The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections. RNA PRRs are comprised of TLR3, TLR7, TLR8, RIG-I, MDA5, NLRP3, NOD2, and some other minorities. This review introduces these RNA PRRs by describing the cellular localizations, ligand recognitions, activation mechanisms, cell signaling pathways, and recognition of pathogens; the cross-talks between various RNA PRRs are also reviewed. The deep insights of these RNA PRRs can be utilized to improve anti-viral immune response. © 2017 IUBMB Life, 69(5):297-304, 2017.

Doxorubicin (DOX), a widely used anti-tumor drug, can give rise to severe cardiotoxicity by oxidative stress and cell apoptosis, which restricts its clinical application. α-Linolenic acid (ALA) has been shown to serve as a potent cardioprotective agent. The aim of this study was to explore the protective effects of ALA on DOX-induced cardiotoxicity and the underlying molecular mechanisms for this cardioprotection in rats. Rats were randomly divided into four groups and administrated with normal saline, ALA (500 µg/kg), DOX (2.5 mg/kg), or ALA (500 µg/kg) plus DOX (2.5 mg/kg) for 17 days. The results showed that DOX treatment significantly increased the heart weight/body weight, liver wet weight (WW)/dry weight (DW), lung WW/DW, serum levels of brain natriuretic peptide, creatine kinase-MB, lactate dehydrogenase, and cardiac troponin I, myocardial necrosis and myocardial malondialdehyde content, and induced the mRNA expression of Nrf2 in the nucleus, cleaved caspase-3, Bax, and superoxide dismutase (SOD). In addition, DOX led to a significant decrease in left ventricular end-diastolic volume, stroke volume, ejection fraction, SOD, glutathione-peroxidase, catalase, as well as the expression of Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, phospho-AKT, phospho-ERK, and Bcl-2. Co-treatment with ALA significantly eliminated these changes induced by DOX except further reduction of Keap1 and elevation of Nrf2 and SOD mRNA. These results showed the cardioprotective effects of ALA on DOX-induced cardiotoxicity in rats. The mechanisms might be associated with the enhancement of antioxidant defense system through activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal regulated kinase pathway. Our results suggested a promising future of ALA-based preventions and therapies for myocardial damage after administration of DOX.

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A direct cobalt-catalyzed oxidative coupling between C(sp2)–H in unactivated benzamides and C(sp3)–H in simple alkanes, ethers and toluene derivatives was explored.