Macrophages, which are key cellular components of the liver, have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases. Upon liver injury, resident Kupffer cells (KCs) sense disturbances in homeostasis, interact with hepatic cell populations and release chemokines to recruit circulating leukocytes, including monocytes, which subsequently differentiate into monocyte-derived macrophages (MoMϕs) in the liver. Both KCs and MoMϕs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases. The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases. In this review, we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease.

Background:Exercise tolerance and cardiac output have a major impact on the quality of life (QOL) of patients experiencing heart failure (HF). Home-based cardiac rehabilitation can significantly improve not only exercise tolerance but also peak oxygen uptake ( peak), and the QOL in patients with HF. The aim of this prospective study was to evaluate the beneficial effects of home-based cardiac rehabilitation on the quality of medical care in patients with chronic HF.Methods:This study was a randomized prospective trial. HF patients with a left ventricular ejection fraction (LVEF) of less than 50% were included in this study. We randomly assigned patients to the control group (n = 18) and the interventional group (n = 19). Within the interventional group, we arranged individualized rehabilitation programs, including home-based cardiac rehabilitation, diet education, and management of daily activity over a 3-month period. Information such as general data, laboratory data, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk Test (6MWT) results, and the scores for the Minnesota Living with Heart Failure Questionnaire (MLHFQ) before and after the intervention, was collected from all patients in this study.Results:Patients enrolled in the home-based cardiac rehabilitation programs displayed statistically significant improvement in peak (18.2 ± 4.1 vs 20.9 ± 6.6 mL/kg/min, P = .02), maximal 6-Minute Walking Distance (6MWD) (421 ± 90 vs 462 ± 74 m, P = .03), anaerobic threshold (12.4 ± 2.5 vs 13.4 ± 2.6 mL/kg/min, P = .005), and QOL. In summary, patients receiving home-based cardiac rehabilitation experienced a 14.2% increase in peak, a 37% increase in QOL score, and an improvement of 41 m on the 6MWD test. The 90-day readmission rate for patients reduced to 5% from 14% after receiving cardiac rehabilitation.Conclusion:Home-based cardiac rehabilitation offered the most improved results in functional capacity, QOL, and a reduced the rate of readmission within 90 days.

Nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidants has been implicated to have protective roles in ischemia-reperfusion (I/R) injury in many animal models. However, the in vivo effects of CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole), a Nrf2 activator, in hepatic I/R injury is lacking and its exact molecular mechanisms are still not very clear. The goals of this study were to determine whether CDDO-Im can prevent liver injury induced by I/R in the mouse, and to elucidate the molecular target of drug action. Mice were randomly equally divided into two groups and administered intraperitoneally with either DMSO control or CDDO-Im (2 mg/kg) 3 h before subjected to 90-min hepatic 70% ischemia followed by reperfusion. Subsequently, the Liver and blood samples of these mice were collected to evaluate liver injury. CDDO-Im pretreatment markedly improve hepatic I/R injury by attenuating hepatic necrosis and apoptosis, reducing reactive oxygen species (ROS) levels and inflammatory responses, and ameliorating mitochondrial dysfunction. Mechanistically, by using Nrf2 Knockout mice and hemeoxygenase 1 (HO-1) inhibitor, we found that these CDDO-Im protection effects are attributed to enhanced autophagy, which is mediated by activating Nrf2/HO-1 pathway. By accelerating autophagy and clearance of damaged mitochondria, CDDO-Im reduced the mtDNA release and ROS overproduction, and in turn decreased damage-associated molecular patterns induced inflammatory responses and the following secondary liver injury. These results indicate that by enhancing autophagy, CDDO-Im-mediated activation of Nrf2/HO-1 signaling could be a novel therapeutic strategy to minimize the adverse effects of hepatic I/R injury.

Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases.