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Introduction: Chronic exposure to pesticides causes various adverse health effects, mainly at a neurological level. However, there is little evidence focused on liver tissue injury and transaminase activity as indicators of effect. Methods: A cross-sectional study was designed based on medical-occupational records of workers from an agro-export company in Peru to associate the levels of butyrylcholinesterase (BChE) transaminases (ALT and AST). Occupational medical records were reviewed to obtain demographic and occupational information and laboratory values of BChE activity and transaminases. Results: We evaluated 459 records, and 69.9% were men. The mean age was 34.9 ± 11.5 years. BChE, ALT, and AST levels were 6238.8 ± 709.1 U/l, 34.4 ± 12.5 U/l, and 22.4 ± 8.5 U/l, respectively. The proportion of inhibited BCHE and elevated transaminase levels was 15.3% and 21.6%, respectively. We found a significant association between BChE inhibition and elevation of transaminases (AST: PR = 0.798, 95%CI: 0.716–0.889; ALT: PR = 0.419, 95%CI: 0.239–0.736). Conclusion: The potential usefulness of transaminases is shown as a biomarker of exposure and monitoring in occupational health programs for the agro-industry. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is highly consequential to global health among chronic diseases. Due to a limited researches that have examined relationships between liver enzymes and DM, this study aimed to investigate the link between elevated liver enzymes and diabetes among Prospective Epidemiological Research Studies in Iran (PERSIAN) Guilan cohort study (PGCS) population. Methods: This cross-sectional study was conducted on 10519 individuals. The demographic and clinical information of the participants was recorded. The changes in alanine aminotransferases (ALT) and aspartate aminotransferases (AST), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were evaluated. IBM SPSS Version 21 was used to analyze the data, with a significance level < 0.05. Results: The frequency of diabetes was 24.1% and was more prevalent in women than men (27.4% vs. 20.2%, p< 0.001). After removing all confederates, patients with elevated ALT, AST, GGT, and ALP levels were 1.27, 1.27, 1.52, and 1.46 times more likely to have diabetes, respectively. The likelihood of developing diabetes rose in correlation with the number of elevated liver enzymes, up to almost 1.77-fold among subjects with three or four increased liver enzymes. Conclusion: Patients diagnosed with diabetes exhibited significantly increased levels of liver enzymes compared to those without diabetes. Also, impairment of three or four liver enzymes demonstrated a positive correlation with an elevated likelihood of DM. This indicates the importance of considering the liver status in the management of the DM population. [ABSTRACT FROM AUTHOR]

Gan-Jiang-Ling-Zhu (GJLZ) decoction, a classical Chinese herbal prescription, can be applied for the treatment of metabolic diseases including liver steatosis. Although GJLZ decoction has been widely applied clinically for thousands of years, the mechanism of GJLZ decoction behind treatment of nonalcoholic steatohepatitis (NASH) remains relatively unelucidated. To elucidate the efficacy of GJLZ decoction in the treatment of NASH and to investigate its underlying mechanisms from an epigenetic perspective. The quality control of chemical components in GJLZ decoction was conducted. C57BL/6J mice with NASH were induced by feeding them a choline-deficient-high-fat-diet (CDHFD), along with GJLZ decoction intervention for 4 weeks. Then NASH phenotypes including histological steatosis, inflammation, hepatic apoptosis, fibrosis, serum liver enzyme and lipid level were measured. N6-methyladenosine (m6A) and transcriptome sequencing were performed. Levels and functions of methyltransferases and different genes were performed by quantitative polymerase chain reaction, immunofluorescence, gene knockdown, oil red O staining and western blotting. GJLZ decoction significantly reduced liver weight, liver index and improved hepatic steatosis, and inflammation, as well as inhibited hepatic apoptosis and fibrosis. Moreover, GJLZ decoction significantly reduced the levels of lactate dehydrogenase, aminotransferase, triglyceride, aspartate aminotransferase, and inhibited levels of interleukin 6 and tumor necrosis factor α. Transcriptome and m6A sequencing revealed the landscape of transcriptome and m6A modification influenced by NASH and the following GJLZ decoction intervention. Eleven differential genes were identified, and GJLZ markedly promoted m6A level of UDP glucuronosyltransferase family 2 member A3 (Ugt2a3), to promote its expression. Additionally, GJLZ significantly promoted methyltransferase 14 (METTL14) expression, whereas METTL14 knockdown aggravated hepatocellular steatosis. Finally, METTL14 knockdown significantly reduced the level of Ugt2a3 by promoting its degradation, whereas, Ugt2a3 overexpression could markedly inhibit hepatocellular steatosis. GJLZ decoction demonstrates potential in alleviating CDHFD-induced NASH by modulating the METTL14-m6A-Ugt2a3 axis, offering a novel therapeutic approach for NASH treatment. [Display omitted] • GJLZ decoction significantly ameliorates hepatic inflammation and steatosis in CDHFD-induced mice. • GJLZ decoction significantly increased m6A level of Ugt2a3, to promote Ugt2a3 expression. • Knockdown of METTL14 aggravated hepatocellular steatosis and decreased Ugt2a3 expression by promoting its degradation. • GJLZ decoction alleviated CDHFD-induced NASH by modulating the METTL14-m6A-Ugt2a3 axis. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the role of Liver Stiffness Measurement (LSM) and serum transaminase levels for predicting early allograft failure (EAF) after liver transplantation (LT).A total of 189 patients who underwent LT were prospectively recruited in the study. Of these patients, 13 cases died or received re-transplantation within 90 days after surgery were classified as EAF group, while rest 176 patients were included in the non-EAF group. LSM values and serum transaminase levels within 1 week after operation were recorded and compared between two groups. The area under the curve (AUC) was utilized to assess the performance of LSM, serum transaminase and their combination in predicting EAF.The earliest significant difference in LSM between EAF and non-EAF group was observed on postoperative day 3 (POD-3) (p = 0.046). Comparing to non-EAF group, patients in the EAF group had higher aspartate-aminotransferase (AST) and alanine aminotransferase (ALT) on postoperative day 2 (POD-2)(p = 0.009, 0.033), and also demonstrated higher AST on POD-3 (p = 0.021). Furthermore, the reduction rate of AST/ALT from day 1 to day 3 (AST/ALT Red) were slower (p = 0.001, 0.014) in EAF group. Using a LSM value > 12.1 kPa and an AST level > 339U/L on POD-3 predicted EAF with a sensitivity of 89%, a specificity of 86%, and an AUC of 0.926, surpassing the traditional early allograft dysfunction (EAD) model.The combination of LSM values and AST levels on the third day after LT can effectively predict EAF and facilitate timely interventions.Methods: The objective of this study was to evaluate the role of Liver Stiffness Measurement (LSM) and serum transaminase levels for predicting early allograft failure (EAF) after liver transplantation (LT).A total of 189 patients who underwent LT were prospectively recruited in the study. Of these patients, 13 cases died or received re-transplantation within 90 days after surgery were classified as EAF group, while rest 176 patients were included in the non-EAF group. LSM values and serum transaminase levels within 1 week after operation were recorded and compared between two groups. The area under the curve (AUC) was utilized to assess the performance of LSM, serum transaminase and their combination in predicting EAF.The earliest significant difference in LSM between EAF and non-EAF group was observed on postoperative day 3 (POD-3) (p = 0.046). Comparing to non-EAF group, patients in the EAF group had higher aspartate-aminotransferase (AST) and alanine aminotransferase (ALT) on postoperative day 2 (POD-2)(p = 0.009, 0.033), and also demonstrated higher AST on POD-3 (p = 0.021). Furthermore, the reduction rate of AST/ALT from day 1 to day 3 (AST/ALT Red) were slower (p = 0.001, 0.014) in EAF group. Using a LSM value > 12.1 kPa and an AST level > 339U/L on POD-3 predicted EAF with a sensitivity of 89%, a specificity of 86%, and an AUC of 0.926, surpassing the traditional early allograft dysfunction (EAD) model.The combination of LSM values and AST levels on the third day after LT can effectively predict EAF and facilitate timely interventions.Results: The objective of this study was to evaluate the role of Liver Stiffness Measurement (LSM) and serum transaminase levels for predicting early allograft failure (EAF) after liver transplantation (LT).A total of 189 patients who underwent LT were prospectively recruited in the study. Of these patients, 13 cases died or received re-transplantation within 90 days after surgery were classified as EAF group, while rest 176 patients were included in the non-EAF group. LSM values and serum transaminase levels within 1 week after operation were recorded and compared between two groups. The area under the curve (AUC) was utilized to assess the performance of LSM, serum transaminase and their combination in predicting EAF.The earliest significant difference in LSM between EAF and non-EAF group was observed on postoperative day 3 (POD-3) (p = 0.046). Comparing to non-EAF group, patients in the EAF group had higher aspartate-aminotransferase (AST) and alanine aminotransferase (ALT) on postoperative day 2 (POD-2)(p = 0.009, 0.033), and also demonstrated higher AST on POD-3 (p = 0.021). Furthermore, the reduction rate of AST/ALT from day 1 to day 3 (AST/ALT Red) were slower (p = 0.001, 0.014) in EAF group. Using a LSM value > 12.1 kPa and an AST level > 339U/L on POD-3 predicted EAF with a sensitivity of 89%, a specificity of 86%, and an AUC of 0.926, surpassing the traditional early allograft dysfunction (EAD) model.The combination of LSM values and AST levels on the third day after LT can effectively predict EAF and facilitate timely interventions.Conclusions: The objective of this study was to evaluate the role of Liver Stiffness Measurement (LSM) and serum transaminase levels for predicting early allograft failure (EAF) after liver transplantation (LT).A total of 189 patients who underwent LT were prospectively recruited in the study. Of these patients, 13 cases died or received re-transplantation within 90 days after surgery were classified as EAF group, while rest 176 patients were included in the non-EAF group. LSM values and serum transaminase levels within 1 week after operation were recorded and compared between two groups. The area under the curve (AUC) was utilized to assess the performance of LSM, serum transaminase and their combination in predicting EAF.The earliest significant difference in LSM between EAF and non-EAF group was observed on postoperative day 3 (POD-3) (p = 0.046). Comparing to non-EAF group, patients in the EAF group had higher aspartate-aminotransferase (AST) and alanine aminotransferase (ALT) on postoperative day 2 (POD-2)(p = 0.009, 0.033), and also demonstrated higher AST on POD-3 (p = 0.021). Furthermore, the reduction rate of AST/ALT from day 1 to day 3 (AST/ALT Red) were slower (p = 0.001, 0.014) in EAF group. Using a LSM value > 12.1 kPa and an AST level > 339U/L on POD-3 predicted EAF with a sensitivity of 89%, a specificity of 86%, and an AUC of 0.926, surpassing the traditional early allograft dysfunction (EAD) model.The combination of LSM values and AST levels on the third day after LT can effectively predict EAF and facilitate timely interventions. [ABSTRACT FROM AUTHOR]

Pyridoxal-5′-phosphate (PLP)-dependent transaminases are key enzymes of amino acid metabolism in cells and remarkable biocatalysts of stereoselective amination for process chemistry applications. As cofactor-dependent enzymes, transaminases are prone to cofactor leakage. Here we discuss the holoenzyme-apoenzyme interconversion and the kinetics of PLP incorporation into the apo form of a PLP-dependent transaminase from Haliscomenobacter hydrossis. PLP binding to the apoenzyme was slow in buffer, but was accelerated in the presence of substrates. Two crystal structures of the apoenzyme were obtained: the directly obtained apoenzyme (PDB ID: 7P8O) and the one obtained by soaking crystals of the holoenzyme in a phenylhydrazine solution (PDB ID: 8YRU). The mechanism of PLP association with the apoenzyme was proposed on the basis of structural analysis of these apo forms. Three rearrangement steps, including (I) anchoring of the PLP via the phosphate group, (II) displacement of two loops, and (III) Schiff-bonding between the PLP and the ε-amino group of the catalytic lysine residue, reconstituted the active holo form of the transaminase from H. hydrossis. The results obtained allowed us to determine in the active site a permanent part and elements that are assembled by PLP, these findings may be useful for transaminase engineering for biocatalysis. [Display omitted] • PLP-dependent D-amino acid transaminase from Haliscomenobacter hydrossis is studied. • PLP incorporation into the apoenzyme occurs in three steps. • Two crystal structures of the apoenzyme under different conditions are obtained. • The catalytic loop shifts to an adjacent subunit upon cofactor release. • PLP binding to the apoenzyme is accelerated in the presence of substrates. [ABSTRACT FROM AUTHOR]