Surfactant proteins (SP) are involved in surfactant function and innate immunity in the human lung. Both lung function and innate immunity are altered in CF, and altered SP levels and genetic association are observed in Cystic Fibrosis (CF). We hypothesized that single nucleotide polymorphisms (SNPs) within the SP genes associate with CF or severity subgroups, either through single SNP or via SNP-SNP interactions between two SNPs of a given gene (intragenic) and/or between two genes (intergenic). We genotyped a total of 17 SP SNPs from 72 case-trio pedigree (SFTPA1 (5), SFTPA2 (4), SFTPB (4), SFTPC (2), and SFTPD (2)), and identified SP SNP associations by applying quantitative genetic principles. The results showed (a) Two SNPs, SFTPB rs7316 (p = 0.0083) and SFTPC rs1124 (p = 0.0154), each associated with CF. (b) Three intragenic SNP-SNP interactions, SFTPB (rs2077079, rs3024798), and SFTPA1 (rs1136451, rs1059057 and rs4253527), associated with CF. (c) A total of 34 intergenic SNP-SNP interactions among the 4 SP genes to be associated with CF. (d) No SNP-SNP interaction was observed between SFTPA1 or SFTPA2 and SFTPD. (e) Equal number of SNP-SNP interactions were observed between SFTPB and SFTPA1/SFTPA2 (n = 7) and SP-B and SFTPD (n = 7). (f) SFTPC exhibited significant SNP-SNP interactions with SFTPA1/SFTPA2 (n = 11), SFTPB (n = 4) and SFTPD (n = 3). (g) A single SFTPB SNP was associated with mild CF after Bonferroni correction, and several intergenic interactions that are associated (p < 0.01) with either mild or moderate/severe CF were observed. These collectively indicate that complex SNP-SNP interactions of the SP genes may contribute to the pulmonary disease in CF patients. We speculate that SPs may serve as modifiers for the varied progression of pulmonary disease in CF and/or its severity.

Summary In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σM, σW, and σX all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge-region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σM to nisin resistance is expression of ltaSa, encoding a stress-activated lipoteichoic acid synthase, and σX functions primarily by activation of the dlt operon controlling D-alanylation of teichoic acids. Together, σM and σX regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σW is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σW contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homolog), and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin, and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis.

Gestational diabetes mellitus (GdM) is a type of diabetes mellitus (dM) that occurs during pregnancy. The present study aimed to investigate the roles of microrna (mir)-195-5p and enhancer of zeste homolog 2 (eZH2) in GdM, and their potential association. Human umbilical vein endothelial cells (HuVecs) were collected from healthy and GdM umbilical cords, and the endothelial properties were detected by flow cytometry. mRNA expression levels of miR-195-5p and EZH2, and EZH2 protein expression levels were detected by reverse transcription-quantitative Pcr (rT-qPcr) and western blot analysis, respectively. cell colony formation and flow cytometry were performed to determine cell proliferation and apoptosis. Furthermore, the target gene of mir-195-5p was predicted and assessed using a dual-luciferase reporter assay. The levels of cell viability, proliferation and apoptosis following the overexpression of miR-195-5p, EZH2 or mir-195-5p + eZH2, were detected using cell counting Kit-8, colony formation and flow cytometry assays, respectively. In addition, the mRNA expression levels of miR-195-59 and EZH2, and EZH2 protein expression levels following transfection with overexpression plasmids were detected using rT-qPcr and western blot analysis, respectively. it was identified that high mRNA expression of miR-195-5p, and low EZH2 mRNA and protein expression levels decreased the level of cell proliferation and the high apoptotic rate of GdM-HuVecs. in addition, mir-195-5p was predicted and identified to target EZH2, and miR-195-5p overexpression was identified to inhibit cell proliferation and promote apoptosis. However, it was demonstrated that upregulation of eZH2 could alleviate the inhibition of cell proliferation and the increased apoptotic rate induced by miR-195-5p overexpression. Therefore, the present results suggested that mir-195-5p may inhibit cell viability, proliferation and promote apoptosis by targeting eZH2 in GdM-induced HuVecs.

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