FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

MECHANISM OF SARS-COV-2 INVASION INTO THE LIVER AND HEPATIC INJURY IN PATIENTS WITH COVID-19

A large number of studies have shown that patients with Coronavirus disease 2019 (COVID-19) have different degrees of liver injury. However, the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion into the liver are still not fully understood. This review mainly summarizes the recently published works on the abnormal liver biochemical indicators and the mechanism of viral invasion with liver injury in COVID-19 patients. Generally, SARS-CoV-2 infection of the liver was caused by blood circulation or retrograde infection of digestive tract, which led to the liver injury through direct cytopathic effect induced by virus or immunopathological effect caused by excessive inflammation. Besides these, hypoxia, endothelial injury and drug-induced jury were also the main reasons of liver injury in COVID-19 patients. In the liver function indicators, elevated alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase levels with reduced albumin levels were observed in COVID-19 patients.

Method for diagnosing non-alcoholic liver steatosis

Purpose of the study. Development of a non-invasive method for the diagnosis of non-alcoholic hepatic steatosis.Material and methods. The study involved 21 patients with confrmed non-alcoholic hepatic steatosis on ultrasound examination with an average age of 42.1 ± 10.1 years. The control group consisted of 10 apparently healthy individuals. The following indicators were determined: body mass index (BMI), the level of gamma-glutamyl transpeptidase (GGTP), vasculoendothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum, and the steatosis index (IS) was calculated using the formula IS = –1.2390 + 0.0575 × BMI + 0.0064 × GGTP +0.0006 × VEGF + 0.0001 × IL-6. The index of the presence of hepatic steatosis according to liver ultrasound data was used as a dependent variable.Results. According to the examination results, BMI and serum concentrations of GGTP, VEGF, and IL-6 in patients with steatosis were signifcantly higher than in the control group (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively), which indicates the presence of cholestasis syndrome, signs of inflammation and endothelial dysfunction. The correlation coeffcient between BMI and the presence of non-alcoholic hepatic steatosis was 0.9; between GGTP and the presence of steatosis was 0.80; between VEGF and the presence of steatosis was 0.85; between IL-6 and the presence of steatosis was 0.80. The predictive value of each parameter of the model was assessed using a scale of values of the area under the ROC-curve (AUC). The model is effective (multiple correlation coeffcient R = 0.809; the share of the influence of the sum of the factors included in the model is R2 • 100 = 65.5%), statistically signifcant (criterion F = 12.318; p < 0.0001) and has excellent diagnostic characteristics.Conclusion. The proposed non-invasive method makes it possible to diagnose hepatic steatosis with a sensitivity of 95.2% and a specifcity of 97.0%: with IS equal to 0.5 or more, the presence of non-alcoholic hepatic steatosis is diagnosed, with IS less than 0.5 is not.

Rotating night shift work, sleep duration and elevated gamma-glutamyl transpeptidase among steelworkers: cross-sectional analyses from a Chinese occupational cohort

ObjectivesThis study aimed to evaluate the separate and combined effects of rotating night shift work and lifestyle factors with elevated gamma-glutamyl transpeptidase (GGT) among steelworkers.Design, setting and participantsThis cross-sectional study used the baseline information from a Chinese occupational cohort. The in-service workers of the production department of Tangsteel Company who participated in the occupational health examination in Tangshan from February to June 2017 were selected as the research objects.Main outcome measuresThe separate and combined effects of rotating night shift work and lifestyle factors with elevated GGT among steelworkers.ResultsThe information of 7031 subjects from the production department of Tangsteel Company was analysed. Results showed that the current shift workers and the workers with the duration of night shifts>19 years, the cumulative number of night shifts>1774 nights, the average frequency of night shifts≤7 nights/month and the average frequency of night shifts>7 nights/month had elevated odds of elevated GGT, compared with those who never worked night shifts, and ORs, (95% CIs) were 1.39, (1.10 to 1.75), 1.46, (1.15 to 1.86), 1.46, (1.15 to 1.85), 1.34, (1.04 to 1.73) and 1.37, (1.09 to 1.74) after adjustment for potential confounders. The independent effect of shorter sleep duration (<7 hours/day) on elevated GGT was not statistically significant. Among workers who had shorter sleep duration, the association between rotating night shift work and elevated GGT was statistically significant, but no associations were found among workers with the sleep duration of ≥7 hours/day. In addition, other lifestyle factors affected the association between rotating night shift work and elevated GGT.ConclusionsRotating night shift work is associated with elevated GGT among steelworkers. In particular, the effect of rotating night shift work on elevated GGT was affected by sleep duration and other lifestyle factors.

Serum FGF21 levels are altered by various factors including lifestyle behaviors in male subjects

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Factors related to the spontaneous passage of common bile duct stones through the papilla: a single-center retrospective cohort study

Objective Common bile duct (CBD) stones can spontaneously pass through the papilla. This study explored factors associated with stone passage by comparing differences in the clinical features of stones retained in the CBD and excreted stones. Methods Data were retrospectively collected for all patients who were hospitalized in our center between March 2016 and May 2021 with clinical, laboratory, or imaging evidence of CBD stones. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and were classified into two groups: group A (stones extracted by ERCP, n = 86) and group B (stones discharged before ERCP, n = 15). Demographic data, biochemical and radiological findings were compared between the groups. Results Stone size (0.82 vs. 0.33 cm), and levels of total bilirubin (58.2 vs. 28.8 μmol/L), gamma-glutamyl transpeptidase (416.7 vs. 193.9 U/L), alkaline phosphatase (191.9 vs. 123.1 U/L), carbohydrate antigen 19-9 (603.7 vs. 37.2 U/mL), and α-L-fucosidase (37.4 vs. 22.6 U/L) were significantly higher in group A than in group B. Logistic regression analyses showed that stone size was the only factor significantly associated with spontaneous passage of CBD stones. Conclusions CBD stones less than 0.33 cm in size may be self-expelled through the papilla.

A Case Report of Alcoholic Liver Disease with Jaundice Treated with Korean Medicine

Objective: This study aimed to report a case of alcoholic liver disease with jaundice that was improved with Korean medicine treatment.Methods: A patient who developed jaundice due to continuous drinking was treated with herbal medicine, acupuncture, moxibustion, and cupping. Blood tests were performed to measure the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GTP), total bilirubin, albumin, and total protein; AST/ALT ratio; and mean corpuscular volume (MCV). Jaundice parameters were subjectively recorded at 3-day intervals.Results: After treatment, the AST, ALT, ALP, γ-GTP, and total bilirubin levels; MCV; and jaundice were decreased.Conclusion: Korean medicine treatment appeared to be an effective method for alcoholic liver disease with jaundice.

Diagnostic capabilities of the biochemical composition of amniotic fluid in assessing fetal conditions

Aim. To analyze the nature of changes in the biochemical parameters of amniotic fluid during fetal hypoxia. Methods. The study was carried out in the maternity ward of the Republican Clinical Hospital named after Kuvatov (Ufa) between January 2016 and September 2018. The main group 72 women in labor with symptoms of fetal distress, the control group 70 women in labor without it. The biochemical composition of the amniotic fluid was measured using an analyzer. Statistical analysis was performed by using the Statistica 10.0 software. Comparison of qualitative characteristics was carried out by using Fisher's exact test when comparing quantitative data, the MannWhitney test. The statistical significance of the differences was set at p 0.05. Results. It was found that in fetal distress, there is a decrease in such biochemical indicators of the composition of amniotic fluid as the level of triglycerides (0.20.1 and 0.30.1 mmol/L, p=0.0036) and cholesterol (0.10.16 and 0.30.2 mmol/L, p=0.0275), gamma-glutamyl transpeptidase activity (34.511 and 48.76.8 U/L, p=0.0261), while the level the lactate (in the main group 3.51.2 and 3.10.9 mmol/L in the control group, p=0.0035), glucose (1.20.6 and 0.60.3 mmol/L, p=0.0002) and nitrogenous substances such as urea (4.51.1 and 3.01.3 mmol/L, p=0.0018) increases. Conclusion. The biochemical composition of amniotic fluid reflects the state of the fetus at birth, and therefore the study of the amniotic fluid is a relevant and accessible method.

PSX-A-3 Late-Breaking: Analysis of serum chemistry for metabolic function in GnRH-II receptor knockdown and littermate control boars

Pigs are the only livestock species encoding functional proteins for both the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II), which are uniquely expressed in reproductive and non-reproductive tissues. To examine the physiological role of the GnRH-II/GnRHR-II system, we produced a swine line with reduced endogenous levels of GnRHR-II (GnRHR-II KD); males exhibit 70% diminished testicular GnRHR-II mRNA levels and 82% reduced circulating testosterone concentrations. Given that testosterone impacts metabolism, blood was collected from GnRHR-II KD (n = 5) and littermate control (n = 5) boars via indwelling jugular catheters, with serum isolated and subjected to veterinary diagnostic panels for metabolic analyte examination (PhysLab, Lincoln, NE). Statistical analyses utilized the MIXED procedure of SAS; the model included line as fixed and litter as random effects. Creatine kinase and blood urea nitrogen (BUN):creatinine ratios were elevated, creatinine was reduced (P &lt; 0.01), and thyroxine tended to be decreased (P &lt; 0.10) in GnRHR-II KD compared with control boars. Glucose, BUN, amylase, and lipase levels were not different. Liver products differed in transgenic versus control boars; levels of lactic dehydrogenase, aspartate and alanine aminotransferases (AST; ALT), and gamma-glutamyl transpeptidase were higher, whereas AST:ALT ratios, total protein, albumin, and globulin levels were lower (P &lt; 0.05) in GnRHR-II KD boars. Albumin:globulin ratios and bilirubin (total and direct) did not differ. Additionally, serum cholesterol was decreased (P &lt; 0.05), non-high density lipoproteins (HDLs) and low density lipoproteins (LDLs) tended to be decreased (P &lt; 0.10), and triglycerides, HDLs, and cholesterol:HDL ratios did not differ between GnRHR-II KD and control males. These data suggest metabolic disruption in GnRHR-II KD boars, which may be due to suppressed gonadal steroidogenesis or ubiquitous knockdown of GnRHR-II expression. Supported by USDA/NIFA AFRI (2017-67015-26508) and Hatch Multistate (NEB-26–244) funds. USDA is an equal opportunity provider and employer.