Synthesis and Application of a pH-Responsive Functional Metal-Organic Framework: In Vitro Investigation for Delivery of Oridonin in Cancer Therapy.

Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess intriguing biological properties; however, the quick clearance from plasma and limited solubility in water restricts its use as a drug. Several metal-organic frameworks (MOFs), having big surfaces and large pores, have recently been considered promising drug transporters. The zeolitic imidazolate framework-8 (ZIF-8), a form of MOF consisting of 2-methylimidazole with zinc ions, is structurally stable under physiologically neutral conditions, while it can degrade at low pH values such as in tumor cells. Herein, a nanosized drug delivery system, Ori@ZIF-8, was successfully designed for encapsulating and transporting oridonin to the tumor site. The drug loading of the prepared Ori@ZIF-8 was 26.78%, and the particles' mean size was 240.5 nm. In vitro, the release of Ori@ZIF-8 exhibited acid sensitivity, with a slow release under neutral conditions and rapid release of the drug under weakly acidic conditions. According to the in vitro anti-tumor experiments, Ori@ZIF-8 produced higher cytotoxicity than free Ori and induced apoptosis in A549 cancer cells. In conclusion, Ori@ZIF-8 could be a potential pH-responsive carrier to accurately release more oridonins at the tumor site.

Three metal complexes with a pyridyl Schiff base: cytotoxicity, migration and mechanism of apoptosis.

Three metal complexes [CuL(NO3)]n (1), [Cd(HL)(NO3)2]n (2) and [EuL(HCOOH)(H2O)(NO3)2] (3) were synthesized with a pyridyl Schiff ligand L (N'-[(1E)-pyridin-2-ylmethylidene]pyridine-4-carbohydrazide). A crystallographic study revealed that complexes 1 and 2 have a chain structure, and complex 3 is a zero-dimensional monomer. In vitro cytotoxicity studies showed that complex 2 had the best antiproliferative activity against SMMC-7721 cells and complex 3 had the best antiproliferative activity against MDA-MB-231 cells with single-digit IC50 values, both exceeding those of the control drug cisplatin by far. The cell invasion and migration ability through the transwell assay and wound-healing assay showed that the selected complexes could inhibit the invasion and migration of cancer cells. The Hoechst staining assay and ROS generation assay with SMMC-7721 cells indicated that the cytotoxic effects of complex 2 involved apoptosis induction through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of complex 2 on SMMC-7721 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. In addition, complex 2 showed significant inhibition against B. dysentery with an inhibition circle diameter of 24 mm.

Cognitive decline trajectories and influencing factors in China: A non-normal growth mixture model analysis.

BACKGROUND: With the increase in the aging population worldwide, cognitive decline has become an important research topic. The purpose of this study is to examine the cognitive development trajectories and influencing factors of different latent classes of Chinese elderly people. This will provide us with effective guidance for prevention and intervention. METHODS: Four waves of data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were collected and included 2440 Chinese elderly individuals. The cognitive function of elderly individuals was measured using the Mini Mental State Examination (MMSE). A nonnormal Growth Mixture model (GMM) with five time-invariant covariates was used to identify the different trajectories of cognitive decline in elderly individuals. RESULTS: Three latent decline trajectory groups were identified: stable cognitive group (SCG), high initial level - cognitive decline group (HIL-CDG), and high initial level - cognitive decline group (LIL-CDG). Elderly women were more likely to be assigned to a lower level subgroup than men. People who smoked and played cards or mahjong were more likely to be assigned to a cognitively stable group. CONCLUSION: Education may help raise the upper limit of cognition. Smoking may impair cognitive upper limit. A small amount of alcohol intake and participation in cognitive and physical activities may help the elderly to delay cognitive decline in their later years.