Asthma and Risk of Stroke: A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have suggested that asthma is associated with an increased risk of stroke. However, the results are inconsistent. The aim of this study is to investigate the relation of asthma and the risk of stroke through a systematic review and meta-analysis of published research. METHODS: Pertinent studies were identified by a search of the PubMed and the Web of Science databases to June 2015. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed-effect or random-effect models when appropriate. Associations were tested in subgroups representing different participants and study characteristics. Publication bias was assessed with Egger's test. RESULTS: Five articles comprising 524,637 participants and 6031 stroke cases were eligible for inclusion. Asthma was associated significantly with increased risk of stroke, and the pooled HR was 1.32 (95% CI: 1.13, 1.54, I(2)=80.4%). Subgroup analyses revealed that the association between asthma and stroke risk was stronger among female patients (HR = 1.42, 95% CI: 1.15-1.76) and prospective cohort study design (HR = 1.52, 95% CI: 1.21-1.91). CONCLUSION: Asthma is associated with a significantly increased risk of stroke. This finding may have clinical and public health importance.

Fibrillar seeds alleviate amyloid-ß cytotoxicity by omitting formation of higher-molecular-weight oligomers.

Amyloid-ß (Aß) peptides can exist in distinct forms including monomers, oligomers and fibrils, consisting of increased numbers of monomeric units. Among these, Aß oligomers are implicated as the primary toxic species as pointed by multiple lines of evidence. It has been suggested that toxicity could be rendered by the soluble higher-molecular-weight (high-n) Aß oligomers. Yet, the most culpable form in the pathogenesis of Alzheimer's disease (AD) remains elusive. Moreover, the potential interaction among the insoluble fibrils that have been excluded from the responsible aggregates in AD development, Aß monomers and high-n oligomers is undetermined. Here, we report that insoluble Aß fibrillar seeds can interact with Aß monomers at the stoichiometry of 1:2 (namely, each Aß molecule of seed can bind to two Aß monomers at a time) facilitating the fibrillization by omitting the otherwise mandatory formation of the toxic high-n oligomers during the fibril maturation. As a result, the addition of exogenous Aß fibrillar seeds is seen to rescue neuronal cells from Aß cytotoxicity presumably exerted by high-n oligomers, suggesting an unexpected protective role of Aß fibrillar seeds.

A multi-functional peptide as an HIV-1 entry inhibitor based on self-concentration, recognition, and covalent attachment.

HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. The C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. A conserved salt bridge between Lys(574) in NHR and Asp(632) in CHR plays an essential role in the formation of the six-helix bundle. A multi-functional peptide inhibitor for anti-HIV derived from the CHR of gp41 has been designed. It bears a cholesterol group (Chol) at the C-terminal through which the inhibitor can anchor in the cell membrane, and carries an isothiocyanate (NCS) group at the side chain of Asp(632) through which the inhibitor can bind to target covalently at Lys(574) in NHR. The dual functionalized peptide (NCS-C34-Chol) shows high antiviral activity in vitro and in vivo. The inhibitor reacts specifically and rapidly to NHR from gp41. In addition, it exhibits better stability under the digestion of the Proteinase K than C34 and T20.

Exposure to bisphenol A and the development of asthma: A systematic review of cohort studies.

BACKGROUND: There is conflicting evidence about the association between bisphenol A (BPA) exposure and childhood asthma risk. We aimed to review the epidemiological literature on the relationship between prenatal or postnatal exposure to BPA and the risk of childhood asthma/wheeze. METHODS: The PubMed database was systematically searched, and additional studies were found by searching reference lists of relevant articles. RESULTS: Six studies fulfilled the eligibility criteria. Three studies found that prenatal BPA exposure is associated with an increased risk of childhood wheeze, while another study reported a reduced risk of wheeze. Regarding the postnatal BPA exposure, three studies demonstrated an increased risk of childhood asthma/wheeze. CONCLUSIONS: The mean prenatal BPA was associated with the risk of childhood wheeze/asthma. Besides, the influence of BPA exposure during the second trimester of pregnancy on the prevalence of childhood wheeze was marked. Further studies are urgently needed to explore the underlying mechanism about adverse effect of BPA exposure on childhood wheeze/asthma.

Rational design of an orthosteric regulator of hIAPP aggregation.

Developing compounds regulating amyloid toxic oligomer but not fibril formation should constitute an effective strategy for the treatment of diabetes. Based on the full understanding of the folding mechanism, we designed an orthosteric helix regulator that can promote hIAPP to assemble into large non-cytotoxic oligomers. As a result, the islet cells were protected.

Characterizing the assembly behaviors of human amylin: a perspective derived from C-terminal variants.

The differences in the C-terminal domains of human amylin peptide variants initiate different aggregation processes and differences in the composition of the aggregates by affecting the hydrophobic cores, conformations, and intra-sheet interactions of the peptides, which have distinct effects on the cytotoxicity of the peptides.

A covalently reactive group-modified peptide that specifically reacts with lysine16 in amyloid ß.

Lys16 is present in the core region of the amyloid ß (Aß) self-assembly in Alzheimer's disease. Here we report that the P9-NCS peptide can covalently react with Lys16 and inhibit Aß neurotoxic fibrillization. Moreover P9-NCS has high selectivity and it cannot react with amylin, insulin, fetal bovine serum, Q11 and MUC1 peptide.

Ectopic expression of macrophage scavenger receptor MARCO in synovial membrane-like interface tissue in aseptic loosening of total hip replacement implants.

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor with a very limited expression in healthy tissues. It was hypothesized that foreign body wear debris induces it to participate in handling of implant-derived particles in human synovial membrane-like tissue around aseptically loosening total hip replacement implants. A DNA microarray study showed that MARCO was upregulated in human monocytes by polymethyl methacrylate particles in cell culture. MARCO mRNA and protein were strongly expressed in numerous CD68 positive macrophages and foreign body giant cells in interface membrane lining and stroma around cemented implants, but was only present in a few cells in synovial membrane from osteoarthritis patients. A 65-kDa MARCO-reactive band was only found in interface tissue extracts. This is the first work to show upregulation of MARCO mRNA by foreign bodies in vitro. This is paralleled in vivo as MARCO mRNA and protein were over-expressed in chronic foreign body synovitis. As scavenger receptor MARCO apparently participates in handling of wear particles, which due to their nondegradable, irritating nature initiate/perpetuate foreign body inflammation, and peri-implant osteolysis.