Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation

Improved Synthesis of Cellulose Carbamates with Minimum Urea Based on an Easy Scale-up Method

Cellulose carbamates (CCs) were successfully prepared from cellulose/urea (CU) mixtures based on an easy scale-up method and minimum urea. Urea content and the reaction conditions on the nitrogen content of the reacted CU (RCU) mixtures and CCs were systematically investigated. RCU mixtures and CCs were characterized with elemental analysis, Fourier transform infrared spectroscopy, X-ray diffraction, NMR spectrometry and solubility testing. The result indicated that almost all of urea was involved in the derivatization reaction and cellulose was converted into CC with absence of byproducts. The nitrogen content of CCs increased with an increase of the urea content and the reaction temperature, as well as the reaction time. CCs retained the cellulose I crystalline, and the degree of polymerization hardly changed with the reaction conditions. CCs prepared from CU mixtures with the urea content of 3.4–4.6 wt % displayed good solubility in NaOH/ZnO aqueous solutions. Especially, RCU mixtures without washing could be also well dissolved in NaOH/ZnO solutions and its solubility could reach 97%. This work provided a simple, pollution-free and economic pathway for preparing CCs, which is expected to be useful for the CarbaCell process

Wavelength-Tuneable Fluorescent Carbon Dots for Nucleic Acid Imaging

Nucleic acid is one of the most important substances in organisms, and its dynamic changes are closely related to physiological processes. Nucleic acid labeling is conducive to providing important information for the early diagnosis and treatment of pathophysiological processes. Here, we utilized the transfer mechanism between carbon sources and CDs to synthesize wavelength-adjustable N-CDs for the nucleic acid image. Along with the increased graphite nitrogen (from 10.6 to 30.1%) gradually by the precise design of the nitrogen structure in carbon sources (e.g., primary amines, secondary amines, tertiary amines, and liking graphite-nitrogen), the energy gap of CDs reduced, resulting in adjustable wavelength from visible to near-infrared range (from 461 nm/527 nm to 650 nm/676 nm). Furthermore, N-CDs exhibited a selective affinity for nucleic acids, especially RNA. Therefore, N-CDs support an efficient platform for real-time tracking of RNA dynamic changes in cells

L-arabinose exerts probiotic functions by improving gut microbiota and metabolism in vivo and in vitro

Prior investigations have primarily focused on the impact of L-arabinose on gut microbiota, with limited exploration into the dual mechanisms of L-arabinose on microbiota and metabolism both in vivo and in vitro. Thus, this study aimed to elucidate the anti-inflammatory effects of 5 % L-arabinose under different diet in mice. Additionally, a colon simulation system (CDMN) with utilizing 1.72 % (w/v) L-arabinose in the lumen and mucus layers, to provide further insights into the underlying mechanisms. The results revealed that L-arabinose significantly altered the gut microbiome structure, particularly elevating Bifidobacterium and short-chain fatty acids (SCFAs) both in vivo and in vitro. Subsequent in vitro experiments confirmed that L-arabinose increased the relative abundance of SCFAs-producing bacteria, facilitated linoleic acid metabolism, and enhanced downstream metabolites (12,13-DHOME, 9,10-DHOME), potentially mediated by Bifidobacterium in the descending colon. These findings underscore the role of L-arabinose in modulating intestinal flora and metabolism, thereby promoting intestinal and body health

Design, Synthesis, and Biological Evaluation of Mitochondria-Targeted Flavone–Naphthalimide–Polyamine Conjugates with Antimetastatic Activity

Approximately 90% of cancer-associated deaths result from disseminated tumors, indicating the ineffectiveness of current therapies and the imperative need of antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide moieties was constructed by using a fragment-based drug design and a series of eight flavone–naphthalimide–polyamine conjugates were synthesized. <i>In vitro</i> evaluation revealed that compound <b>6c</b> with a homospermidine motif displayed better cell selectivity between cancerous and normal liver cells than amonafide did. The <i>in vivo</i> assays on two hepatocellular carcinoma (HCC) models verified that <b>6c</b> potently suppressed pulmonary metastasis with improved organ indexes compared to amonafide. Various experiments showed that <b>6c</b> as a potential fluorescent chemical probe could target the mitochondria. Preliminary investigation into the mechanism of action of <b>6c</b> indicated that it might harness a polyamine transporter for cell entrance, localize in the mitochondria, selectively cause reactive oxygen species (ROS) overproduction in hepatoma cells instead of normal liver cells, and finally lead to HCC cell apoptosis and migration inhibition via multiple ROS-mediated signaling pathways