International immunopharmacology
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Int. Immunopharmacol. · Jun 2018
Review Meta AnalysisThe risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis.
We performed a systematic review and meta-analysis to evaluate the risk of immune-related endocrine disorders associated with PD-1 inhibitors therapy for solid tumors. ⋯ Both nivolumab and pembrolizumab therapy could result in a higher risk of all-grade immune-related endocrine disorders than chemotherapy. Nivolumab and ipilimumab combination therapy could result in an even higher risk of all-grade immune-related endocrine disorders than ipilimumab or nivolumab alone. Awareness of these side effects could guide clinicians to better manage the patients treated with anti-PD-1 inhibitors therapy for solid tumors.
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Int. Immunopharmacol. · Jun 2018
C5a receptor1 inhibition alleviates influenza virus-induced acute lung injury.
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). ⋯ The results showed that blocking the C5a-C5aR1 axis alleviated ALI by inhibiting endothelial cell activation and dampening the host immune response (i.e., reduced TNF-α, IL-1β, IL-6, IP-10, MCP-1, IL-12p70, and IFN-γ concentrations in plasma), particularly CTL-mediated immunopathology. Furthermore, blockade of the C5a-C5aR1 axis inhibited viral replication in lung tissue. Taken together, the results indicate that the C5a-C5aR1 axis plays an important role in the outcome of ALI induced by influenza virus infection and that regulation of complement activation, particularly the C5aR1 inhibition, is a promising intervention and adjunctive treatment.
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Int. Immunopharmacol. · Jun 2018
20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis.
Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. ⋯ Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage.