New flavonoid glycosides from Xanthium strumarium with their protein tyrosine phosphatase 1B inhibitory activity.

Two new flavonoid glycosides named 6-hydroxy-3-methoxy-apigenin 7-O-α-ʟ-rhamnopyranoside (1) and 3-hydroxyl-apigenin 8-C-ß-ᴅ-xylopyranoside (2), along with five known compounds (3-7), were isolated from Xanthium strumarium. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All compounds were evaluated for in vitro inhibitory activity against PTP1B. Among them, compounds 1 and 5 showed significant inhibitory activity on PTP1B with IC50 values of 11.3 ± 1.7 and 8.9 ± 0.7 µM, respectively.

One pair of new cyclopentaisochromenone enantiomer from Alternaria sp. TNXY-P-1 and their cytotoxic activity.

One pair of new cyclopentaisochromenone derivatives, (+)-(S)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1a) and (-)-(R)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1b), together with seven known analog 2‒8, were isolated from a rice solid culture of the endophytic fungus Alternaria sp. TNXY-P-1, obtained from fresh leaf of Arisaema heterophyllum. Their structures were elucidated on the basis of detailed 1D, 2D NMR, and HRESIMS analysis. Among them, compounds 1a and 1b were enantiomers separated from 1 by chiral HPLC. The absolute configurations of 1a and 1b were assigned by quantum chemical calculations of the electronic circular dichroic spectra. All isolated compounds were evaluated for cytotoxic activities. Interestingly, enantiomers (+)-1a and (-)-1b showed distinct selective antitumor activities against HL-60 cell lines with IC50 values of >200, 75.3 µM, respectively.

Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer.

BACKGROUND: The relationship between hepatitis B surface antigen (HBsAg)-positive carrier status and liver cancer has been extensively studied. However, the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown. The epigenetic modification of DNA hydroxymethylation is critical in tumor development. Further, 5-hydroxymethylcytosine (5hmC) is an important base for DNA demethylation and epigenetic regulation. It is also involved in the assembly of chromosomes and the regulation of gene expression. However, the mechanism of action of 5hmC in HBsAg-positive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated. AIM: To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma (HCC) progression from cirrhosis. METHODS: Forty HBsAg-positive carriers, forty patients with liver cirrhosis, and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants. Free DNA was extracted using a cf-DNA kit. cfDNA was extracted by 5hmC DNA sequencing for principal component analysis, the expression profiles of the three groups of samples were detected, and the differentially expressed genes (DEGs) modified by hydroxymethylation were screened. Bioinformatic analysis was used to enrich DEGs, such as in biological pathways. RESULTS: A total of 16455 hydroxymethylated genes were identified. Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients, of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers. Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes, of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis. These genes may have potential loci that are undiscovered or unelucidated, which contribute to the development and progression of liver cancer. Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion. The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2. CONCLUSION: The occurrence and development of liver cancer involves multiple genes and pathways, which may be potential targets for preventing hepatitis B carriers from developing liver cancer.

Phytochemical investigation of the fruits of Xanthium strumarium and their cytotoxic activity.

Eight pentacyclic triterpenoids including two new ones (1, 2) were isolated from the fruits of Xanthium strumarium. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated for in vitro cytotoxic activity on HepG2, A549, HCT116 and SW480 cancer cells. Among them, the new compound 2 was found to exhibit significant cytotoxic activity on A549, HCT116 and SW480 cancer cells with IC50 values of 9.68, 4.27 and 7.58 µM, respectively. Further, 2 was selected for cell cycle analysis and results revealed that 2 could cause HCT116 cell cycle arrest in G1 phase. In addition, Annexin V-FITC/PI staining assay showed that 2 could induce the death of HCT116 cells.

Two new ditetrahydrofuran lignans from Artemisia sieversiana.

Two new ditetrahydrofuran lignans, named sieverlignans A and B (1 and 2), together with six known ones (3-8), were isolated from the aerial parts of Artemisia sieversiana. Their structures were established on the basis of spectroscopic analysis including HRMS, NMR spectra and circular dichroism experiments. All the compounds were evaluated for their anti-neuroinflammatory effects on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compound 2 exhibited the significant activity with its IC50 value of 11.9 ± 0.8 µM, respectively, compared to a positive control quercetin with its IC50 value of 16.0 ± 1.1 µM.

Terpenoid and phenolic constituents from the roots of Ilex pubescens.

Five new metabolites, including two monoterpene glycosides Pubescenosides L-M (1-2) and three phenolic glycosides, Pubescenosides N-P (3-5), along with nineteen known ones, including liganoids, hemiterpenoids and caffeoylquinic acid derivates, were isolated from the roots of Ilex pubescens. Their structures were elucidated from extensive spectroscopic analysis, including 1D and 2D NMR experiments. This study is the first to report monoterpene glycosides with ß-pinene aglycone in Aquifoliaceae. Nine of these compounds were evaluated in vitro for their anti-platelet aggregation activities. Among them, compounds 3 and 4 showed moderate inhibitory activities on ADP-induced blood platelet aggregation [inhibition (%): 32.3 and 33.6, respectively] as compared to aspirin.

[Recombinant human brain natriuretic peptide on the cardiac hemodynamics and renal function in dogs with heart failure].

AIM: To study the effects of rhBNP on the cardiac hemodynamics and renal function in dogs with heart failure. METHODS: Congestive heart failure in dogs was induced by either rapid ventricular pacing (RVP), 250 beats.min-1 for 7-14 days or by thoracic inferior vena cava constriction (TIVCC) to 1/2 its original diameter. When remarkable hemodynamic changes appeared rhBNP was infused intravenously at the dosage of 10, 30 and 100 ng.kg-1.min-1, each dose lasting 30 min. RESULTS: In dogs (n = 7) with RVP heart failure, intravenous infusion of rhBNP at 10-100 ng.kg-1.min-1, caused decreases in mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), LVdP/dtmax, pulmonary arterial pressure (PAP), left ventricular end diastolic pressure (LVEDP), total peripheral vascular resistance (TPR) and renal vascular resistance (RVR) dose-dependently, without significant changes in cardiac output (CO), LVdp/dt/P, left ventricular work (LVW), renal blood flow (RBF) and heart rate (HR). This suggested that rhBNP reduced the pre-load and after-load of the dogs with congestive heart failure but showed no distinct effect on the contractility of the heart. In dogs (n = 7) with TIVCC heart failure, there were remarkable decreases in MAP and LVEDP following the rhBNP infusion, without further reduction of CO, but no marked change in HR, LVSP, LVdP/dtmax, RAP and TPR. In both animal models of heart failure, there were significant increases in urine volume and sodium excretion which were more significant in TIVCC dogs than in RVP dogs. CONCLUSION: rhBNP reduced the pre-load and after-load in dogs with heart failure and showed remarkable diuretic effect, but did not affect the contractility of the heart.

[Effects of recombinant human brain natriuretic peptide and milrinone on cardiac hemodynamics and renal function in anesthetized dog].

AIM: To study the effects of rhBNP and milrinone on the cardiac hemodynamics and renal function in anesthetized dogs. METHODS: The actions of rhBNP given cumulatively i.v. 10, 30 and 100 ng.kg-1 for 30 min and milrinone of single dose (100 micrograms.kg-1, i.v.) on cardiac hemodynamics and renal function were studied in anesthetized open-chest dogs. RESULTS: In anesthetized dogs (n = 7) intravenous infusion of rhBNP at 10-100 ng.kg-1, caused decreases in mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), LVdp/dtmax, pulmonary arterial pressure (PAP), left ventricular end diastolic pressure (LVEDP), total peripheral resistance (TPR) and renal vascular resistance (RVR) dose-dependently, without significant changes in cardiac output (CO), LV(dp/dt)/P, renal blood flow (RBF) and heart rate (HR), increases in urinary volume and sodium excretion. In anesthetized dogs (n = 6), there were remarkable decreases in MAP, LVEDP, PAP, TPR, RBF, RVR and urinary volume following the MIL (100 micrograms.kg-1, i.v.), with significant increases of LVSP, +/- LVdp/dtmax, HR and CO, but no marked changes in urinary volume and sodium excretion. CONCLUSION: rhBNP reduces the pre-load and after-load in the anaesthetized dogs but showed no distinct effect on the contractility of the heart. Positive inotropic and chronotropic actions have been demonstrated after intravenous injection of milrinone 100 micrograms.kg-1 in anesthetized dogs.