Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease.

BACKGROUND: Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. METHODS: This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. RESULTS: This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. CONCLUSIONS: This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.

New cytotoxic alkylated anthraquinone analogues from a soil actinomycete Streptomyces sp. WS-13394.

Four new alkylated anthraquinone analogues (1-4) were isolated from a soil actimomycete Streptomyces sp. WS-13394. The structures of compounds 1-4 were elucidated to be 1,4,6-trihydroxy-8-alkylanthraquinones by means of spectroscopic methods, including UV, one dimensional (1D), 2D-NMR and MS spectrometry. All compounds showed activities against BGC-823 and MCF-7 with IC50 from 0.99 to 3.54 µg/mL, while 2 exhibited cytotoxicity against HepG2, A875, BGC-823 and MCF-7 with IC50 2.29, 4.90, 0.99, and 1.66 µg/mL, respectively.

Pierisformotoxins A-D, polyesterified grayanane diterpenoids from Pieris formosa and their cAMP-decreasing activities.

Four highly acylated diterpenoids, designated as pierisformotoxins A-D (1-4, resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B (1 and 2, resp.) were new highly acylated grayanane diterpenoids, of which the five-membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five-membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP-regulation-activity assay showed that pierisformotoxin C (3) at 10 µM (inhibitory ratio (IR): 10.1%) or 2 µM (9.8%), and pierisformotoxin B (2) at 50 µM (13.9%) significantly decreased the cAMP level in N1E-115 neuroblastoma cells (p<0.05).

Lyonin A, a new 9,10-Secograyanotoxin from Lyonia ovalifolia.

Phytochemical studies on the branches and leaves of Lyonia ovalifolia yielded a new grayanane diterpenoid, lyonin A (1), together with two known compounds, secorhodomollolides A and D (2 and 3, resp.). The structure of 1 was elucidated by combination of 1D- and 2D-NMR, and MS analyses. Compound 1 turned out to be a new, highly O-acylated grayanane diterpenoid, of which ring B has undergone an oxidative cleavage between C(9) and C(10), yielding a system differing from the previously reported grayanane type with a 5/7/6/5 ring system. Results of the cAMP regulation activity assay showed that compounds 2 and 3 at 50 µM induced a significantly decreased cAMP level in N1E-115 neuroblastoma cells (p<0.001), indicating neuropharmacological potential.

Three new highly acylated 3,4-seco-grayanane diterpenoids from the fruits of Pieris formosa.

Phytochemical investigation on the fruits of Pieris formosa resulted in the isolation of three new highly acylated 3,4-seco-grayanane diterpenoids, pierisformotoxins E-G (1-3). Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D-, 2D-NMR, electrospray ionization-mass spectra (ESI-MS) and high resolution (HR)-MS.

New grayanol diterpenoid and new phenolic glucoside from the flowers of Pieris formosa.

A new grayanol diterpenoid, grayanotoxin XXII (1), and a new phenolic glucoside, benzyl 2-hydroxy-4-O-[beta-xylopyranosyl(1'' --> 6')-beta-glucopyranosyl]-benzoate (2), were isolated from the flowers of Pieris formosa. Their structures were determined on the basis of spectroscopic analysis and chemical methods.

Isolation of two new prenylflavonols from Epimedium brevicornum and their effects on cytokine production in vitro.

In an attempt to search for bioactive natural products, two new prenylflavonols, 2''-hydroxy-3''-en-anhydroicaritin (1) and 2''-hydroxy-beta-anhydroicaritin (2), were isolated from the Chinese medicinal herb Epimedium brevicornum. Their structures were determined by 1D and 2D NMR spectroscopic analysis. The effects of compounds 1 and 2 on cytokine production in vitro were investigated. Compound 1 could significantly downregulate tumor necrosis factor-alpha (TNF-alpha) production and increase interleukin-10 (IL-10) production. These results suggested that compound 1 may have anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated mouse macrophages. In addition, the biogenetic relationships among compounds 1 and 2 are discussed.