Search

SYHA1813 is a potent multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs)/colony-stimulating factor 1 receptor (CSF1R). This study aimed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of escalating doses of SYHA1813 in patients with recurrent high-grade gliomas (HGGs) or advanced solid tumors. This study adopted a combination of accelerated titration and a 3 + 3 design for dose escalation, with a starting dose of 5 mg once daily. The dose escalation continued at successive dose levels until the maximum tolerated dose (MTD) was determined. A total of 14 patients were enrolled and treated, including 13 with WHO grade III or IV gliomas and 1 with colorectal cancer. Two patients experienced dose-limiting toxicities (grade 4 hypertension and grade 3 mucositis oral) at 30 mg SYHA1813. The MTD was defined as 15 mg once daily. Hypertension (n = 6, 42.9%) was the most frequent treatment-related adverse event. Among evaluable patients (n = 10), 2 (20%) patients achieved partial response, and 7 (70%) had stable disease. The exposure increased with increasing doses within the studied dose range of 5 to 30 mg. Biomarker assessments demonstrated significant reductions in the levels of soluble VEGFR2 (P =.0023) and increases in the levels of VEGFA (P =.0092) and placental growth factor (P =.0484). The toxicities of SYHA1813 were manageable, and encouraging antitumor efficacy was observed in patients with recurrent malignant glioma. This study is registered with the Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx; identifier ChiCTR2100045380). [ABSTRACT FROM AUTHOR]

Cryptotanshinone (CT) is an extract from the traditional Chinese medicine Salvia miltiorrhiza, which inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. This study aims to determine the antibacterial mechanisms of CT by integrating bioinformatics analysis and microbiology assay. The microarray data of GSE13203 was retrieved from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) of S. aureus strains that were treated with CT treatment. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify the potential target of CT. Data mining on the microarray dataset indicated that pyruvate kinase (PK) might be involved in the antimicrobial activities of CT. The minimum inhibition concentrations (MICs) of CT or vancomycin against the MRSA strain ATCC43300 and seven other clinical strains were determined using the broth dilution method. The effects of CT on the activity of PK were further measured. In vitro tests verified that CT inhibited the growth of an MRSA reference strain and seven other clinical strains. CT hampered the activity of the PK of ATCC43300 and five clinical MRSA strains. CT might hinder bacterial energy metabolism by inhibiting the activity of PK. [ABSTRACT FROM AUTHOR]

Until now, there have been many reports on the regulation of inorganic metal ions on the catalytic activity of nanozymes, but few reports on the regulation of anions (such as NO2−) on enzyme activity. In this work, a copper-molybdenum doped carbon dots (Cu, Mo-CDs) with peroxidase-like (POD) activity was synthesized by simple one-step microwave digestion method. The Cu, Mo-CDs + NO2− system can promote 3,3′,5,5′-tetramethylbenzidine (TMB) oxidizing to blue oxidative product (oxTMB) due to the formation of ∙NO2 free radical. While Hg2+ was introduced into the system, the POD-like activity of Cu, Mo-CDs + NO2− system was inhibited due to the strong interaction and the electron transfer between Cu, Mo-CDs and Hg2+. The formation of ∙NO2 and the electron transfer capability of Cu, Mo-CDs + Hg2+ were confirmed through ESR spectra and FMN experiments. The bioenzyme-free colorimetric assay based on Cu, Mo-CDs nanozyme is used for detection of NO2− and Hg2+, showing lower detection limit (LOD) of 1.63 µg/L for NO2−, 0.13 µg/L for Hg2+, respectively and good recovery from 90.79 to 108.90%. The work paves a new way to design a nanozyme-based colorimetric protocol for traces NO2− and Hg2+ residues in food analysis. [ABSTRACT FROM AUTHOR]