Zinc is an essential trace element for bone growth and bone homeostasis in the human body. Bone mesenchymal stem cells (BMSCs) are multipotent progenitors existing in the bone marrow stroma with the capability of differentiating along multiple lineage pathways. Zinc plays a paramount role in BMSCs, which can be spurred differentiating into osteoblasts, chondrocytes, or adipocytes, and modulates the formation and activity of osteoclasts. The expression of related genes also changed during the differentiation of various cell phenotypes. Based on the important role of zinc in BMSC differentiation, using zinc as a therapeutic approach for bone remodeling will be a promising method. This review explores the role of zinc ion in the differentiation of BMSCs into various cell phenotypes and outlines the existing research on their molecular mechanism.
Nanomedicines are of increasing scrutiny due to their improved efficacy and/or mitigated side effects. They can be integrated with many other therapeutics to further boost the clinical benefits. Among those, herbal medicines are arousing great interest to be combined with nanomedicines to exert synergistic effects in multifaceted mechanisms. The in vivo performance of nanomedicines which determines the therapeutic efficacy and safety is believed to be heavily influenced by the physio-pathological characters of the body. Activation of multiple immune factors, e.g., complement system, phagocytic cells, lymphocytes, and among many others, can affect the fate of nanomedicines in blood circulation, biodistribution, interaction with single cells and intracellular transport. Immunomodulatory effects and metabolic regulation by herbal medicines have been widely witnessed during the past decades, which alter the physio-pathological conditions and dramatically affect in vivo delivery of nanomedicines. In this review, we summarize recent progress of understanding on the in vivo delivery process of nanomedicines and analyze the major affecting factors that regulate the interaction of nanomedicines with organisms. We discuss the immunomodulatory roles and metabolic regulation by herbal medicines and their effects on in vivo delivery process of nanomedicines, as well as the prospective clinical benefits from the combination of nanomedicines and herbal medicines.
Pulmonary artery hypertension (PAH) is a disease with high morbidity and mortality. Cyanidin-3-O-beta-glucoside (Cy-3-g), a classical anthocyanin, has a variety of biological effects. The present study evaluated whether Cy-3-g attenuated PAH, and explored the potential mechanism of action. Rats were injected with monocrotaline (MCT; 60 mg per kg of body weight) and then treated with Cy-3-g (200 or 400 mg per kg of body weight) for 4 weeks. Protein expression was determined in vitro in transforming growth factor-beta 1 (TGF-beta 1)-mediated human pulmonary arterial smooth muscle cells (SMCs). The results indicated that Cy-3-g significantly inhibited the mean pulmonary artery pressure, right ventricular systolic pressure and right ventricular hypertrophy index, as well as vascular remodeling induced by MCT in PAH rats. Further experiments showed that Cy-3-g suppressed the expression of pro-inflammatory factors and enhanced the levels of anti-inflammatory factors. Cy-3-g blocked oxidative stress and improved vascular endothelial injury. Cy-3-g also reduced the proliferation of SMCs. Furthermore, the MCT- and TGF-beta 1-induced increase in TGF-beta 1, phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) and p-cAMP-response element binding protein (CREB) expression was blocked by Cy-3-g treatment in vivo and in vitro. These results indicated that Cy-3-g could prevent vascular remodeling in PAH via inhibition of the TGF-beta 1/p38 MAPK/CREB axis.