Novel kinase 1 regulates CD8+T cells as a potential therapeutic mechanism for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.

Semi-Synthesis of Flavonoid Glycosides and Their Anti-Inflammatory and Antitumor Activities towards Triple Negative Breast Cancer.

BACKGROUND: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. OBJECTIVE: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti-inflammatory activities of these compounds. METHODS: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti-inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) production in LPS-induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, 1 H-NMR, and 13 C-NMR, and their cytotoxicity on the human triple-negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. RESULTS: Most of the compounds markedly reduced NO production in LPS-stimulated murine macrophages at the tested concentrations in a dose-dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti-inflammatory activities against NO production in LPS-induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF-α and IL-6 in a concentration-dependent manner. Most of the tested compounds showed remarkable anti-human TNBC activities. Compounds 1b-1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC50 values were all below 16.61 µM. In addition, compound 1l was the most cytotoxic with IC50 values of 1.38±0.31 µM, while the other compounds were inactive with inhibition rates <50 % at the highest concentration tested (20 µM). CONCLUSIONS: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS-stimulated murine macrophages at concentrations of 15 to 60 µM, and the inhibition generally increased in a dose-dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.

[Pharmacokinetics and bioavailability of ginsenoside Rg1 in rats].

OBJECTIVE: To investigate the pharmacokinetics and bioavailability of ginsenoside Rg1 in rats. METHODS: Ginsenoside Rg1 was oral administered or intravenous administered to each rat. The plasma concentration of ginsenoside Rg1 was estimated by RP-HPLC. 3P97 software was used to calculate pharmacokinetic parameters. RESULTS: Main parameters of ginsenoside Rg1 after oral or intravenous administered were: AUC(0 --> t), 322.70 +/- 20.78, 99.76 +/- 8.91 microg x h/mL, CL 0.08 +/- 0.02, 3.01 +/- 0.69 L/(kg x h), V 0.23 +/- 0.01, 22.75 +/- 2.09 L/kg, t1/2alpha 0.48 +/- 0.18, 0.87 +/- 0.21 h, t1/2beta 19.57 +/- 2.81, 18.68 +/- 2.74 h, MRT6.91 +/- 0.99, 8.15 +/- 1.05 h(-1), respectively. The relative oral bioavailability of ginsenoside Rg1 was 2.5%. CONCLUSION: The oral bioavailability of ginsenoside Rg1 is very low.