Yong Yuan

Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.

) had reduced oxidative stress and inflammatory factors when L-theanine was administered both long-term and as a preventative treatment. Our L-theanine intervention countered the reduction in growth and feed intake of mice under heat stress and reversed liver and jejunum tissue damage. Moreover, L-theanine countered the increase in inflammatory factors TNF-α, IL-6, and IL-1β and antioxidant enzymes SOD and CAT; it also counteracted GSH-Px inactivation, the upregulation of AST and ALT enzyme activity, and MDA production. The mechanism of action may involve mediation of the P38 signaling pathway, inhibition of MK2 overexpression, and downregulation of p-P65/P65 caused by the overexpression of downstream HSP27. This would inhibit the heat stress-induced imbalance in oxidative stress and inflammatory responses.

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (> 5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo.

Reconstruction of biophysically detailed computer models for simulating electrical activities of heart cells provides a powerful tool to systematically investigate the ionic mechanisms underlying the genesis and control of cardiac rhythms. However, the fact that there is no unified or standard architecture for computational cell models, which were built by different research groups with specific purposes, obstructed profound applications of these models. In this study, we employed object-oriented design patterns to redesign and reconstitute the cell models and provided a more flexible, portable, and expansible infrastructure for modeling computational cell models. Meanwhile, using the proposed methods, a simulation platform has been developed for electrical activities of cell models with aims to offer a user-friendly interface to study the electrical activities of cardiac cells under various physiological and pathological conditions. Both the proposed design methods and the developed system were validated and effective by testing several typical cell models.