenac group, which exhibited elevated biochemical parameters. In addition, histopathological analysis showed that the groups that received T. integrifolia did not display necrosis or infiltration, which were observed in the diclofenac group. The methanolic extract of T. integrifolia has hepatoprotective and nephroprotective effects, with the highest protective activity observed at a dose of 400 mg/kg/day.

Efficacy and safety of oral Nigella sativa oil for symptomatic treatment of knee osteoarthritis: A double-blind, randomized, placebo-controlled clinical trial

Background and purposeThe oil of Nigella sativa (NS) seeds has analgesic and anti-inflammatory effects. Therefore, the efficacy and safety of NS oil in the treatment of knee osteoarthritis were evaluated. Materials and methodsOne hundred and sixteen patients aged 50–70 years were randomly assigned to take 2.5 mL NS oil (N = 58) or placebo (N = 58) orally every 8 h for 1 month. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was the primary outcome measure and Visual Analog Scale (VAS) for pain, number of 500 mg acetaminophen tablets taken per day during the trial, patients’ satisfaction with the interventions, complete blood count and the blood levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine and blood urea nitrogen were the secondary outcome measures. ResultsFifty two and 54 patients respectively in the NS oil and placebo groups completed the study. The VAS scores were decreased by 33.96 ± 17.04% (NS oil group) and 9.21 ± 0.32% (placebo group) (p < 0.001), and WOMAC total scores were decreased by 27.72 ± 18.61% (NS oil group) and 1.34 ± 2.31% (placebo group) (p < 0.001) compared to baseline. The NS oil reduced the dose of acetaminophen significantly compared with the placebo (p = 0.001). The patients were significantly more satisfied with the NS oil than the placebo (p < 0.001). The NS oil had no significant effect on the other variables. There was no side effect. ConclusionOral NS oil safely reduces the osteoarthritis symptoms and analgesic dose in the knee osteoarthritis patients.

Assessment of the Health Status of Children Exposed to Industrial Toxicants in the Towns with Developed Non-Ferrous Metallurgy of the Sverdlovsk Region

Introduction: In the Sverdlovsk Region, the risks posed by cadmium, arsenic and lead exposures account for higher disease rates in the most sensitive groups of population. Recent studies have shown that these toxicants have an effect on mineral metabolism, damage to liver cells, kidneys, immunity indicators, and the nervous system. Objective: To assess the levels of cadmium, lead and arsenic in biological fluids of preschool children aged 3–6 years, living in towns with developed non-ferrous metallurgy, and possible changes in the health status at the detected level of toxicity. Materials and methods: The study was conducted in six towns of the Sverdlovsk Region with developed non-ferrous metallurgy. Environmental pollution in the study areas was assessed based on data of socio-hygienic monitoring. Biological monitoring was carried out to establish the levels of toxicants in blood and urine of children. A descriptive analysis of chronic morbidity in preschool children was performed, and the results of a special health examination of children (including that by a pediatrician and a neurologist) were presented. Mathematical modeling using decision trees was carried out. Results: Health monitoring data indicate an excess of the average regional prevalence rates in the studied preschoolers in nine disease categories. According to the results of an in-depth examination of the preschool children, diseases of the skin and subcutaneous tissue, diseases of the respiratory system, blood diseases and individual disorders involving the immune mechanism, and digestive diseases prevailed. Among concomitant diseases, the most prevalent were diseases of the digestive, nervous, and respiratory systems. Assessment of the neurological status showed that the largest percentage of children had residual cerebral insufficiency, attention deficit hyperactivity disorder, and cerebrastenic syndrome. Biomonitoring results indicated a higher level of lead, arsenic and cadmium in the biological fluids of those children. Mathematical modeling demonstrated statistically significant correlations between lead, cadmium, and arsenic concentrations in environmental objects, biomonitoring results, and clinical and laboratory examination data of children (the blood levels of alanine aminotransferase, zinc, total protein, phagocytic index, and the carrier of the marker of apoptosis CD95+). Conclusions: The results of biological monitoring were consistent with data on chronic morbidity in preschool children. Modeling data provided the body burden of toxicants, above which deviations of clinical and laboratory parameters from the reference values may occur. The findings can be used in implementation of targeted measures for disease prevention.

Dietary vitamin C in pre-parturient dairy cows and their calves: blood metabolites, copper, zinc, iron, and vitamin C concentrations, and calves growth performance.

The aim of this study was to evaluate the effects of dietary vitamin C supplementation on blood parameters of pre-parturient (PP) dairy cows and growth performance and immune system of their newborn calves. Forty PP cows (at approximately 21days before calving and an average weight 791 ± 50kg) were allocated into two experimental treatments: (1) basal diet without vitamin C supplementation (CO) and (2) basal diet with 20g of vitamin C supplementation from 21days before calving to parturition (VC). After parturition, the experiment continued by grouping the calves into four dietary treatments with 8 calves in each treatment. The experimental treatments were (1) control calves with no vitamin C supplementation and from cows that received no vitamin C supplement (CON), (2) calves supplemented with 600mg of vitamin C per day and from cows that received no vitamin C supplement (CVC), (3) calves supplemented with no vitamin C and from cows that received 20g of vitamin C per day (MVC), and (4) calves supplemented with 600mg of vitamin C per day and from cows that received 20g of vitamin C per day (CMVC). Serum concentrations of glucose, HDL and LDL, cholesterol, triglycerides, total protein, and albumin of cows were not affected by vitamin C supplementation during pre-parturient period. However, cows that received VC diet had lower (P < 0.05) malondialdehyde (MDA) and aspartate aminotransferase (AST) concentrations, higher total antioxidant capacity (TAC), and vitamin C concentration in their blood compared to CO cows. Vitamin C supplementation had no effect on plasma iron, copper, and zinc concentrations of PP cows. Similarly, vitamin C supplementation had no effect on total feed intake and feed conversion ratio (FCR) of suckling calves. However, calves in the CMVC group had higher (P < 0.05) overall daily weight gain compared to the other groups. Calves in the CVC and CMVC groups had lower (P < 0.05) blood MDA concentration on days 7 and 21. The highest (P < 0.05) blood TAC level was recorded in CMVC calves. Control group calves had lower (P < 0.05) blood superoxide dismutase activity compared to the other calves. Blood levels of alanine aminotransferase on days 7 and 21 and aspartate aminotransferase on day 7 were higher (P < 0.05) for calves in the CON and MVC groups. Based on the results, vitamin C supplementation had positive health effects on the oxidative parameters of PP dairy cows and also improved the performance and health status of the calves.

Resveratrol suppresses cholestasis-induced liver injury and fibrosis in rats associated with the inhibition of TGFβ1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers.

Cholestasis caused by slowing or blockage of bile flow is a serious liver disease that can lead to liver fibrosis and cirrhosis. The link between transforming growth factor beta 1 (TGFβ1), Smad family member 3 (Smad3), and microRNA 21 (miR21) in bile duct ligation (BDL)-induced liver fibrosis in the presence and absence of the anti-inflammatory and antioxidant compound, resveratrol (RSV), has not been previously studied. Therefore, we tested whether RSV can protect against BDL-induced liver fibrosis associated with the inhibition of the TGFβ1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers. The model group of rats had their bile duct ligated (BDL) for 3weeks before being killed, whereas, the BDL-treated rats were separated into three groups that received 10, 20, and 30mg/kg RSV daily until the end of the experiment. Using light microscopy and ultrasound examinations, we documented in the BDL group, the development of hepatic injury and fibrosis as demonstrated by hepatocytes necrosis, bile duct hyperplasia, collagen deposition, enlarged liver with increased echogenicity, irregular nodular border and dilated common bile duct, which were more effectively inhibited by the highest used RSV dosage. In addition, RSV significantly (p≤0.0027) inhibited BDL-induced hepatic TGFβ1, Smad3, miR21, the profibrogenic biomarker tissue inhibitor of metalloproteinases-1 (TIMP-1), malondialdehyde (MDA), interleukin-17a (IL-17a), and blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. These findings show that RSV at 30mg/kg substantially protects against BDL-induced liver injuries, which is associated with the inhibition of TGFβ1-Smad3-miR21 axis, and biomarkers of profibrogenesis, oxidative stress, and inflammation.

Latex proteins from Plumeria pudica reduce ligature-induced periodontitis in rats.

Previous studies have shown that latex proteins from Plumeria pudica (LPPp) have anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to evaluate the effects in rats of LPPp on ligature-induced periodontitis, an inflammatory disease. The animals were divided into groups: saline (animals without induction of periodontitis), periodontitis (induced periodontitis and untreated) and LPPp (induced periodontitis and treated with 40mg/kg). The following parameters were evaluated after 20 consecutive days of treatment: gingival bleeding index (GBI), probing pocket depth (PPD), alveolar bone height (ABH) and gingival myeloperoxidase (MPO) activity. In the hepatic tissue, malondialdehyde (MDA), glutathione (GSH) and histopathological alterations were evaluated. Blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Significant reduction in GBI, PPD and gingival MPO activity and ABH was seen in animals treated with LPPp compared with periodontitis. Values of GSH, MDA, ALT and histopathological evaluation were preserved in animals treated with LPPp. Treatment with LPPp improved clinical aspects of periodontitis, reduced the blood and hepatic alterations and prevented alveolar bone loss. Data suggest that LPPp have potential for treatment of periodontitis.

Lipid profile disturbances may predispose psoriatic patients to liver dysfunction.

IntroductionPsoriasis is a chronic inflammatory disease associated with metabolic disturbances and liver dysfunction. Both serum fatty acids (FA) and ceramides (Cer) have structural functions but also are signal molecules that could be involved in the pathogenesis of liver dysfunction.AimTo assess the concentration of the circulating FA and Cer in correlation with the alanine aminotransferase (ALT) blood level in psoriatic patients. In addition, we have examined the relationship between ALT concentration and severity of the disease and inflammation markers.Material and methodsEighty-five patients with psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 2 groups according to ALT blood levels. Serum concentration of 14 FA and 14 Cer were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile, and inflammatory markers.ResultsWe observed higher PASI score (p = 0.01) and higher C-reactive protein (p = 0.02) concentration in the group of psoriatic patients with high ALT. Serum ALT positively correlated with saturated fatty acids (SFA) (p = 0.01, r = 0.27) and SFA/unsaturated fatty acids (UFA) ratio (p = 0.01, r = 0.26). ALT negatively correlated with UFA level (p = 0.008, r = –0.28). Lignoceric ceramide positively correlated with ALT level (r = 0.22; p = 0.045) in psoriatic patients.ConclusionsPatients with severe psoriasis are predisposed to the development of liver dysfunction. We have demonstrated disturbances of serum fatty acid and sphingolipid profile in psoriatic patients, which may trigger liver disease.

Facile Synthesis and Nano-Silver Encapsulation of Paeonia emodi for Cardioprotective and Antihyperlipidemic Nursing Care Potentials

Paeonia emodi is a medicinal plant that is a vital family group of Paeoniaceae and traditionally utilized for treating cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, epilepsy, and palpitations. In this work, we have constructed P. emodi (Pemodi. EA) ethyl acetate subsegment of which was exposed to gain fractions via column chromatography. These subsegments were confirmed by various electroscopic methods. Further, the subsegments were examined for their cardioprotective property on induced isoproterenol hydrochloride (ISO) myocardial infractions (MIs) in nude mice. Pemodi-EA-40 was utilized with maximum segment for synthesis of silver nanoparticles (Pemodi.EA-40@AgNPs). The extreme active segments Pe-EA-40 were examined for antihyperlipidemic, cardioprotective, and histopathological examinations. The body weights of Pemodi.EA-40 (100 mg/kg) remarkably reduced the blood levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactic Acid Dehydrogenase (LDH), and Creatine Phosphokinase (CPK) associated with induced ISO treated groups. Pemodi.EA-40@AgNPs also reduced the ALT, AST, LDH, and CPK connected to the Pemodi.EA-40, respectively. The biochemical parameters and histological results reduced the changes as compared to induced ISO treated groups. The outcomes of our examinations proposed that the Pemodi.EA-40@AgNPs medicinal plant improves beneficial profiles of medicinal plant extract fragments for treatments and nursing care of myocardial infractions and atherosclerosis.

Effect of Entecavir on the Intestinal Microflora in Patients with Chronic HepatitisB: A Controlled Cross-Sectional and Longitudinal Real-World Study.

IntroductionThis study aimed to analyze the diversity of intestinal flora in patients with chronic hepatitis B (CHB) and investigate the effect of entecavir on the intestinal flora in these patients.MethodsThirty patients with CHB and 30 healthy controls were recruited from the Department of Infectious Diseases and Department of Gastroenterology of Shanghai Tongji Hospital between January 2017 and December 2018. Stool samples were collected for the detection of intestinal flora by high-throughput sequencing. Patients with CHB received antivirus therapy with entecavir for 8 weeks. The biochemical and virological responses were assessed and the intestinal flora were compared.ResultsAfter entecavir treatment, the blood levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF), and hepatitis B virus (HBV) DNA reduced significantly in patients with CHB and the species abundance of intestinal flora increased markedly. In patients with CHB, the unique genera included Butyrivibrio, Phaseolus acutifolius, and Prevotellaceae NK3B31 group before treatment and Howardella, Candidatus Stoquefichus, Citrobacter, Dysgonomonas, Faecalicoccus, Methanobrevibacter, Mitsuokella, Mobilitalea, Succinivibrio, Gluconobacter, and Plesiomonas after treatment. The abundance of the following genera increased significantly after entecavir treatment in patients with CHB: Clostridium sensu stricto 1, Erysipelotrichaceae UCG-007, and Intestinibacter. The abundance of Streptococcus, Atopobium, and Murdochiella reduced markedly after entecavir treatment in patients with CHB.ConclusionAfter 8-week entecavir treatment, the blood biochemical, immunological, and virological responses improved significantly, the species abundance of intestinal flora increased markedly, and there were unique genera in patients with CHB before and after treatment.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00355-w) contains supplementary material, which is available to authorized users.

Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.

Interpretations of elevated blood levels of alanine aminotransferase (ALT) for drug-induced liver injury often assume that the biomarker is released passively from dying cells. However, the mechanisms driving that release have not been explored experimentally. The usefulness of ALT and related biomarkers will improve by developing mechanism-based explanations of elevated levels that can be expanded and elaborated incrementally. We provide the means to challenge the ability of closely related model mechanisms to generate patterns of simulated hepatic injury and ALT release that scale (or not) to be quantitatively similar to the wet-lab validation targets, which are elevated plasma ALT values following acetaminophen (APAP) exposure in mice. We build on a published model mechanism that helps explain the generation of characteristic spatiotemporal features of APAP hepatotoxicity within hepatic lobules. Discrete event and agent-oriented software methods are most prominent. We instantiate and leverage a small constellation of concrete model mechanisms. Their details during execution help bring into focus ways in which particular sources of uncertainty become entangled with cause-effect details within and across several levels. We scale ALT amounts in virtual mice directly to target plasma ALT values in individual mice. A virtual experiment comprises a set of Monte Carlo simulations. We challenge the sufficiency of four potentially explanatory theories for ALT release. The first of the tested model theories failed to achieve the initial validation target, but each of the three others succeeded. Results for one of the three model mechanisms matched all target ALT values quantitatively. It explains how ALT externalization is the combined consequence of lobular-location-dependent drug-induced cellular damage and hepatocyte death. Falsification of one (or more) of the model mechanisms provides new knowledge and incrementally shrinks the constellation of model mechanisms. The modularity and biomimicry of our explanatory models enable seamless transition from mice to humans.

Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations

BackgroundCOPD exacerbations have negative impact on patients’ survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.MethodsThis is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.ResultsIncluded were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13–41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p < 0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6–3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08–3.1, p < 0.05).ConclusionsLow ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

Prerehabilitation alanine aminotransferase blood levels and one-year mortality rates in older adults following hip fracture.

Low alanine aminotransferase (ALT) blood levels prior to rehabilitation are associated with poor function in older adults following hip fracture. We hypothesized that low ALT blood levels prior to rehabilitation were also associated with one-year mortality in this population. Included were 456 older adults (age ≥ 60 years, 82.5% women) admitted for rehabilitation following hip fracture. ALT blood levels were documented between one and six months prior to rehabilitation. Excluded were patients with ALT blood levels over 40 IU/L possibly consistent with liver injury. The main outcome was all-cause mortality one year following rehabilitation admission. The study group included 142 (31.1%) patients with low (≤10 IU/L) ALT blood levels and the control group included 314 (68.9%) patients with high-normal (11-40 IU/L) ALT blood levels. Overall, 52 (11.4%) patients died within one year following rehabilitation admission. Compared with the control group, patients with low ALT blood levels had significantly higher 1-year mortality rates [17.6 vs. 8.6%, odds ratio 2.27, 95% confidence interval (CI) 1.27-4.08]. Cox regression analysis showed that low ALT blood levels prior to rehabilitation were associated with one-year mortality (hazard ratio 1.88, 95% CI 1.08-3.28) together with age (hazard ratio 1.06, 95% CI 1.02-1.11), independent of gender. However, this association was no longer significant following adjustment also for peripheral vascular disease, admission and discharge functional independence measure scores, albumin serum levels, and length of rehabilitation. In conclusion, low ALT blood levels prior to rehabilitation are associated with one-year mortality in older adults following hip fracture. They may be used when only age and gender are known.

A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals

BackgroundThe gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20–69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.ResultsAmong 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.ConclusionIn a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.Trial registrationClinicalTrials.gov identifier NCT01699893

High-fat diet aggravates the liver disease caused by periodontitis in rats.

Periodontitis is an inflammatory disease that causes periodontium and hepatic alterations. Liver disease is related to the intake of foods rich in fat and sugars (high-fat). The objective of this study was to evaluate whether a high-fat diet can aggravate the liver disease caused by ligature-induced periodontitis in rats. Twenty-one female rats were divided into three groups (n=7 in each group): control; periodontitis (periodontitis induced with ligature) and high-fat + periodontitis (received hypercaloric diet and induction of periodontitis). The rats were submitted to the analyses of the following periodontal parameters: gingival bleeding index (GBI), probing pocket depth (PPD), tooth mobility (TM), and alveolar bone height. In the hepatic tissue, the levels of malondialdehyde (MDA), glutathione (GSH), total cholesterol, and myeloperoxidase activity (MPO) were measured. Liver samples were also histopathologically evaluated. Finally, blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, cholesterol high-density lipoprotein (HDL), and uric acid were measured. The high-fat + periodontitis group presented an increase in the steatosis score (P<0.05) for the histopathologic evaluation, when compared with the periodontitis group. MDA, uric acid and ALT levels also increased, whereas GSH and HDL levels showed lower values. A high-fat diet aggravates the liver disease caused by ligature-induced periodontitis in rats.

Expression and role of TNIP2 in multiple organ dysfunction syndrome following severe trauma.

Severe trauma can result in secondary multiple organ dysfunction syndrome (MODS) and death. Inflammation response and oxidative stress promote the occurrence and development of MODS. TNFAIP3‑interacting protein2 (TNIP2), which can repress the activation of nuclear factor‑κB (NF‑κB) and may be involved in MODS progression, has not been studied in regards to MODS. The present study aimed to investigate the expression, role and mechanism of TNIP2 in MODS following severe trauma. The expression level of TNIP2 was initially detected in the blood of patients with MODS using reverse transcription‑quantitative polymerase chain reaction and western blot assay. Then, to investigate the role of TNIP2 in MODS, a MODS rat model was conducted by trauma and the model rats were treated with TNIP2‑plasmid (intraperitoneal injection). Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatine (Cr) and creatine kinase (CK); and tumor necrosis factorα (TNF‑α), high‑mobility group box1 (HMGB‑1), malondialdehyde (MDA) and total antioxidant capacity (TAC) in the different groups were assessed. In addition, activation of NF‑κB was assessed by detecting the level of phospho‑p65. The results showed that TNIP2 was significantly decreased in the blood of patients with MODS. TNIP2 was also significantly downregulated in the blood and the pulmonary, renal and hepatic tissues of MODS rats. The levels of ALT, AST, LDH, BUN, Cr and CK were markedly increased in the blood of MODS rats, and these increases were inhibited by TNIP2‑plasmid administration. Moreover, blood levels of TNF‑α, HMGB‑1 and MDA were significantly increased in MODS rats, while TAC was notably decreased, and these changes were prevented by TNIP2‑plasmid administration. Furthermore, it was found that activation of NF‑κB induced by MODS was eliminated by TNIP2‑plasmid. In conclusion, the data indicated that TNIP2 is significantly decreased in MODS following severe trauma, and it plays a protective role in MODS development by inhibiting the inflammation response and oxidative stress by preventing NF‑κB activation.

Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice

Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction.Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice.Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein–cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database.Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up- or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia.Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.

Alanine aminotransferase blood levels and rehabilitation outcome in older adults following hip fracture surgery.

Low alanine aminotransferase (ALT) blood levels are associated with frailty and poor outcome in older adults. Therefore, we studied the association between ALT blood levels before rehabilitation and rehabilitation outcome in older adults following hip fracture surgery. A total of 490 older adults (age>60 years, mean age: 82.9±6.7 years, 82.0% women) admitted to rehabilitation following hip fracture surgery were included. The rehabilitation outcome was assessed by Functional Independence Measure (FIM) scores. ALT blood levels were documented between 1 and 6 months before rehabilitation. Patients with ALT blood levels over 40 IU/l possibly consistent with liver injury were excluded. The cohort was divided into two groups: patients with ALT more than 10 IU/l and patients with ALT less than or equal to 10 IU/l. Upon rehabilitation discharge, the FIM outcome measures (motor, cognitive, gain, efficiency) were significantly higher in patients with ALT more than 10 IU/l relative to patients with ALT less than or equal to 10 IU/l (P<0.05). A logistic regression analysis adjusted for age and sex showed that patients with ALT more than 10 IU/l were more likely to have higher (second to fourth upper quartiles) total FIM scores (>50), cognitive FIM scores (>16), and FIM efficiency (>0.228) upon rehabilitation discharge (odds ratio=1.56-1.78). However, this association was no longer significant following adjustment also for admission total FIM score, cognitive impairment, cancer, and albumin serum levels. High-normal ALT blood levels before rehabilitation are associated with a better rehabilitation outcome in older adults following hip fracture surgery. It may be used when data on admission FIM score, cognitive impairment, cancer, and albumin serum levels are not available.