Alanine Aminotransferase Concentrations Research Articles

Cabozantinib monotherapy for advanced adrenocortical carcinoma: a single-arm, phase 2 trial

Adrenocortical carcinoma is a rare malignancy with poor response to systemic chemotherapy. Mitotane is the only approved therapy for adrenocortical carcinoma. Cabozantinib is a multikinase inhibitor approved in multiple malignancies. This is the first prospective trial to explore the anti-tumour activity, safety, and pharmacokinetic profile of cabozantinib in patients with advanced adrenocortical carcinoma. This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with advanced adrenocortical carcinoma was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients had histologically confirmed adrenocortical carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an estimated life expectancy of at least 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with adequate organ function. Patients who had used mitotane within 6 months of study participation were required to have a serum mitotane level of less than 2 mg/L. Patients were given oral cabozantinib 60 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was progression-free survival at 4 months, assessed in all patients who received at least one dose of study drug per protocol. This study is registered with ClinicalTrials.gov, NCT03370718, and is now complete. Between March 1, 2018, and May 31, 2021, we enrolled 18 patients (ten males and eight females), all of whom received at least one dose of study treatment. Of the 18 patients, eight (44%) had an ECOG performance status of 0, nine (50%) patients had a performance status of 1, and one (6%) patient had a performance status of 2. Median follow-up was 36·8 months (IQR 30·2-50·3). At 4 months, 13 (72·2%; 95% CI 46·5-90·3) of 18 patients had progression-free survival and median progression-free survival was 6 months (95% CI 4·3 to not reached). One patient remains on treatment. Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients. The most common grade 3 adverse events were lipase elevation (three [17%] of 18 patients), elevated γ-glutamyl transferase concentrations (two [11%] patients), elevated alanine aminotransferase concentrations (two [11%] patients), hypophosphatemia (two [11%] patients), and hypertension (two [11%] patients). One (6%) of 18 patients had grade 4 hypertension. No treatment related deaths occurred on study. Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing. Exelixis.

Anti-diabetic effect of <i>Eucalyptus camaldulensis</i> (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. 
 Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. 
 Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p < 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p < 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p < 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. 
 Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.

Effects of Clothianidin on Biochemical Parameters of Adult Zebrafish

The ubiquitous use of insecticides leads to detrimental effects on non-target organisms due to accidental exposure. Neonicotinoid insecticides are popularly used worldwide for their high affinity for arthropod nicotinic receptors which effectively kill insect pests. Low affinity towards vertebrate nicotinic receptors, make them safer as compared to traditional insecticides. Recent studies demonstrated that neonicotinoid exposure can cause some toxicity in vertebrates including humans. Zebrafish is one of the popular model organisms to study ecotoxicity. This is the first study on adult zebrafish to report the effect of novel neonicotinoid, Clothianidin on mortality, liver antioxidant stress profile, liver function profile and brain acetylcholinesterase (AChE). Observations were made over two treatment periods, 96 hours, and 21 days, in five groups exposed to varying concentrations of Clothianidin viz. 30mg/L, 50mg/L, 70mg/L, 90mg/L, 110mg/L and a control. Although no mortality was observed, Clothianidin exposure led to increased activity of superoxide dismutase (SOD) enzyme, lipid peroxidation and decreased catalase (CAT), glutathione-S-transferase (GST). Treated groups also showed increased concentrations of liver enzyme alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). These results indicate that Clothianidin causes disturbances in the hepatic function. A prominent decreasing trend observed in brain AChE shows that Clothianidin inhibits AChE in adult zebrafish. Further investigations on DNA damage and gene expression studies could be conducted to understand the exact mechanism of action of Clothianidin

Conch Shell (Turbinella pyrum) Powder: A Potential Marine Biological Source of Calcium and Some Trace Minerals for Growing Crossbred Calves.

The present study was conducted to evaluate the effect of feeding conch shell (Turbinella pyrum) powder (either fresh or calcined) as a marine organic source of calcium (Ca) supplemented in the diet of crossbred calves on voluntary intake, growth performance, and blood biochemistry in growing crossbred Jersey calves. A growth trial of 90days was conducted on 15 Jersey crossbred female calves (Av. weight, 70.68 ± 2.90kg; Av. age, 197.73 ± 12.40days), equally divided into three groups of 5 animals each, i.e., control (T0), treatment 1 (T1), and treatment 2 (T2). All animals were fed total mixed ration (TMR) prepared with a concentrate mixture, chaffed paddy straw, and green fodder at the ratio of 40:30:30 on DM basis. Calves under the control group were fed with TMR containing a standard mineral mixture having dicalcium phosphate (DCP) as a Ca source. Calves under T1 group were supplemented with TMR containing fresh conch shell powder (FCSP), and T2 calves were fed with TMR containing conch shell calcined powder (CSCP) as Ca source. We observed 11.66% increase (p < 0.01) in Ca concentration in CSCP compared to FCSP. The concentration of minerals like Mg, Co, Mn, and Fe was enhanced in CSCP compared to the FCSP. However, the calcination process of fresh conch shell powder (FCSP) reduced the concentration of Cu, and Zn. The Ca/P ratio was estimated as 2.11, 2.06, and 2.10 in T0, T1, and T2 diets, which could be considered ideal for calf ration. Calves under T1, and T2 groups consumed significantly (p < 0.001) greater amounts (g/kg W0.75) of DM and CP compared to T0. However, increased voluntary intake did not translate into increased body weight gain (kg), and feed conversion ratio (kg DMI/kg gain) in T1 and T2 groups in comparison to T0. We observed similar blood glucose, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transaminase (ALT) concentration among the three treatments. Ca, and P levels in blood plasma were also identical among the three groups. The digestibility of Ca was increased significantly (p = 0.01) in FCSP (T1)- and CSCP (T2)-treated calves compared to control (T0) calves. Similarly, T1 and T2 enhanced P digestibility compared to T0. This first report with short-term experimentation depicted some promising scope for the use of locally available conch shell powder (fresh or calcined form) as a potential source of Ca for feeding to livestock, because these new sources of Ca did not affect intake, digestibility of Ca and P, growth performance, blood chemistry, and liver enzymes negatively in weaned crossbred calves.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study

ObjectiveThe association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. MethodsPeople who had participated in health check-ups in 2006–2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). ResultsDuring 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01–1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01–1.13). Besides, the HR was 1.10 (95 % CI=1.06–1.15), 1.13 (95 % CI=1.08–1.18), and 1.22 (95 % CI=1.16–1.30) (P for trend <0.001) in (10–20], (20–30], and (30–40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. ConclusionPeople with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers.

Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2-15.1 mg/dL; 0.01-0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79-260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug-drug interactions leading to hepatotoxicity. Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

Biochemical Evaluation of Adansonia Digitata Methanolic Leaf and Stem Bark Extract on Streptozotocin Induced Diabetic Rats

Several herbal preparations are used to treat diabetes; however, their overall biochemical effects other than hypoglycemic effects are scanty. This study therefore was designed to evaluate the effect of methanolic extract of leaves and stem-bark of Adansonia digitata on biochemical indices of streptozotocin-induced diabetic rats. Sixty-three wistar rats were distributed into 9 groups of 7 each. The test animals were intraperitoneally administered with single dose of 50 mg/kg streptozotocin and monitored for 72 hours for development of hyperglycemia. Diabetic rats were treated in 12 h cycles for three weeks with 100 mg/kg, 200 mg/kg and 300 mg/kg of both leaves and stem-bark of Adansonia digitata methanolic extract and metformin (50 mg/kg). Non-diabetic control rats received a lacebo of distilled water. Group 1 served as normal control, group 2 served as diabetic control, while groups 4-9 were diabetic rats treated orally with methanolic leave and stem-bark extracts of Adansonia digitata (100 mg/kg, 200 mg/kg and 300 mg/kg) for 21days. Group 3 animals were diabetic rats treated with anti-diabetic drug (metformin 50 mg/kg). The levels of fasting blood sugar (FBS), electrolytes (Na+, K+, Cl-), Urea and creatinine Triglyceride (TG), Cholesterol  (CHOL), thiobarbituric acid reactive substance (TBARS), White Blood Cell (WBC) count, Red Blood Cell (RBC) count, Haemoglobin (HGB), Hematocrit (HCT), Platelet (PLT), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), Mean Cell Haemoglobin Concentration (MCHC), Lymphocyte (LYM), aspartatate aminotransfrease (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), catalase (CAT) and superoxide dismutase (SOD) activities total, total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentrations were assayed.  The results indicated that the concentrations of Na+, K+, Cl-, creatinine, urea TBARS, ALT, AST, ALB, CHOL and IB bilirubin were significantly (p&lt;0.05) increased, while the levels of WBC, RBC, HGB, HCT, PLT, LYM, MCV SOD and CAT were reduced in the diabetic control (p&lt;0.05). The Adansonia digitata methanolic leaves and stem-bark extract significantly increased WBC, RBC, HGB, HCT, PLT, MCV, LYM, TP, CAT and SOD activity and reduced the FBS, Na+, K+, Cl-, TBARS, ALT, AST, creatinine, urea and bilirubin concentrations significantly (p&lt;0.05) compared to normal control. However, treatment with metformin showed slight modification in the changes observed compared to Adansonia digitata methanolic leaves and stem-bark extract. MCV and MCHC reduced non-significantly (p&gt;0.05) in the diabetic animals as compared to the normal control and the extract-treated rats, while they increased non- significantly (p&gt;0.05) in the test groups when compared to the diabetic control.  Levels of TB, DB, and TG showed non-significant (p&lt;0.05) increase in diabetic control, but treatment with extracts and metformin caused non-significant decrease (p&lt;0.05). Diabetic control exhibited significantly (p&lt;0.05) decreased ALB levels and non-significant TP decrease compared to normal control, while Adansonia digitata extracts and metformin significantly increased ALB and non-significantly increased TP levels compared to diabetic control. The study concluded that Adansonia digitata extracts reversed diabetes-induced oxidative stress in rat hepatocytes, potentially through beta cell regeneration or insulin release stimulation, suggesting their potential for managing diabetic complications.

The effects of astaxanthin supplementation on liver enzymes levels.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview.

Autoimmune hepatitis is an immune-mediated inflammatory condition of the liver of undetermined cause that affects both sexes, all ages, races, and ethnicities. Its clinical presentation can be very broad, from having an asymptomatic and silent course to presenting as acute hepatitis, cirrhosis, and acute liver failure potentially requiring liver transplantation. The diagnosis is based on histological abnormalities (interface hepatitis), characteristic clinical and laboratory findings (increased aspartate aminotransferase, alanine aminotransferase, and serum IgG concentration), and the presence of one or more characteristic autoantibodies. The large heterogeneity of these clinical, biochemical, and histological findings can sometimes make a timely and proper diagnosis a difficult task. Treatment seeks to achieve remission of the disease and prevent further progression of liver disease. First-line therapy includes high-dose corticosteroids, which are later tapered to decrease side effects, and azathioprine. In the presence of azathioprine intolerance or a poor response to the standard of care, second-line therapy needs to be considered, including mycophenolate mofetil. AIH remains a diagnostic and therapeutic challenge, and a further understanding of the pathophysiological pathways of the disease and the implementation of randomized controlled trials are needed.

Activity and safety of eltrombopag in combination with cyclosporin A as first‑line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study

Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200-400 μg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with ClinicalTrials.gov, NCT02998645, and has been completed. 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33-60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. Novartis Pharmaceuticals.

Toxic effects of clindamycin-hydrochloride in healthy rodents

Background: Systemic administration of clindamycin-hydrochloride (an antibiotic) is mainly associated with gastro-intestinal disturbances and allergic reactions. Little is known of its haematological and biochemical toxicity.&#x0D; Objective: To evaluate the haematological and biochemical changes associated with indiscriminate administration of oral clindamycin-hydrochloride in clinically healthy rodents.&#x0D; Materials and Methods: Twenty Wistar rats (130-189 grams) divided into four groups (A-D) of five rats each were used. Rats in group A (control) were treated with distilled water. Groups B-D received 0.2mL (below normal dose), 0.4mL (normal dose) and 1.0mL (above normal dose) of clindamycin-hydrochloride (75mg/5mL) at 8 hourly intervals, three times daily for 14 days, respectively. Thereafter, blood was collected through both ocular and cardiac puncture into ethylene diamine tetra acetic acid (EDTA) and lithium heparin bottles for evaluation of haematological and biochemical parameters, respectively.&#x0D; Results: Significant (P &lt; 0.05) increases in total white blood cell (WBC) counts and decreases in eosinophil (Eos) counts occurred in clindamycin-treated rats. In addition, significant (P &lt; 0.05) increases in concentrations of Total cholesterol, Triglyceride and High-density lipoprotein, respectively, as well as decreases in concentrations of Albumin, Alanine transaminase and Gamma-glutamyl transpeptidase, respectively also occurred in clindamycin-treated rats.&#x0D; Conclusion: Indiscriminate use of clindamycin-hydrochloride produces adverse haematological and biochemical changes in Wistar rats which may be a reflection of systemic toxicity, allergic reaction as well as liver and kidney dysfunction.

Effect of dietary methionine hydroxy analogue‐free acid (MHA‐FA) supplementation levels on growth performance, blood metabolites and immune responses in broiler chickens

AbstractBackgroundBroiler diets are commonly supplemented by liquid methionine hydroxy analogue‐free acid (MHA‐FA) containing as product with 88% of active substance to meet sulphur amino acid (SAA) requirements.ObjectivesTwo experiments were conducted to assess the effects of different dietary MHA‐FA levels on growth performance, blood metabolites and immune responses in broilers.MethodsIn experiments 1 and 2, 432 and 360 male broilers were fed either a basal corn–soya bean meal diet that met the energy and nutrient requirements with the exception of SAAs or the basal diet supplemented with 5 graded levels of MHA‐FA (+0.9 and +0.8 g/kg), for 1–11 and 11–24‐day ages, respectively. Chicks were vaccinated with inactivated H9N2/Newcastle disease (ND) and live‐ND on days 5 and 11, respectively.ResultsResponses in both experiments had similar tendency at corresponding dietary MHA‐FA levels. By increasing dietary MHA‐FA level, weight gain (WG), feed efficiency (FE), relative breast weight (RBW) and immunity against ND and avian influenza virus inoculation improved with quadratic trend. Blood serum triglyceride, low‐density lipoprotein, alanine aminotransferase and alkaline phosphatase concentration were affected in response to dietary MHA‐FA levels with quadratic trends. By using broken‐line regression analysis, the optimum dietary MHA‐FA levels for optimized WG, FE and RBW during 1–10‐day age were obtained at 2.20, 3.31 and 3.33 g/kg, respectively; based on MHA‐FA content of Met equivalent, the digestible SAA requirements were estimated 0.81%, 0.91% and 0.92%, respectively. Similarly, for the 11–24‐day age period, the optimum dietary MHA‐FA supplementation levels were obtained 1.79, 2.21, 2.41 and 2.53 g/kg, with the digestible SAA requirements estimated 0.75%, 0.79%, 0.80% and 0.81% for optimized WG, FE, RBW and immune responses, respectively.ConclusionsSupplemental levels of MHA‐FA that optimize performance, breast meat and immunity in broilers fed corn–soya bean meal diet, varied from 0.18% to 0.33%, correspond to age and what traits are considered for optimization.

Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.

Activity of enzymes in the follicular fluid and outcome of in vitro fertilization.

Defining certain parameters of the oocyte microenvironment that can be simply and quickly detected and that enable differentiation of oocytes that have better or worse quality could potentially increase the efficacy of the in vitro fertilization (IVF) method. Follicular fluid represents the microenvironment for the development of oocytes during different stages of maturation. Enzymes present in the follicular fluid may affect the quality of oocytes. There are inconsistencies in the literature concerning enzyme concentration in follicular fluid. The main aim of this study was to examine whether the concentration of enzymes aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and lactate dehydrogenase in follicular fluid can influence the outcome of IVF. The study included 120 patients who were involved in the process of IVF. We used the follicular fluid obtained after follicular aspiration in the ovaries as biological material for the analysis. The values of enzymes LDL (method-kinetic UV test), aspartate aminotransferase (method-kinetic UV test), ALT (method-kinetic UV test) and alkaline phosphatase (method-colorimetric kinetic test) in the follicular fluid were determined on the analyzer АU 680, Becman Coulter. The criteria of the Istanbul consensus of clinical embryologists were used for the embryo assessment. The software package SPSS 20 was used for the statistical processing of data. The results of follicular fluid sample analysis showed a correlation between ALT concentration in the follicular fluid and IVF outcome. Based on our results, we can conclude that ALT concentration affects the outcome of IVF.

Indexing serum and mucous biochemical parameters of endangered Chinese sturgeon Acipenser sinensis with implications for health assessment.

The Chinese sturgeon (Acipenser sinensis) is a critically endangered aquatic fish. Health monitoring and welfare assessments are critical for the conservation of Chinese sturgeon. In this study, biochemical parameters of serum and skin mucus in Chinese sturgeon were examined to evaluate the potential biomarkers. Serum and mucous samples were obtained from Chinese sturgeon, and the levels of total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), lactic acid (LD), acid phosphatase (ACP), lysozyme (LYZ), glucose (GLU), and cortisol were determined. The concentrations of ALT, AST, cortisol, and LYZ were significantly higher in the mucous group than those in the serum group (p < 0.05). In addition, the concentrations of ALP, ACP, LD, LDH, CK, and TP were significantly higher level in the serum group than those in the mucous group (p < 0.05). Moreover, the correlations between serum and mucous biochemical parameters were established. Statistical analysis showed a positive correlation between serum and skin mucous markers (ACP, cortisol, and LYZ). AST versus ALT in serum and mucus showed a significant positive correlation (p < 0.01). A significant positive correlation was found between cortisol and CK in mucus (p < 0.01). Moreover, LD versus LDH in serum showed a significant but weak positive correlation (p < 0.01). Principal component analysis revealed a complete separation between the serum and mucous groups, with the biomarkers that contributed the most being ALP, TP, ALT, and AST. This study provides baseline data and reference intervals for serum and mucous biochemical parameters in presumably healthy Chinese sturgeons. The current study has important implications for the development of conservation strategies and the conservation status of critically endangered species.

Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization.

Observational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications. Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses. UVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications. Robust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention.

The Effect of Yucca schidigera Extract on Serum Metabolites of Angus Crossbreed Steers with Metabolomics.

This study was conducted to explore the potential effect of Yucca schidigera extract (YSE) on the metabolism of beef cattle. Thirty Angus crossbreed steers were selected, with an initial mean body weight of 506.6 ± 33.3 kg, and assigned to two treatments: a diet with no additives (CON group) and a diet supplemented with 1.75 g/kg of YSE (YSE group) (on a dry matter basis). The experiment lasted for 104 days, with 14 days for adaptation. The results showed that adding YSE could significantly improve the average daily gain (ADG) from 1 to 59 d (15.38%) (p = 0.01) and 1 to 90 d (11.38%) (p < 0.01), as well as dry matter digestibility (DMD) (0.84%) (p < 0.05). The contents of alanine aminotransferase, aspartate aminotransferase, and bilirubin and the total antioxidant capacity were increased and blood urea was reduced in the YSE group, compared to the CON group (p < 0.05). Both the glycerophospholipids and bile acids, including phosphocholine, glycerophosphocholine, PC(15:0/18:2(9Z,12Z)), PE(18:0/20:3(5Z,8Z,11Z)), PE(18:3(6Z,9Z,12Z)/P-18:0), LysoPC(15:0), LysoPC(17:0), LysoPC(18:0), LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), deoxycholic acid, glycocholic acid, and cholic acid, were upregulated by the addition of YSE. In summary, YSE may improve the ADG by increasing the blood total antioxidant capacity and glycerophospholipid synthesis, maintaining steers under a healthy status that is beneficial for growth. Furthermore, YSE may also increase the expression of bile acid synthesis, thereby promoting DMD, which, in turn, offers more nutrients available for growth.

Curcumin supplementation effect on liver enzymes in patients with nonalcoholic fatty liver disease: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

Clinical evidence from investigations of the effects of curcumin on liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD) have led to inconsistent results. The aim of this systematic review and meta-analysis was to investigate the overall effects of curcumin and curcumin plus piperine supplementation on liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) in patients with NAFLD. The Scopus, Web of Science, PubMed, and Cochrane Library databases were searched from inception through July 2023, using search terms representing NAFLD and liver enzymes. Articles were screened independently by 2 researchers based on PICOS inclusion criteria. The following data were extracted: first author's name, study location, year of publication, mean age, study duration, study design, participants' sex, number of participants in each group, dose of curcumin supplementation, and ALT, ALP, and AST concentrations. Risk of bias was assessed using the Cochrane Collaboration's modified risk-of-bias tool. Fixed- or random-effects meta-analysis was performed to estimate the effects of curcumin on liver enzymes, considering heterogeneity across studies. The I2 and Cochran's Q tests were used to assess heterogeneity between studies. Overall, 15 randomized controlled trials comprising 905 participants were eligible for this meta-analysis. Curcumin supplementation significantly reduced ALT (weighted mean difference [WMD], -4.10, 95%CI, -7.16 to -1.04) and AST (WMD, -3.27; 95%CI, -5.16 to -1.39), but not ALP (WMD, -0.49; 95%CI, -1.79 to 0.82). Curcumin plus piperine supplementation had no significant effect on ALT (WMD, -3.79; 95%CI, -13.30 to 5.72), and AST (WMD, -1.1; 95%CI, -3.32 to 1.09). Curcumin supplementation improved AST and ALT levels compared with the control group. However, better-designed randomized controlled trials with larger sample sizes and of higher quality are needed to assess the effects of curcumin on ALP. PROSPERO registration no. CRD42023448231.

Features of metabolism in chronic wound remodelling

Background/Aim: The treatment of chronic wounds continues to be a pressing problem throughout the world. Healing occurs through some evolutionarily conserved biochemical pathways. The mechanisms of development of disorders of reparative regeneration are not fully understood. The work aimed to study the dynamics of changes in metabolic parameters during the healing of chronic wounds. Methods: Healthy Wistar rats were divided into two groups. The animals of the first group were intact. Chronic wounds were simulated for the animals of the second group. On days 7, 14 and 28 after wound creation, the animals were euthanised. Biochemical parameters such as glucose, total protein, albumin, cholesterol, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were assessed in the blood serum of animals. Results: It was found that the maximum decrease in glucose and total protein levels in the blood serum of animals in the experimental groups compared to intact animals was observed 2 weeks after surgery: the glucose concentration in rats was 1.7 times lower (p &lt; 0.001). The level of albumin in the blood serum of experimental animals compared to intact animals was reduced by 1.5 times after 14 days (p &lt; 0.001) and by 1.2 times after 28 days (p &lt; 0.01). A week after surgery, the concentration of urea in the blood serum of experimental animals was 1.3 times higher (p &lt; 0.01) than in intact rats and by day 28 after surgery, the urea level was 1.4 times higher (p &lt; 0.001). The reduction in cholesterol and creatinine levels was not significant. An increase in AST, AST and ALP levels in the blood serum of experimental animals was shown. An increase in the blood serum of animals 7 days after surgery compared to the indicators of intact animals: ALP concentrations by 2.8 times (p &lt; 0.001) and ALT concentrations by 1.4 times (p &lt; 0.001) was established. The AST level significantly increased 14 days after surgery (p &lt; 0.05). Conclusions: The study of metabolic parameters allows monitoring of the state of the body during the healing process of wounds to correct treatment tactics.

Evaluation of the safety and immune stimulatory effects of multi-strain Lab Mix product on laboratory animals

Background & aimsProbiotics are alive and beneficial bacteria used as food complements with sufficient amounts to improve and balance the intestinal flora in the human gastrointestinal tract and inhibit harmful microorganisms. In this study, we conducted experiments to evaluate he safety and the effect of one of our probiotics on selected biochemical parameters in animal models. MethodsLabMix is a probiotic product containing three bacterial strains, including Lactobacillus acidophilus LA 304.17, Lactobacillus casei LC 304.08, and Bifidobacterium bifidum BF 304.98, with a density of 9 × 109 CFU/g and being mixed with suitable excipients. In this study, we conducted experiments to evaluate LabMix's acute ttoxicity in mice as well as subchronic toxicity in rats. ResultsThe LD50 dose in mice of this product could not be determined since no death or disorder was recorded. In rats receiving LabMix with doses of 2.52 × 109 CFU/kg and 12.6 × 109 CFU/kg continuously for 28 days, this product caused no significant changes in the amount of red and white blood cells and platelets. Similarly, no significant changes were recorded in serum concentrations of hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, protein, cholesterol, bilirubin, and creatinine. Besides, LabMix products also did not cause any changes in the histology of the liver, kidney, and spleen in rats. Moreover, LabMix was well tolerated without affecting the normal growth and feeding of rats. Furthermore, LabMix also decreased serum cytokines and increased serum and gut mucosal IgA antibodies. ConclusionsLabMix product is possibly considered safe for human., and this sproduct reduced the release of pro-inflammatory cytokines (IL-6 and TNF-α), but increased IgA levels. However, it is necessary to further evaluate the product's effectiveness in the preclinical phase as well as in further phases before mass production and commercialization.