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Abstract Background A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. Methods A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. Results The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and − 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. Conclusions The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

Background: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. Methods: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. Results: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and − 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. Conclusions: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs. [ABSTRACT FROM AUTHOR]

Epstein-Barr Virus (EBV), or Kissing Virus, is a member of the Herpes virus that can be a contributory factor for compromised pregnant, high-risk aborted women worldwide. The present study aimed to detect high-risk EBV by the Monospot test for pregnant, high-risk aborted women, to detect immunoglobulin IgM and IgG for EBV using Enzyme-linked immunosorbent assay (ELISA) technique, to distinguish the infections as acute, chronic, or reactivated, and to determination of Enzymes as Aspartate Transaminase (AST), Alkaline phosphatase (ALP), and Alanine Transaminase (ALT).A cohort of 91 serum samples were collected from high-risk aborted women (ages 15-45 years) who attended Al-Medina Private Laboratory from February to December 2022.Sera were tested for heterophile antibodies(HA) associated with Infectious Mononucleosis (IM) caused by EBV by Latex Agglutination slide test (IM Quick test) and were tested for IgM and IgG antibodies against EBV-CA in serum using the ELISA kit. Sera from the patients and healthy controls were analyzed for Glutamate-Pyruvate Transaminase (GPT), Glutamic Oxaloacetic Transaminase (GOT), Lactate Dehydrogenase (LDH), and Alkaline phosphatase. Compared to healthy controls, the data showed that the late phase with loss and reactivated infection was responsible for 25% of cases and that the acute and late infection cases had a high of 64%. There were significant differences in the level of these hormones;aborted women showed increased levels of serum ALP (70.83) while having a reverse effect with serum ALT (11.7) and AST (25.43). EBV activation was higher in the aborted women. The study would help to determine the role of EBV in the pathogenesis of abortion. [ABSTRACT FROM AUTHOR]

The study was conducted to investigate the effect of use (Lactuca sativa) oil on the body weight and the function of liver through measurement of level ofAspartate Transaminase enzyme (AST), Alanine Aminotransferase enzyme (ALT) and Malonaldehyde enzyme (MAD) and histopathological changes in liver of local male rabbits. 18 rabbits average (1264-1530) gram were divided to 3 groups, every group have 6 local male rabbits, group 1 the control gives only 0.2 ml normal salineorally, and group (2), (3) gives only Lettuce plant oil at (0.1) ml/kg, (0.2) ml/kg respectively orally for (20) day. We conducted that the administration of Lettuce oil producea significance decrease (P< 0.05) at 0.2 ml/kg.b.w. in the body weight and there is a significant increase (P< 0.05) in level of Aspartate Transaminase enzyme and there is a significant increase (P< 0.01) in the level ofAlanine Aminotransferase enzyme and Malonaldehyde enzyme. Furthermore, there is a significant decrease (P< 0.05) at 0.1 ml/kg.b.w. in the level of Aspartate Transaminase enzyme and there is a significant decrease (P< 0.01) in the level of Alanine Aminotransferase enzyme and there is non significant differences (P< 0.01) in the Malonaldehyed enzyme. We concluded that the administration of Lettuce oil in low dose led to produce good effects whereas administration of Lettuce oil with high dose that will produces bad effects in the functionof liver and the body weight of local male rabbits. [ABSTRACT FROM AUTHOR]

Background: Ficus capensis Moraceae and Cnidoscolus aconitifolius Euphorbiaceae leaves have been used separately in traditional medical practice to treat different ailments, of which anemia is one. This study aims to evaluate the effect of F. capensis and C. aconitifolius on hepatic, renal parameters and oxidative stress of phenylhydrazine-induced anemic rats. Methods: Thirty-five rats were randomized into seven groups (A–G) of five rats each. Groups A and B served as the normal control and anemic control, respectively, while Groups C, D, E, F, and G were treated with a standard drug (vitamin B12), 200mg/kg bw. aqueous extract of F. capensis, 400mg/kg b.w. aqueous extract of F. capensis, 200mg/kg bw. of a combination of aqueous extract of F. capensis and C. aconitifolius and 400mg/kg bw. of a combination of aqueous extract of F. capensis and C. aconitifolius, respectively. The biochemical analysis (liver and kidney function analysis, oxidative stress) was carried out using standard diagnostic techniques. Results: The results showed that there was significant decrease (p< 0.05) in the values obtained for Aspartate Transaminase (AST), alanine Transaminase (ALT), Alkaline Phosphatase (ALP), total bilirubin, urea, creatinine, potassium ion, Total Cholesterol (TCHOL), Low-density Lipoprotein (LDL-C), Triglycerides (TRIG), Very Low-density Lipoprotein (VLDL-C) and Malondialdehyde (MDA) and a significant increase (p< 0.05) in obtained values for High-density Lipoprotein (HDL) in all the extract-treated groups compared with the anemic-untreated. The values obtained for most of these biochemical parameters in the extract-treated groups were in the range of the normal control showing that the extract did not, in any way, alter the biochemical parameters. There was a significant increase (p< 0.05) in the glutathione peroxidase (Glut. Perox.) enzyme activity of the groups treated with the aqueous extract of F. capensis and its combination with C. aconitifolius compared with the anemic-untreated. Conclusion: These results suggest that the aqueous extracts of F. capensis and C. aconitifolius leaves may promote liver function parameters, maintain normal serum electrolyte level and kidney function indices, stimulate reduction of "bad cholesterols" and increase "good cholesterol" and reduce oxidative stress. [ABSTRACT FROM AUTHOR]

This study aims to determine the effect of different doses of aspartame on some biochemical changes of liver, sixty of female rats, with age of 60-75 day are used in this study, almost on an average live weight between (200-240 gm). The experiment concentrates on the daily dose, where the animals are randomly divided into four groups, each group contains 15 animals, three experiment groups treated and control group. The first group treatment G1 gavages with aspartame dose (250 mg/kg bw/day), the second group treatment G2 gavages with aspartame dose (500 mg/kg bw/day) and the third group treatment G3 dosage of (750 mg/ kg bw / day), while the control group dosed with 1ml physiologic solution daily (deionized distal water). All the groups had their daily dosages orally for 90 day and the experiment continued from 1 October 2018- 1 January 2019. After the end of experiment, blood sample was collected for estimate the concentration of liver enzymes: Alanine aminotransferase (ALT), Aspartate transaminase (AST) and Lactate dehydrogenase (LDH). The results of this study showed that female rats have significant increase (P> 0.05) in ALT concentration from the treatment groups comparing with control group. There is no significant differences (P >0.05) in the level of AST when it was compared with the control group, while there is significant increase (P> 0.05) in LDH level. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase level. The secondary outcomes were changes in liver stiffness, liver function test parameters, metabolic parameters, and safety. Pooled mean differences and relative risks were calculated using random-effects models. Six hundred studies were screened and eight were included (n = 2413). Semaglutide treatment showed a reduction in serum alanine transaminase [mean difference: 14.07 U/L (95% CI: 19.39 to −8.75); p < 0.001] and aspartate transaminase [mean difference: 6.89 U/L (95% CI: 9.14 to −4.63); p < 0.001] levels. There was a significant improvement in liver fat content [mean difference: 4.97% (95% CI: 6.65 to −3.29); p < 0.001] and liver stiffness [mean difference: 0.96 kPa (95% CI: 1.87 to −0.04); p = 0.04]. There were significant improvements in the glycated hemoglobin level and the lipid profile. However, the risk of serious adverse events [relative risk: 1.54 (95% CI: 1.02 to 2.34); p = 0.04] was high following semaglutide treatment as compared to placebo; the most common ones were gastrointestinal (nausea and vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) and gallbladder-related diseases. Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with NAFLD/NASH. However, the gastrointestinal adverse effects could be a major concern. • Semaglutide could be used in patients with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. • It significantly improves liver enzymes, reduces liver stiffness, and improves metabolic parameters in these patients. • Gastrointestinal adverse effects and gallbladder-related diseases could be a major concern. [ABSTRACT FROM AUTHOR]

Fluoride, as the super reactive element fluorine, is found naturally throughout earth's crust. It has been identified as a strong, persistent powerful cumulative toxic agent, commonly distributed in the rivers, lakes, seas of earth. It is highly mobile and biologically active element in aquatic systems. Fish are considered as the excellent and valuable bioindicator of ecosystem pollution. The present study was designed to estimate acute fluoride toxicity on enzyme activity of liver of freshwater fish Tilapia mossambica. The major enzymes of Carbohydrate - Protein Metabolic pathways are Alkaline phosphatase (ALP), Alanine transaminase (ALT), Aspartate transaminase (AST) in association with carbohydrate, protein, lipid in the liver of Tilapia mossambica, from Kalri Lake (Keenjhar Lake), Sindh, Pakistan at low amount of fluoride (sub-lethal) was estimated by using UV- Visible Spectrophotometer. Results showed ALP, AST and ALT enzymes present in the liver tissue were significantly changed (p < 0.001). Finally, it is concluded that fluoride produces the adverse poisonous effect on liver functioning which may be associated with altered or elevated enzyme activity of protein-carbohydrate metabolism.

Purpose: To illustrate whether De Ritis (aspartate transaminase-AST/alanine transaminase-ALT) ratio is useful in risk stratification of localized prostate cancer and propose an easy predictive model for biochemical recurrence-free survival (BCRFS). Methods: In total, 438 patients who underwent radical prostatectomy were included in this study. Blood samples including AST and ALT were collected 1-7 days before surgery. An elevated AST and ALT value was defined as over 40 or 56 IU/L. Results: The median AST and ALT value was 18.5 (16-22) and 14 (11-18) IU/L. In total, 15 patients (3.4%) and 9 patients (2.1%) exhibited elevated AST value and ALT value. The median De Ritis ratio was 1.33 (1.11-1.60), and ROC curve indicated the best cutoff of 1.325 in predicting the occurrence of biochemical recurrence. Higher De Ritis ratio was found to be related to older age ( p < 0.001), higher tumor stages ( p < 0.001) and Gleason Score ( p < 0.001), presence of seminal invasion ( p < 0.001), positive surgical margin ( p < 0.001) and lymph node metastasis ( p = 0.003). Multivariate logistic regression confirmed that De Ritis ratio was an independent predictor for final Gleason Score ( p < 0.001), and multivariate Cox regression demonstrated De Ritis ratio as an independent risk factor for BCRFS. A simple predictive model which incorporated De Ritis ratio, pathological tumor stage and final Gleason Score could help risk stratification for BCRFS. Conclusion: Higher De Ritis ratio could be predictive for worse pathological outcomes and higher BCR in localized prostate cancer patients. A predictive model which incorporates De Ritis ratio, Gleason Score and pathological tumor stage could help risk stratification for BCRFS. [ABSTRACT FROM AUTHOR]

Aim: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 4 mg saroglitazar treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH)., Methods: PubMed, Embase, Scopus, Cochrane CENTRAL, medRxiv (pre-print), bioRxiv (pre-print), and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase (ALT) level. The secondary outcomes were changes in liver stiffness, liver function test parameters, and metabolic parameters. Pooled mean differences were calculated using random-effects models., Results: Of 331 studies that were screened, ten were included. Treatment with adjunct saroglitazar showed a reduction in ALT [mean difference: 26.01 U/L (95% CI: 10.67 to 41.35); p = 0.009; i 2 : 98%; moderate GRADE evidence] and aspartate transaminase [mean difference: 19.68 U/L (95% CI: 8.93 to 30.43); p<0.001; i 2 : 97%; moderate GRADE evidence] levels. There was a significant improvement in liver stiffness [mean difference: 2.22 kPa (95% CI: 0.80 to 3.63); p = 0.002; i 2 : 99%; moderate GRADE evidence]. There were significant improvements in glycated hemoglobin [mean difference: 0.59% (95% CI: 0.32 to 0.86); p<0.001; i 2 : 78%; moderate GRADE evidence], total cholesterol [mean difference: 19.20 (95% CI: 1.54 to 36.87); p = 0.03; i 2 : 95%; moderate GRADE evidence], and triglyceride [mean difference: 105.49 mg/dL (95% CI: 11.18 to 199.80); p = 0.03; i 2 : 100%; moderate GRADE evidence] levels. Saroglitazar treatment was safe., Conclusion: Treatment with adjunct 4 mg saroglitazar could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters (serum glucose and lipid profile) in patients with NAFLD or NASH., Competing Interests: Declaration of Competing Interest I/we declare no competing interests., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Laparoscopic cholecystectomy (LC) is gold standard treatment for cholelithiasis. This surgical procedure requires insufflation of carbon dioxide into peritoneal cavity. Intra-abdominal pressure increases, causing disturbances on blood flow of the portal vein with secondary liver injury. In this study we evaluated the hepatic function in 147 patients who underwent laparoscopic cholecystectomy. Three liver biomarkers have been measured 24 hours before and 24 hours after the surgery: Aspartate transaminase (AST), Alanine transaminase (ALT) and total bilirubin. The results show significantly increased levels of all 3 biomarkers, 24 hours after the surgery. We also found a correlation between surgery duration and levels of serum AST, ALT and bilirubin. The highest levels of hepatic enzymes and total bilirubin were recorded in patients with maxim of minutes (80-90) under pneumoperitoneum. [ABSTRACT FROM AUTHOR]

Compared to data on adolescents and adults, limited research has been conducted on biological correlates among young children with possible psychological difficulties, especially in Asian countries. By focusing on various peripheral biochemical indicators, we investigated potential biological correlates of psychological states in a community sample of Taiwanese school children aged 6-10 years. In total, 307 students (159 obese children and 148 normal-weight children) were selected from first- and fourth-grade school children in eight elementary schools in the Taipei metropolitan area in 2009. These children underwent a comprehensive health examination, including a physical examination, blood sample analysis, and questionnaire administration in a hospital. Differences in anthropometric and serum biochemical readings were compared between children with average and worse levels on each of the five psychological domains. We found that interleukin (IL)-1β [ β = 1.29, 95 % confidence interval ( CI) 0.50-2.09], IL-10 ( β = 1.61, 95 % CI <0.01-3.24), fasting blood glucose ( β = 0.08, 95 % CI 0.01-0.15), homocysteine ( β = 0.63, 95 % CI 0.09-1.18), and aspartate transaminase (AST) ( β = 0.15, 95 % CI <0.01-0.31) were significantly positively associated with anxiety. In addition, IL-1β, insulin, AST, and alanine aminotransaminase (ALT) were significantly positively associated with depression. Anger and disruptive behaviors were also related to specific biological correlates. Specific biological correlates, including AST/ALT, cardiovascular disease-related variables, and specific cytokines, were linked to particular psychological states among young children in this Asian population. These might provide a route for better understanding the biological aspects of children's mental health and might contribute to research on diagnostic or predictive biomarkers for psychiatric diseases in young children. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Khaya senegalensis A. Juss (Meliaceae) is commonly exploited for the traditional treatment of diabetes mellitus in Nigeria and Togo. The present study was conducted to examine the anti-diabetic activity of Khaya senegalensis butanol fraction (KSBF) of root ethanolic extract in a type 2 diabetes (T2D) model of rats. Materials and methods: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40mg/kg body weight) and the animals were treated with 150 and 300mg/kg body weight (BW) of the fraction for five days in a week. Relevant diabetes-related parameters were analyzed in all experimental animals. Results: The KSBF treatment, at 300mg/kg BW, significantly (p<0.05) reduced blood glucose level, improved oral glucose tolerance ability and ?-cell function (HOMA-?), decreased insulin resistance (HOMA-IR), stimulated hepatic glycogen synthesis, ameliorated serum lipids alterations and prevented hepatic and renal damages compared to untreated diabetic rats. Additionally, the fraction insignificantly (p>0.05) improved weight gain, decreased food and fluid intake, stimulated insulin secretion and lowered serum fructosamine concentrations compared to untreated diabetic rats. Conclusions: Data from this study suggests that orally administered KSBF, at 300mg/kg BW, possess remarkable anti-type 2 diabetic activity and could ameliorate some diabetes-associated complications and hence can be considered as a source of potential anti-type 2 diabetic medicine. [Copyright &y& Elsevier]

Highlights: [•] Fermented P. ribis mycelia (FPM) have been approved by NHFPC for use as a new food material. [•] We evaluated acute and subchronic toxicity in experimental animal of FPM. [•] Maximum Tolerated Dose (MTD) of FPM for male and female mice was over 10g/kg bw. [•] No Observed Adverse-Effect Level (NOAEL) of the test material was greater than 8.7g/kg bw/day in both sexes of rats. [Copyright &y& Elsevier]

Highlights: [•] We monitored the effects of subchronic exposure to furan on the male reproductive system. [•] Serum testosterone levels were increased serum LH was decreased. [•] There were no changes in 17-OHase, 3β-HSD and 17β-HSD activities or serum FSH. [•] The mRNA level for StAR was increased by all doses of furan. [•] The mRNA for Cyp11a1 and intratesticular testosterone were increased by furan. [•] We conclude that subchronic furan exposure affects testicular steroidogenesis. [Copyright &y& Elsevier]

Abstract: Aims: Preventive and/or therapeutic interventions using natural products for ischemic heart disease have gained considerable attention worldwide. This study investigated the cardioprotective effect and possible mechanism of embelin, a major constituent of Embelia ribes Burm, using isoproterenol (ISO)-induced myocardial infarction model in rats. Materials and methods: Rats were pretreated for three days with embelin (50mg/kg, p.o) before inducing myocardial injury by administration of ISO (85mg/kg) subcutaneously at an interval of 24h for 2 consecutive days. Serum was analyzed for cardiac specific injury biomarkers, lipids and lipoprotein content. Heart tissues were isolated and were used for histopathology, antioxidant and mitochondrial respiratory enzyme activity assays and western blot analysis. Key findings: Results showed that pretreatment with embelin significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB, LDH and AST), serum levels of lipids and lipoproteins and histopathological changes when compared to ISO-induced controls. Exploration of the underlying mechanisms of embelin action revealed that embelin pretreatment restored the myocardial mitochondrial respiratory enzyme activities (NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity), strengthened antioxidant status and attenuated ISO-induced myocardial lipid peroxidation. Immunoblot analysis revealed that embelin interrupted mitochondria dependent apoptotic damage by increasing the myocardial expression of Bcl-2 and downregulating the expression of Bax, cytochrome c, cleaved-caspase-3 & 9 and PARP. Histopathology findings further strengthened the cardioprotective findings of embelin. Significance: Result suggested that embelin may have a potential benefit in preventing ischemic heart disease like myocardial infarction. [Copyright &y& Elsevier]

Background & Aims: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. Methods: We evaluated a cohort of PBC patients (n=386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response. A validation cohort was provided through well-characterised patients attending the Toronto Center for Liver Diseases (n=479) and Jena University Hospital (n=150). Results: On multivariate analysis, factors at diagnosis associated with liver transplant (LT)/death were patient age (HR:1.06; p <0.001), elevated bilirubin (HR:1.27; p <0.001), early-onset cirrhosis (HR:2.40; p <0.001) and baseline AST/platelet ratio index (APRI) (HR:1.95; p <0.001). At 1-year, UDCA biochemical non-response predicted poorer transplant-free survival, and additional factors (multivariate) associated with adverse outcome were age (HR:1.02; p <0.05) and 1-year APRI (HR:1.15; p <0.001). Obtaining a cut-point from our derivation cohort, APRI >0.54 at baseline was predictive of LT/death (adjusted HR: 2.40; p <0.001), and retained statistical significance when applied at 1-year (APRI-r1, adjusted HR:2.75; p <0.001) despite controlling for UDCA-response. Across both cohorts, transplant-free survival was poorer for biochemical-responders with an APRI-r1 >0.54 vs. biochemical-responders with a lower APRI-r1 (p <0.01 and p <0.001, respectively); non-responders with high APRI-r1 had the poorest outcomes (p <0.001 and p <0.001). Conclusion: In PBC, elevated APRI is associated with future risk of adverse events, independently and additively of UDCA-response. This cross-centre, robustly validated observation will contribute to ongoing efforts to refine existing risk-stratification tools, as well as direct focus for new therapies in patients with PBC. [Copyright &y& Elsevier]

Abstract: Dysregulation of adipose hormones in obesity has been associated with the hastened development of metabolic syndrome and associated chronic disease sequalae including cardiovascular disease and type 2 diabetes mellitus. This study aims to identify common biochemical and anthropometric markers that impact adipose hormones, including adiponectin and leptin. Based on previous literature, it was hypothesized that these would be adversely impacted by liver function parameters, and adiponectin levels would be positively correlated with phospholipid Ω-3 fatty acids. Forty nondiabetic adult subjects (body mass index, ≥25.0 kg/m2) were recruited. Fasting plasma samples were taken to assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and blood lipids. Basic anthropometric measurements were also recorded. Adiponectin levels were positively correlated with high-density lipoprotein cholesterol and negatively correlated with anthropometric measures, insulin, liver enzymes, triglycerides, and very low–density lipoprotein cholesterol but not body mass index. Conversely, plasma leptin levels were positively correlated with anthropometric measures, C-reactive protein, high-density lipoprotein cholesterol, and plasma phospholipid proportions of Ω-3 α linoleic acid but inversely correlated with creatinine levels. These results support other data regarding correlations between adiponectin and relative adipose distribution. Correlations with specific liver enzymes may indicate that adiponectin levels are tied to fatty acid deposition in the liver; however, liver/kidney damage though further mechanistic clarification is required. Leptin levels were associated with measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids, may serve as potential future therapeutic targets for the prevention and management of obesity and related comorbidities. [Copyright &y& Elsevier]

Background & Aims: Obesity and its related pathologies, such as hepatic steatosis, are associated with chronic inflammation and insulin resistance (IR), which contribute to cardiovascular disease. Our previous studies indicated that Spondin 2 has a protective role in the context of cardiovascular and cerebrovascular diseases. Whether Spondin 2 is also associated with the development of hepatic steatosis and IR remains unclear. Methods: Wild-type mice, Spondin 2-knockout (KO) mice, hepatic-specific Spondin 2 transgenic (Spondin 2-TG) mice, high fat diet (HFD)-induced obese mice injected with an adenovirus expressing Spondin 2-specific shRNA or a Spondin 2 mutant and genetically obese (ob/ob) mice injected with an adenovirus expressing Spondin 2 were fed normal chow (NC) or HFD for indicated time to induce obesity, hepatic steatosis, inflammation, and IR. Biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations in these mice. The molecular mechanisms of Spondin 2 functions were explored in mice and in hepatocytes or cell lines. Results: Consistent with Spondin 2 repression in the livers of HFD-induced and ob/ob mice, the Spondin 2-KO or hepatic-specific Spondin 2 knockdown mice exhibited more severe obesity, hepatic steatosis, inflammation, and IR upon HFD. Conversely, these pathological conditions were significantly improved in the Spondin 2-TG mice or Spondin 2-overexpressing ob/ob mice. Spondin 2 interacts with PPARα to regulate PPARα-target genes, thereby improving the pathological phenotypes. In contrast, the hepatic overexpression of mutant Spondin 2 without the PPARα-interacting domain failed to improve the aggravated phenotypes observed in the Spondin 2-KO mice. Conclusion: Spondin 2 regulates hepatic lipid metabolism and alleviates hepatic steatosis, obesity, inflammation, and IR in mice via its interaction with PPARα. [Copyright &y& Elsevier]

Background & Aims: Cardiotrophin-1 (CT-1) is a hepatoprotective cytokine that modulates fat and glucose metabolism in muscle and adipose tissue. Here we analyzed the changes in hepatic fat stores induced by recombinant CT-1 (rCT-1) and its therapeutic potential in non-alcoholic fatty liver disease (NAFLD). Methods: rCT-1 was administered to two murine NAFLD models: ob/ob and high fat diet-fed mice. Livers were analyzed for lipid composition and expression of genes involved in fat metabolism. We studied the effects of rCT-1 on lipogenesis and fatty acid (FA) oxidation in liver cells and the ability of dominant negative inhibitor of AMP-activated protein kinase (AMPK) to block these effects. Results: CT-1 was found to be upregulated in human and murine steatotic livers. In two NAFLD mouse models, treatment with rCT-1 for 10days induced a marked decrease in liver triglyceride content with augmented proportion of poly-unsaturated FA and reduction of monounsaturated species. These changes were accompanied by attenuation of inflammation and improved insulin signaling. Chronic administration of rCT-1 caused downregulation of lipogenic genes and genes involved in FA import to hepatocytes together with amelioration of ER stress, elevation of NAD+/NADH ratio, phosphorylation of LKB1 and AMPK, increased expression and activity of sirtuin1 (SIRT1) and upregulation of genes mediating FA oxidation. rCT-1 potently inhibited de novo lipogenesis and stimulated FA oxidation in liver cells both in vitro and in vivo. In vitro studies showed that these effects are mediated by activated AMPK. Conclusions: rCT-1 resolves hepatic steatosis in obese mice by mechanisms involving AMPK activation. rCT-1 deserves consideration as a potential therapy for NAFLD. [Copyright &y& Elsevier]

Highlights: [•] TCBQ-intoxication elevated ALT, AST activities and TBIL content. [•] TCBQ-intoxication induced necrosis and inflammatory in liver section. [•] TCBQ-intoxication increased ROS, TBARS and decreased antioxidant activities. [•] TCBQ-intoxication induced HO-1 and NQO1 expression. [•] Pretreatment of CGA relieved TCBQ-induced liver damage remarkably. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Senna singueana is currently used in the traditional treatment of diabetes mellitus in Nigeria. The present study examined the anti-diabetic activity of the Senna singueana acetone fraction (SSAF) of stem bark in a type 2 diabetes (T2D) rat model. Materials and methods: Crude ethyl acetate extract of the Senna singueana stem bark was fractionated with various solvents and the acetone fraction was selected for in vivo studies based on the high ?-glucosidase and ?-amylase inhibitory activities. In the in vivo study, male Sprague-Dawley rats were induced with T2D and treated with the SSAF at 150 and 300mg/kg body weight. Several T2D-related parameters were measured in the study. Results: After 4 weeks of intervention, non-fasting blood glucose concentrations were significantly decreased and the glucose tolerance ability was significantly improved in the SSAF treated groups compared to the diabetic control group. Serum insulin concentrations, pancreatic ?-cell function (HOMA-?) and liver glycogen were significantly (P<0.05) increased while serum alanine transaminase, alkaline phosphatase and urea were significantly decreased in the SSAF treated diabetic rats compared to the diabetic control group. Though insignificantly (P>0.05), other T2D-induced abnormalities such as food and fluid intake, body weight, serum lipids, serum fructosamine level and peripheral insulin resistance (HOMA-IR) were also partially ameliorated by the SSAF treatment. Conclusion: Data of this study suggest that orally administered SSAF could ameliorate most of the T2D-induced abnormalities in a T2D model of rats. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Tinospora cordifolia (Willd.) Miers is an important constituent of several ayurvedic medicinal preparations. In Ayurveda it is mentioned as “rasayan” and traditionally used for the treatment of asthma, chronic cough besides other ailments. This study was carried out to study the mechanisms involved in protection accorded by extract of Tinospora cordifolia (Tc) stem to asthmatic mice by regulation of oxidative stress, pro-inflammatory mediator release and redox signaling involving NFκB. Materials and methods: BALB/c mice were sensitized with intraperitoneal (i.p.) Ovalbumin (Ova) on days 0 and 14, followed by intranasal Ovalbumin (Ova) challenge on days 24 and 27 to generate an in vivo asthma model. Tc extract (hydroalcoholic, 100mg/kg) and dexamethasone (1mg/kg) were given orally from day 15 to 23 to the Tc+Ova treated group and Dex+Ova treated group respectively. Oxidative stress parameters e.g. activity of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase, lipid peroxidation, GSH/GSSG ratio, protein carbonyl content, eosinophil peroxidase, myeloperoxidase activity, and NO release were measured in tissue, blood and bronchoalveolar lavage fluid (BALF). Estimation of cytokines was done in BALF. Western blot analysis was done for IκB α, iNOS, COX-2, iCAM-1 and pJNK MAPKs along with histopathology. Results: Tc extract treated mice showed decreased airway hyper-responsiveness, eosinophil count and IgE content in blood as compared to Ova treated asthmatic mice. Increase in activities of SOD, catalase, glutathione reductase, glutathione peroxidase as well as GSH/GSSG ratio was observed while a decrease in MDA formation, protein carbonyl content, eosinophil peroxidase, myeloperoxidase activity and NO release in BALF was seen in Tc treated mice. In BALF, levels of cytokines IL-4 and TNF-α were reduced and IFN-γ levels increased in extract treated mice. At the same time Tc treatment of Ova-challenged mice significantly increased the level of IκB α, cytosolic inhibitor of redox sensitive transcription factor NFκB. Immunoblot analysis revealed considerable decrease in the levels of COX-2, ICAM-1, iNOS, and pJNK. Histopathology and PAS staining also indicate a protective effect of Tc extract in inflammation and mucus hyper-secretion due to goblet cell hyperplasia. Conclusion: The results suggest a protective effect of Tc extract against oxidative stress, pro-inflammatory mediator release and redox signaling in the murine model of asthma. The Tc extract shows therapeutic potential for management of asthmatic inflammation and other lung inflammatory conditions. [Copyright &y& Elsevier]

Highlights: [•] Beneficial effect of NHDC on CCl4-induced acute oxidative injury was discussed. [•] NHDC significantly ameliorated oxidative damage in mice liver and serum. [•] NHDC significantly suppressed oxidative damage in HepG2 cells. [•] NHDC is a powerful antioxidant and is a potential hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored. Methodology: A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study. Results: Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory. Conclusion: Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up. [Copyright &y& Elsevier]

Abstract: The present study was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against CCl4-induced hepato-toxicity in mice. The mice were orally administrated with TSDN for seven days and then given CCl4 (0.3%, 10ml/kg i.p.). The results showed that TSDN significantly attenuated the activities of ALT and AST, consistent with hematoxylin–eosin staining. The ALP levels and relative liver weight were significantly decreased by TSDN compared with model group. Moreover, TSDN dramatically decreased MDA, iNOS and NO levels, while the levels of GSH, GSH-Px and SOD were increased. Further investigations showed that TSDN inhibited CCl4-induced metabolic activation and CYP2E1 expression, down-regulated the levels of MAPKs phosphorylation, NF-κB, HMGB1, COX-2 as well as effectively suppressed the expressions of Caspase-3, Caspase-9, PARP and Bak. Quantitative real-time PCR assay demonstrated that TSDN obviously decreased the gene expressions of TNF-a, IL-1β, IL-6, IL-10, Fas, FasL, Bax as well as modulated Bcl-2 mRNA level. This is the first time to report the protective actions of the TSDN against CCl4-induced liver damage in mice through suppression of inflammation and apoptosis. This natural product should be developed as a new drug for treatment of liver injury in future. [Copyright &y& Elsevier]

Highlights: [•] CYP2E1 and NAT2 gene plays an important role in determining the hepatotoxicity. [•] We used HRM analysis in tuberculosis patients of Western Indian population. [•] We report 18 novel SNPs, 3 in 5′-UTR, 14 in exonic and 1 in intronic region. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mammals display a differential pattern of cyanide detoxification capabilities (CDC) across species and tissues. [•] Plasma CDC decreases in proportion to total plasma proteins in non-human primates. [•] Nervous system CDC may be impaired by dietary deficiency in sulfur amino acids and/or exposure to cyanide or cyanate. [•] Susceptibility to cyanide poisoning may be modified by diet and endogenous tissue variations in CDC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This guideline summarizes the quality of the evidence to date and provides a reasonable approach to the diagnosis, evaluation and treatment of the hypertensive disorders of pregnancy (HDP). Evidence: The literature reviewed included the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines from 2008 and their reference lists, and an update from 2006. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT) and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2006 and March 2012. Articles were restricted to those published in French or English. Recommendations were evaluated using the criteria of the Canadian Task Force on Preventive Health Care and GRADE. [Copyright &y& Elsevier]

Abstract: Objective: This study investigated the effects of scopoletin on alcohol-induced hepatic lipid accumulation in diet-induced obese mice and its mechanism. Material/Methods: Alcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without scopoletin (0.05%, wt/wt). Results: Scopoletin reduced plasma acetaldehyde, fatty acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and droplets and fasting blood glucose levels that were increased by alcohol. Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to the alcohol control group. Moreover, scopoletin significantly inhibited hepatic CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH-Px and GST and the levels of GSH compared to the alcohol control group. The hepatic lipid peroxide level was significantly lowered by scopoletin supplementation in alcohol-administered obese mice. Conclusions: Taken together, these results suggested that scopoletin can ameliorate alcohol-induced hepatic lipid accumulation by modulating AMPK–SREBP pathway-mediated lipogenesis in mice fed a high-fat diet. [Copyright &y& Elsevier]

Abstract: Isoliquiritigenin (ISL), a chalcone and liquiritigenin (LTG), a flavonoid found in licorice roots and several other plants. ISL displays antioxidant, anti-inflammatory, antitumor and hepatoprotective activities whereas LTG is an estrogenic compound, acts as an agonist selective for the β-subtype of the oestrogen receptor. Both the phenolics were isolated from the rhizomes of Glycyrrhiza glabra. Five derivatives from ISL and four derivatives from LTG were synthesized. All the compounds were established by extensive spectroscopic analyses and screened through oral glucose tolerance test to gain preliminary information regarding the antihyperglycemic effect in normal Swiss albino male mice. ISL (1), ISL derivatives 3, 4, 5, 7 and LTG derivatives 9 and 10 showed significant blood glucose lowering effect. The structure–activity relationship indicated that the presence of ether and ester groups in ISL and LTG analogues are important for exhibiting the activity. Compounds 1, 4 and 10 were selected for in vivo antidiabetic activity and found to be potential candidates for treatment of diabetes. It is the first report on antidiabetic activity of ISL derivative 4 and LTG derivative 10. [Copyright &y& Elsevier]

Abstract: The study was designed to investigate the immune-modulatory effects of triptolide (TP) on CD4+ T cell responses during liver injury. Previous studies have suggested that TP plays a critical role in modulating both innate and adaptive immune reactions, but its effects on the Th17/Treg balance during TP-induced liver injury remain unknown. In this study, female C57BL/6 mice were administered by oral gavage with TP at a dose of 250 or 500μg/kg per mouse. We examined the plasma biochemical parameters, histopathological changes, hepatic frequencies of Th17 cells and Treg cells, hepatic expression of transcriptional factors and cytokine genes and hepatic interleukin (IL)-17 and IL-10 levels in TP-administered mice. Mice treated with TP displayed liver injury with markedly increased plasma transaminase as well as hepatic mRNA expression of retinoid related orphan receptor (ROR)-γt and hepatic IL-17 level at 24h. However, hepatic frequencies of Tregs and hepatic expression of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) decreased at 24h after TP administration. Furthermore, we found that elevated serum biochemical parameters positively correlated with the Th17/Treg ratios. Taken together, these results revealed a novel and interesting phenomenon of TP in the enhancement of the expansion of Th17 cells and suppression of the production of Tregs during liver injury, which may represent a new pathogenesis of TP-induced liver injury. [Copyright &y& Elsevier]

Highlights: [•] Tim-3 was increased in CD4+CD25+ Foxp3+ regulatory T cells. [•] Blocking the Tim-3/galectin-9 pathway resulted in the suppression of Tregs in vitro, thereby significantly increasing interferon (IFN)-γ production from hepatic Teffs. [•] Blockade of Tim-3 in vivo with an anti-Tim-3 antibody exacerbated the acute hepatitis possibly by increased IFN-γ production. [•] In vitro activation of CD4+CD25− T cells with the T cell receptor (TCR) plus interleukin 2 (IL-2) up-regulated Tim-3 expression. [ABSTRACT FROM AUTHOR]

Background & Aims: Many of the beneficial effects of ω3-fatty acids (ω3FAs) are being attributed to their anti-inflammatory properties. In animal models, ω3FAs also protect from hepatic ischemia reperfusion injury (IRI), a significant cause of complications following liver surgery. Omegaven®, a clinical ω3FA-formulation, might counteract the exaggerated inflammatory response underlying IRI, but the according mechanisms are unresearched. Recently, GPR120 has been identified as a first receptor for ω3FAs, mediating their anti-inflammatory effects. Here, we sought to investigate whether Omegaven® protects from hepatic IRI through GPR120. Methods: Using a mouse model of liver IRI, we compared the effects of a GPR120 agonist with those of Omegaven®. Results: GPR120 in liver was located to Kupffer cells (KCs). Agonist and Omegaven® provided similar protection from IRI, which was abolished by clodronate-depletion of KCs or by pretreatment with an αGpr120-siRNA. In vitro and in vivo, both agents dampened the NFκB/JNK-mediated inflammatory response. Dampening was associated with an M1>M2 macrophage polarization shift as assessed by marker expression. In αGpr120-siRNA-pretreated mice with or without ischemia, Omegaven® was no more able to promote M2 marker expression, indicating its anti-inflammatory properties are dependent on GPR120 in liver. Conclusions: These findings establish KC-GPR120 as a key mediator of Omegaven® effects and suggest GPR120 as a therapeutic target to mitigate inflammatory stress in liver. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Cydonia oblonga Mill. leaves are traditionally used in Uyghur medicine to treat or prevent cardiovascular disease. Beyond a demonstrated effect on thrombosis, we tested it for an effect on dyslipidemia, in a rat model of hyperlipidemia. Methods: Seventy healthy Sprague Dawley rats were randomly divided into 6 groups: normal controls, model controls, simvastatin, and low-, medium- and high-dose Cydonia oblonga Mill. leaf extracts (COM), orally for 56 days. The normal controls were fed a normal diet, all other groups a high fat diet. Rat weights were recorded over time. Total cholesterol (TC), triglycerides (TG), low and high-density lipoproteins (LDL, HDL), as well as AST, ALT and total protein (TP) were measured in serum at the end of the study. The antioxidant capacity of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA) was measured in liver samples, along with lipoprotein lipase (LPL), and hepatic lipase (HL). Liver pathology was described. Results: COM dose-dependently reduced TC, TG, LDL-C and MDA, inhibited the activity of ALT, AST and LPS, increased HDL-C content, increased the activity of SOD, GSH-PX, LPL and HL, and reduced liver steatosis in hyperlipidaemia rats, which was significant at medium and high doses. The effect of COM was similar to that of simvastatin except for increased LPL and HL which were reduced by COM but not by simvastatin. Conclusion: Cydonia oblonga Mill. leaf extracts have hypolipidaemic and hepatoprotective effects, probably related to increasing antioxidant capacity and lipoprotein metabolism in the liver, and inhibition of lipogenesis. [Copyright &y& Elsevier]

Abstract: To investigate the mechanisms by which the anticancer drug doxorubicin (DOX)-induced hepato-renal damage could be prevented by the cholesterol-lowering statin, atorvastatin (Ator), Ator (10mg/kg) was administered orally for 10days, and, in independent rat groups, DOX hepato-renal toxicity was induced via a single i.p. dose of 15mg/kg at day 5 of experiment, with or without Ator. DOX caused deterioration in hepato-renal function, as it significantly increased blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT) and aspartate transaminase (AST) compared to control, with distortion in normal renal and hepatic histology. Pretreatment with Ator preserved kidney and liver function and histology. DOX caused oxidative stress as indicated by significant decrease in reduced glutathione (GSH) level and catalase activity with increase in malondialdehyde (MDA) compared to control. Combined DOX/Ator significantly reversed these values compared to DOX in both kidney and liver. DOX caused nitrosative stress, as it increased tissue nitric oxide compared to control. Concomitant DOX/Ator treatment decreased NO in kidney and liver. Furthermore, DOX caused inflammatory effects indicated by up-regulation of hepato-renal nuclear factor-κB (NF-κB) expression and increment of tumor necrosis factor-α (TNF-α) tissue concentration, with down-regulation of endothelial nitric oxide synthase (eNOS). DOX also caused apoptotic effect, as it up-regulated the apoptotic marker, Bcl-2-associated X protein (Bax), expression in liver and kidney. Using Ator with DOX reversed hepato-renal inflammatory and apoptotic marker expression. These findings suggest Ator as a protective adjuvant against DOX toxicity, via antioxidant, anti-nitrosative, anti-inflammatory and anti-apoptotic mechanisms. [Copyright &y& Elsevier]

Highlights: [•] Yellow pigments monascin (MS) and ankaflavin (AK) are secondary metabolites derived from Monascus-fermented products. [•] MS and AK prevented fatty acid accumulation in oleic acid-induced steatosis in hepatocytes. [•] MS and AK attenuated high-fat diet-induced nonalcoholic fatty liver disease in mice. [•] MS and AK act as PPARα agonists to increase AMPK activity and beta-oxidation in hepatocytes. [Copyright &y& Elsevier]

Objective: Irisin is a recently discovered myokine proposed to increase thermogenesis-related energy expenditure and improve metabolism. We aimed to comparatively evaluate serum irisin levels in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association with disease severity. Methods: Fifteen and 16 consecutively enrolled patients with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were recruited. Irisin, established adipokines and biochemical tests were measured. Results: Serum irisin levels were statistically different in obese controls (33.7±2.7ng/mL; p<0.001) and patients with NAFL (30.5±1.5ng/mL; p<0.001) and NASH (35.8±1.9ng/mL; p=0.001) compared with lean controls (47.7±2.0ng/mL), but were similar among patients with NAFL, NASH and obese controls. This difference remained significant after adjustment for body mass index (or waist circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI), exercise and time since blood collection. Serum leptin and adiponectin, but not irisin, levels were independently from BMI correlated with insulin resistance and cardiometabolic factors. Serum irisin tended to be higher in patients with (36.7±2.4ng/mL) than without (30.8±1.2ng/mL; p=0.02) portal inflammation and independently associated with the latter; these data need to be confirmed by future studies. Conclusions: Serum irisin levels differ between lean controls and obese controls or NAFLD patients. Despite similar circulating irisin levels between NAFL and NASH groups, irisin may be independently and positively associated with the presence of portal inflammation. Future clinical and mechanistic studies are needed to confirm and extend these data. [ABSTRACT FROM AUTHOR]

Abstract: It is widely known that hepatitis and its complications such as cirrhosis or hepatocellular carcinoma are one of the major health problems of the world especially since no specific treatment is available. In the present study we investigated the hepatoprotective potential of the methanolic extract of the whole plant of Dodonaea viscosa and its ethyl acetate, aqueous, butanol and n-hexane fractions against carbon tetrachloride (CCl4) induced hepatoxicity in rats. Hepatoprotection was assessed in terms of reduction in serum enzymes (ALT, AST, and ALP) that occur after CCl4 injury, and by histopathology and immunohistochemistry. The methanolic extract reduced the serum enzyme level (ALT, AST, and ALP) down to control levels despite CCl4 treatment. It also reduced the CCl4-induced damaged area to 0% as assessed by histopathology. The CD68+ macrophages were also reduced in number around the central vein area by the methanolic extract. These hepatoprotective effects were better than the positive control silymarin. Similar hepatoprotective activities were found with the ethyl acetate, and aqueous fractions of the methanolic extract. The butanol and n-hexane fractions showed elevated levels of ALT, AST and ALP as compared to the positive control silymarin. Histopathology showed ∼30% damage to the liver cells with the butanol and n-hexane fractions which still showed some protective activity compared to the CCl4 treated control. HPLC fingerprinting suggested that hautriwaic acid present in the methanolic extract and its ethyl acetate, and aqueous fractions may be responsible for this hepatoprotective activity of Dodonaea viscosa which was confirmed by in vivo experiments. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Eucommia ulmoides Oliv. (Family Eucommiaceae), also known as Dù-zhòng (Chinese: ▪), Tuchong (in Japanese), is the sole species of the genus Eucommia. The leaf, stem, and bark as well as staminate flower of Eucommia ulmoides have been traditionally used to cure many diseases in China, Japan, Korea, among others. The aim of this review is to comprehensively outline the botanical description, ethnopharmacology, phytochemistry, biological activities, and toxicology of Eucommia ulmoides and to discuss possible trends for further study of Eucommia ulmoides. Materials and methods: Information on Eucommia ulmoides was gathered via the internet (using Pub Med, Elsevier, Baidu Scholar, Google Scholar, Medline Plus, ACS, CNKI, and Web of Science) and from books in local libraries. Results: One-hundred twelve compounds of Eucommia ulmoides, including the main active constituents, lignans and iridoids, have been isolated and identified. In vitro and in vivo studies indicated that monomer compounds and extracts from Eucommia ulmoides possess wide-ranging pharmacological actions, especially in treating hypertension, hyperlipemia, diabetes, obesity, sexual dysfunction, osteoporosis, Alzheimer's disease, aging, lupus-like syndrome, and immunoregulation. Conclusions: Eucommia ulmoides has been used as a source of traditional medicine and as a beneficial health food. Phytochemical and pharmacological studies of Eucommia ulmoides have received much interest, and extracts and active compounds continue to be isolated and proven to exert various effects. Further toxicity and clinical studies are warranted to establish more detailed data on crude extracts and pure compounds, enabling more convenient preparations for patients. Therefore, this review on the ethnopharmacology, phytochemistry, biological activities, and toxicity of Eucommia ulmoides will provide helpful data for further studies as well as the commercial exploitation of this traditional medicine. [ABSTRACT FROM AUTHOR]

Background & Aims: Hirmi Valley liver disease was first reported in 2001 in Tigray, Ethiopia. 591 cases, including 228 deaths, were reported up to December 2009. The pyrrolizidine alkaloid acetyllycopsamine was detected in stored grain and residents reported adding the pesticide DDT (dichlorodiphenyldichloroethylene) directly to their food stores. We aimed to characterise the clinical features of the disease, and explore the role of these chemicals in its aetiology. Methods: 32 cases were examined and full clinical histories taken. Nine cases underwent liver biopsy in hospitals. Serum and urine samples were collected from cases and controls. Urine was analysed for acetyllycopsamine by UPLC-MS. Total DDT in serum was measured by ELISA. Hepatotoxicity of DDT and acetyllycopsamine alone or in combination was explored in C57BL/6J mice. Results: Clinical presentation included epigastric pain, abdominal swelling, bloody diarrhoea, hepatomegaly, splenomegaly, and ascites. Histology revealed acute injury characterised by centrilobular necrosis or chronic injury with bile ductular reaction, cytomegaly and fibrosis but no hepatic vein occlusion. Acetyllycopsamine was detected in urine samples taken in the affected area with significantly greater concentrations in 45 cases than in 43 controls (p =0.02). High levels of DDT (>125ppb) were detected in 78% of serum samples. In mice, DDT (3×75mg/kg) significantly increased the hepatotoxicity (plasma ALT, p =0.0065) of acetyllycopsamine (750mg/kg), and in combination induced liver pathology similar to Hirmi Valley liver disease including centrilobular necrosis and cytomegaly. Conclusions: This novel form of disease appears to be caused by co-exposure to acetyllycopsamine and DDT. [Copyright &y& Elsevier]

Background: Neonatal leukemoid reaction (NLR) is often accompanied by infectious or non-infectious diseases, a low birth weight, sepsis, prematurity, ventricular hemorrhage, and bronchial dysplasia. It has an incidence rate of 1.3-15% and a mortality rate of about 41.4%. Previous studies on NLR have largely focused on its pathogenesis and clinical cases, but little is known about its prognostic laboratory indicators. We found that some of the NLR exhibited obviously elevation in liver function tests like aspartate transaminase (AST) and lactate dehydrogenase (LDH) which were not took by all the LR infants. The necessity for liver function tests for the prognosis of NLR was still unclear., Methods: A total of 39 premature infants with NLR at the First Hospital of Jilin University between March 2016 and March 2017 were included in this retrospective cohort study. The infants were divided into death and cured group based on the clinical outcomes. Premature infants with LR and death were defined as the case group (n=14), while infants without death were defined as the control group (n=25). Confounding factors such as age and gender between the two groups were controlled. Blood routine tests, including the white blood cell (WBC) count and subtypes, and liver function, and clinical features were recorded and analyzed. T tests were used to examine the differences in the laboratory indicators between the NLR and control groups. Receiver operating characteristic curves (ROCs) and areas under the curve (AUCs) were used to examine laboratory indicators for prognosis., Results: For predicting clinical outcomes, the ROC curves showed that the cut-off values for AST and LDH were 279 and 1,412 U/L, respectively. The sensitivity and specificity for AST were 92% and 71.43%, respectively, with an AUC of 0.894, while the sensitivity and specificity for LDH were 88% and 78.57%, respectively, with an AUC of 0.911., Conclusions: This innovative study investigated the NLR prognosis depending on laboratory tests. We found that serum AST and LDH levels had reliable predictive value in determining adverse outcomes of NLR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-543/coif). The authors have no conflicts of interest to declare., (2022 Translational Pediatrics. All rights reserved.)

Abstract: The objective of this study was to develop and evaluate the antitumor activity and the safety of a delivery system containing mesoporous silica nanoparticles (MSN) coated with pH-responsive poly (N-isopropylacrylamide-co-methacrylic acid; P NIPAM-co-MAA) for doxorubicin (DOX) delivery (P-MSN-DOX) in vitro and in vivo. We reported that P-MSN-DOX nanoparticles (190±30nm) offered a DOX-loading coefficient of more than 20%. DOX release from the P-MSN-DOX formulation was pH-dependent with enhanced antitumor effects in vitro compared with traditional MSN-DOX, which was weakly cytotoxic due to negligible drug release at tested pHs. P-MSN-DOX circulated longer, with less cardiac and renal accumulation as shown by pharmacokinetics and biodistribution studies in vivo. Also, the P-MSN-DOX delivery system had greater antitumor activity in mice bearing a murine sarcoma S-180 cell line. This finding was correlated with both in vitro and in vivo. Subacute toxicity tests revealed a low P-MSN-DOX toxicity in vivo, as well. Thus, P-MSN-DOX appears to be an efficacious and safe cancer treatment strategy. [Copyright &y& Elsevier]