Orthotopic liver transplantation is the only effective treatment for liver failure but limited with shortage of available donor organs. Recent studies show promising results of mesenchymal stem cells (MSCs)-based therapies. We systematically investigate the therapeutic effects of MSCs or MSC-conditioned medium (MSC-CM) in ameliorating fulminant hepatic failure (FHF) and chronic liver fibrosis in mice. In addition, extensive flow cytometry analysis of spleens from vehicle and MSC- and MSC-CM-treated mice was applied to reveal the alteration of inflammatory state. In FHF model, MSCs treatment reduced remarkably the death incidents; the analysis of gross histopathology showed that control livers were soft and shrunken with extensive extravasated blood, which was gradually reduced at later time points, while MSC–treated livers showed gross pathological changes, even 24 h after MSC infusion, and hematoxylin and eosin staining revealed dramatical hepatocellular death with cytoplasmic vacuolization suppressed by MSCs treatment; flow cytometry analysis of total lymphocytes showed that macrophages (F4/80) infiltrated into control livers more than MSC-treated livers; by contrast, MSC-CM partially ameliorates FHF. In chronic liver injury model, MSC and MSC-CM both suppressed fibrogenesis and necroinflammatory, and the later was better; activation of hepatic stellate cells (α-SMA) was inhibited; glycogen synthesis and storage (indicated by periodic acid-Schiff -staining) was improved; liver regeneration (Ki67) was promoted while liver apoptosis (TUNEL) was reduced. In the in vitro, MSCs promote macrophage line RAW264.7 apoptosis and MSC-CM promotes apoptosis and inhibits proliferation of HSC line LX-2. We also found that MSCs and MSC-CM could improve spleen; MSC-CM increased levels of Th2 and Treg cells, and reduced levels of Th17 cells, whereas levels of Th1 cells were unchanged; comparatively, MSC treatment did not affect Th17 and Treg cells and only slightly alters inflammatory state; MSC and MSC-CM treatment both substantially down-regulated macrophages in the spleens. Both MSCs and MSC-CM exert therapeutic effects by acting on various key cells during the pathogenesis of FHF and chronic fibrosis, stimulating hepatocyte proliferation and suppressing apoptosis, down-regulating infiltrating macrophages, converting CD4+ T lymphocyte system into an anti-inflammatory state, and facilitating hepatic stellate cell death.

Macrophages are located in essentially all tissues due to their “janitor” function. Macrophages can exert either anti- or pro-tumor activities depending upon the specific tumor microenvironment they inhabit. Substantial evidence indicates that macrophages, owing to their plasticity, can be reeducated to adopt a protumoral phenotype within a tumor microenvironment through the help of growth factors in the microenvironment and intercellular interactions. As the lethality of malignant melanoma is due to its aggressive capacity for metastasis and resistance to therapy, considerable effort has gone toward treatment of metastatic melanoma. In the present review, we focus on the pro-tumor activities of macrophages in melanoma. Based upon the information presented in this review it is anticipated that new therapies will soon be developed that target pro-tumor activities of macrophages for use in the treatment of melanoma.

Gastric cancer (GC) is a malignant tumor that negatively impacts human health, which typically presents in the advanced stages of disease in the majority of patients. Despite the development of combination chemotherapy, only a modest survival advantage is gained in patients with GC treated by this method. Recently, cancer immunotherapies have received considerable attention as a viable therapeutic option for GC. Specifically, the immune checkpoint inhibitors, chimeric antigen rector (CAR)‑T cells and tumor vaccines, represent immunotherapies that have exhibited promising effects in the treatment of GC. A number of clinical trials have employed either immuno‑oncology monotherapies or combination therapies to improve the overall survival time (OS) and objective response rate (ORR) of patients with GC. The current review presents a summary of the clinical effects of checkpoint inhibitors, including CAR‑T and tumor vaccines, in the treatment of GC.

Embelin is an active component isolated from Embelia ribes Burm. In this study, we explored the protective effects of embelin on acute liver injury. An animal model of acute liver injury was established via administration of a single injection of thioacetamide (TAA) (300 μg/g body weight) to adult mice. Embelin was administered by intragastric gavage at 50 μg/g body weight starting 2 days before TAA administration and continuing throughout the study. Survival of the mice was analyzed by the Kaplan-Meier method using the log-rank test. The acute liver injury protocol was repeated and the remaining mice were analyzed at indicated times. Hematoxylin and eosin staining and picrosirius red staining were used to examine necrosis/inflammation and liver healing, respectively. Liver function was assessed by serum alanine aminotransferase/alkaline phosphatase activity. Hepatic cleaved caspase-3 and F4/80 expression levels were examined via immunostaining. Statistical analysis was performed with GraphPad Software. The survival and liver function of the mice were markedly better in the group treated with embelin prior to TAA toxication than in the TAA toxication-only group. Embelin significantly reduced TAA-induced hepatic necrosis/apoptosis. Massive inflammatory cell infiltration, which is consistent with hepatic fibrogenesis (a healing process), occurred earlier in the embelin-treated recovery group than in the spontaneous recovery group. Moreover, macrophage activities increased more rapidly with embelin treatment. In summary, embelin can protect against acute liver injury. Its therapeutic value warrants further exploration.

Increasing evidence has accrued which indicates that mesenchymal stem cells (MSCs) have a potential clinical value in the treatment of certain diseases. Globally, nonalcoholic steatohepatitis (NASH) is a widespread disorder. In the present study, MSCs were isolated successfully from compact bone and a mouse model of NASH was established as achieved with use of a methionine-choline deficient (MCD) diet. Compact bone-derived MSCs transplantation reduced MCD diet-induced weight loss, hepatic lipid peroxidation, steatosis, ballooning, lobular inflammation and fibrogenesis. It was shown that MSCs treatment hampered MCD diet-induced proliferation of CD4+ IFN-γ+ and CD4+IL-6+ T spleen cells. In addition, CD4+IL-17+ lymphocytes that associated with anti-inflammation show little change in MCD as well as in MCD+MSCs splenocytes. We conclude that MSCs may have a potential clinical value upon NASH, through their capacity to suppress activation of CD4+ IFN-γ+ and CD4+IL-6+ lymphocytes.

Metabolic reprogramming promotes glioblastoma cell migration and invasion. Integrin αvβ3 is one of the major integrin family members in glioblastoma multiforme cell surface mediating interactions with extracellular matrix proteins that are important for glioblastoma progression. The role of αvβ3 integrin in regulating metabolic reprogramming and its mechanism of action have not been determined in glioblastoma cells. Integrin αvβ3 engagement with osteopontin promotes glucose uptake and aerobic glycolysis, while inhibiting mitochondrial oxidative phosphorylation. Blocking or downregulation of integrin αvβ3 inhibits glucose uptake and aerobic glycolysis and promotes mitochondrial oxidative phosphorylation, resulting in decreased migration and growth in glioblastoma cells. Pharmacological inhibition of focal adhesion kinase (FAK) or downregulation of protein arginine methyltransferase 5 (PRMT5) blocks metabolic shift toward glycolysis and inhibits glioblastoma cell migration and invasion. These results support that integrin αvβ3 and osteopontin engagement plays an important role in promoting the metabolic shift toward glycolysis and inhibiting mitochondria oxidative phosphorylation in glioblastoma cells. The metabolic shift in cell energy metabolism is coupled to changes in migration, invasion, and growth, which are mediated by downstream FAK and PRMT5 in glioblastoma cells.