Objective Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-jB (NF-jB) subunit and interleukin-1b (IL-1b), and inflammatory cytokine profiles in women with preeclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.Design and method A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1b, NF-jB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-a [TNF-a], interferon-c [IFN-c] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.Setting A single tertiary maternity hospital in Vancouver, Canada.Population Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia ( ‡34 +0 weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.Results Women with pre-eclampsia (as a single combined group of early-and late-onset, and particularly in women with earlyonset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-jB subunit, and IL-1b mRNA expression, and TNF-a:IL-10 and IL-6:IL-10 ratios compared with other groups.Conclusions These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

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CMV infection seems to affect the occurrence of pre-eclampsia. Evaluation of the relation between CMV infection and pre-eclampsia may provide mechanistic insights into pre-eclampsia-related inflammation.

Lightweight nitrogen-doped ordered mesoporous carbon (NOMC) with high specific surface area and pore volume have been prepared through self-assembly and subsequent heat treatment route. The spherical NOMC particles are decorated with CoFe2O4 nanoparticles via coprecipitation method to enhance their microwave absorption property. The electromagnetic parameters of the NOMC and CoFe2O4/NOMC composites are measured and the microwave reflection loss properties are evaluated in the frequency range of 0.5–18 GHz. The results show that both the real part and imaginary part of permittivity of NOMC totally decline and the real part of permeability increases with the introduction of ferrite. However, the negative values of the imaginary part of the complex permeability appear for the CoFe2O4/NOMC composites, which may be caused by enhanced eddy current effect due to the introduction of ferrite. The reflection loss results exhibit that the CoFe2O4/NOMC composites have excellent microwave absorption performances. The absorption bandwidth less than −10 dB reaches 5.0 GHz (11.9–16.9 GHz) for 40-F/NOMC composite (40 wt % ferrite) with 1.5 mm of thickness and the minimum reflection loss value is up to −38.3 dB at 3.9 GHz for 30-F/NOMC composite with 4.0 mm of thickness. The excellent absorption properties derive from the synergistic effect between dielectric loss of NOMC and magnetic loss of ferrite and better impendence matching at air and ferrite/NOMC composite interface. Thus, the lightweight ferrite/NOMC composites exhibit their great potential as microwave absorbing materials.

Ubenimex is a low-molecular-weight dipeptide with the ability to inhibit aminopeptidase N (APN) activity, enhance the function of immunocompetent cells and confer antitumor effects. We sought to characterize the effects of ubenimex on renal cell carcinoma (RCC). The 786-O and OS-RC-2 human RCC cell lines were positive for APN expression and ubenimex decreased APN activity without affecting the expression. Ubenimex suppressed the proliferation of both cell lines in a concentration‑dependent manner, as assessed by curve growth analysis and WST-8 proliferation assay. Wound healing and Matrigel invasion assays demonstrated that the migration and invasion of the RCC cells were also markedly suppressed by ubenimex. Furthermore, ubenimex increased the mortality of both RCC cell lines as determined by the LDH cytotoxicity assay. This affect was accompanied by increased levels of LC3B with no apparent effect on Caspase3; and we observed that autophagy increased significantly after ubenimex treatment in both RCC cell lines by electron microscopy. Moreover, rapamycin enhanced the cytotoxic effect of ubenimex, while 3-methyladenine reversed the effect, indicating that ubenimex cytotoxicity occured through an autophagy-related mechanism. To further assess the potential applicability of ubenimex in the treatment of RCC, we performed immunohistochemistry using tissue microarrays representing 76 RCC patients that underwent radical nephrectomy. The results showed that APN was expressed in most, but not all of the RCC tissues and that the expression was reduced in RCC as compared to the normal kidney tissues, suggesting a potential role for APN in RCC development. Collectively, these results indicated that ubenimex inhibits proliferation, migration and invasion of RCC cells. Ubenimex may induce autophagy, which may be associated with its effect on the growth arrest and the cell death of RCC cells.

Papillomaviruses are small, double-stranded DNA viruses that encode the E2 protein, which controls transcription, replication, and genome maintenance in infected cells. Posttranslational modifications (PTMs) affecting E2 function and stability have been demonstrated for multiple types of papillomaviruses. Here we describe the first phosphorylation event involving a conserved tyrosine (Y) in the bovine papillomavirus 1 (BPV-1) E2 protein at amino acid 102. While its phosphodeficient phenylalanine (F) mutant activated both transcription and replication in luciferase reporter assays, a mutant that may act as a phosphomimetic, with a Y102-toglutamate (E) mutation, lost both activities. The E2 Y102F protein interacted with cellular E2-binding factors and the viral helicase E1; however, in contrast, the Y102E mutant associated with only a subset and was unable to bind to E1. While the Y102F mutant fully supported transient viral DNA replication, BPV genomes encoding this mutation as well as Y102E were not maintained as stable episomes in murine C127 cells. These data imply that phosphorylation at Y102 disrupts the helical fold of the N-terminal region of E2 and its interaction with key cellular and viral proteins. We hypothesize that the resulting inhibition of viral transcription and replication in basal epithelial cells prevents the development of a lytic infection.IMPORTANCE Papillomaviruses (PVs) are small, double-stranded DNA viruses that are responsible for cervical, oropharyngeal, and various genitourinary cancers. Although vaccines against the major oncogenic human PVs are available, there is no effective treatment for existing infections. One approach to better understand the viral replicative cycle, and potential therapies to target it, is to examine the posttranslational modification of viral proteins and its effect on function. Here we have discovered that the bovine papillomavirus 1 (BPV-1) transcription and replication regulator E2 is phosphorylated at residue Y102. While a phosphodeficient mutant at this site was fully functional, a phosphomimetic mutant displayed impaired transcription and replication activity as well as a lack of an association with certain E2-binding proteins. This study highlights the influence of posttranslational modifications on viral protein function and provides additional insight into the complex interplay between papillomaviruses and their hosts.

Systemic inflammation and abnormal/poor placentation represent hallmarks of pre-eclampsia. Accumulating evidence suggests that infectious agents might increase the risk of pre-eclampsia; the innate immune defense mechanisms may interact with pro-inflammatory pathways, and contribute to the development of pre-eclampsia. The evidence for this has been supported by indirect epidemiologic and clinical studies, as well as by some direct support from experimental studies. Recent data directly implicate signaling by Toll-like receptors in the pathogenesis of pre-eclampsia, and establish a crucial link between pre-eclampsia and defense against both foreign pathogens and endogenously generated inflammatory ligands. Here, we review the rapid progress in this field, which has improved our understanding of the interplay between pathogen invasion, innate immune defense mechanisms, and pre-eclampsia.