Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway.

BACKGROUND: Monocytes/macrophages play critical roles in inflammation and cardiac remodeling following myocardial infarction (MI). The cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses by activating α7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. We investigated the effect of α7nAChR on MI-induced monocyte/macrophage recruitment and polarization and its contribution to cardiac remodeling and dysfunction. METHODS: Adult male Sprague Dawley rats underwent coronary ligation and were intraperitoneally injected with the α7nAChR-selective agonist PNU282987 or the antagonist methyllycaconitine (MLA). RAW264.7 cells were stimulated with lipopolysaccharide (LPS) + interferon-gamma (IFN-γ) and treated with PNU282987, MLA, and S3I-201 (a STAT3 inhibitor). Cardiac function was evaluated by echocardiography. Masson's trichrome and immunofluorescence were used to detect cardiac fibrosis, myocardial capillary density, and M1/M2 macrophages. Western blotting was used to detect protein expression, and the proportion of monocytes was measured using flow cytometry. RESULTS: Activating the CAP with PNU282987 significantly improved cardiac function and reduced cardiac fibrosis and 28-day mortality after MI. On days 3 and 7 post-MI, PNU282987 reduced the percentage of peripheral CD172a + CD43low monocytes and the infiltration of M1 macrophages in the infarcted hearts, whereas it increased the recruitment of peripheral CD172a + CD43high monocytes and M2 macrophages. Conversely, MLA exerted the opposite effects. In vitro, PNU282987 inhibited M1 macrophage polarization and promoted M2 macrophage polarization in LPS + IFN-γ-stimulated RAW264.7 cells. These PNU282987-induced changes in LPS + IFN-γ-stimulated RAW264.7 cells were reversed by administering S3I-201. CONCLUSION: Activating α7nAChR inhibits the early recruitment of pro-inflammatory monocytes/macrophages during MI and improves cardiac function and remodeling. Our findings suggest a promising therapeutic target for regulating monocyte/macrophage phenotypes and promoting healing after MI.

A duplex DNA model with regular inter-base-pair hydrogen bonds.

It is well known that base-pair stacking is the main factor in stabilizing DNA duplex and plays an important role in determining DNA sequence-dependence. What is the dominant force in base-pair stacking? This fundamental biological question remains a challenging problem. Here, based on recent studies about the non-planarity of amino groups on DNA bases, we propose a new duplex DNA model, in which all base amino groups are non-planar and participate in forming regular inter-base-pair hydrogen bonds (IBP H-bonds). This model implies that IBP H-bonds are the dominant force stabilizing base-pair stacking and play a crucial role in determining the geometry and physical properties of sequence-dependent twisted stacking between adjacent base pairs. The model presents a new insight into the link, through regular IBP H-bonds, between base-sequence, fine structure and physical properties at dinucleotide step level, and provides an attractively concise, uniform and quantitative interpretation for various experimentally observed DNA sequence-dependent properties in terms of regular IBP H-bonds. It would provide a new approach to understanding the dynamics and underlying mechanisms of DNA sequence-dependent biological processes, sequence-structure-property relationships, DNA strand separation during replication and transcriptions, etc.

First record of Bursaphelenchus rainulfi on pine trees from eastern China and its phylogenetic relationship with intro-genus species.

Bursaphelenchus rainulfi isolated from dead pine trees in Zhejiang, China, is described and illustrated. It also provided some molecular characters of the Chinese population, including the PCR-RFLP and sequences of ITS region and D2-D3 expansion region of the large subunit (LSU) rRNA gene. Both the morphological characters and ITS-RFLP patterns match with the original description. The phylogenetic trees based on the 13 sequences of D2-D3 expansion region of the LSU rRNA gene and ITS region of Bursaphelenchus species were constructed, respectively, with the results showing the similar clades. The phylogenetic relationship based on the molecular data is similar to that with morphological characters. This is the first report of the species on pine wood in eastern China.

Polarity and hydrophobicity interactions in protein synthesis process.

About 30 years ago, experiments found that there are polarity and hydrophobicity (P and H) correlations and affinity between amino acids and their anticodons. Although it is shown that these experimental findings are important for explaining the origins of the genetic code, the great potential of P and H interactions in investigating other bio-functions have not been fully explored. Here, through raising, discussing and answering seven relevant questions hidden in tRNA aminoacylation, the formation of peptide bonds, and the ending of translations, etc., we show our theoretical findings that the P and H correlations and affinity take vital roles in the protein synthesis process. We found the relationship between the 3' end ACCN sequences of tRNA molecules and the activated amino acids and its biological significance, the rRNAs' consensus sequences 5'NCC...TGG3' or 5'TGG...NCC3' which may perform as functional segments of rRNAs to help triggering the reaction of peptide formation, and common nature of releasing factors that the first amino acid residue of releasing factors ERF, RF1 and RF2 are all Methionine, except a few Alanine, which may be necessary for releasing the translated polypeptide and stopping the translating process. In the terms of P and H correlations and affinity, we provide explanations of why only using the poly (G) as mRNA template cannot get the poly (Gly) in experiments deciphering the genetic code, why Gly often appears in beta turns and why translational bypassing might occur when translating 5'GGAUGA on mRNA. Since amino acids and nucleotides are the subunits, respectively, for composing proteins and nucleic acids, these findings will help in further understanding interactions among the bio-macromolecules. These findings are also helpful for investigating rRNAs, further understanding the protein synthesis process and analysing similar bio-problems, and should be proved useful for experimental biologists.