3,184 research outputs found

    Role of NLRP3 in the pathogenesis and treatment of gout arthritis

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    Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA

    Mechanical Character of Typica1 Plant Leaf Surfaces

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    The hardness of typical plant leaves surfaces was investigated and analyzed by nano-hardness tester. Results show that the mechanical character of varied texture and varied surface morphologies shows regularity. The hardness of coriaceous fresh leaves (Bambusa phyllostachys pubescens etc.) and ligneous leaves is great. Waxiness leaves′ hardness (such as Nelumbo nucifera Gaertn, Canna indica Linn (generalis) is little. The hardness of convex morphology part is better than that of concave morphology part on non-smooth morphology leaf surfaces. And that the hardness of surface layer is better than that of internal layer in the same leaf. This study may be important biological foundation for design and fabrication of bionic engineering surface and composite materials. Key words: engineering bionic; plant leaf; hardness; mechanical characte

    A Novel Mutation in CRYBB1 Associated with Congenital Cataract-Microcornea Syndrome: The p.Ser129Arg Mutation Destabilizes the βB1/βA3-crystallin Heteromer But Not the βB1-crystallin Homomer

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    Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [θ]=0.0), which closely flanks the â-crystallin gene cluster locus. Direct sequencing of the candidate âB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant β-crystallins revealed that the mutation impaired the structures of both βB1-crystallin homomer and βB1/βA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of βB1/βA3-crystallin but not βB1-crystallin. These findings highlight the importance of protein-protein interactions among β-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC. © 2011 Wiley-Liss, Inc

    Comparative genome analysis of plant ascomycete fungal pathogens with different lifestyles reveals distinctive virulence strategies

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    Background: Pathogens have evolved diverse lifestyles and adopted pivotal new roles in both natural ecosystems and human environments. However, the molecular mechanisms underlying their adaptation to new lifestyles are obscure. Comparative genomics was adopted to determine distinct strategies of plant ascomycete fungal pathogens with different lifestyles and to elucidate their distinctive virulence strategies. Results: We found that plant ascomycete biotrophs exhibited lower gene gain and loss events and loss of CAZyme-encoding genes involved in plant cell wall degradation and biosynthesis gene clusters for the production of secondary metabolites in the genome. Comparison with the candidate effectome detected distinctive variations between plant biotrophic pathogens and other groups (including human, necrotrophic and hemibiotrophic pathogens). The results revealed the biotroph-specific and lifestyle-conserved candidate effector families. These data have been configured in web-based genome browser applications for public display (http://lab.malab.cn/soft/PFPG). This resource allows researchers to profile the genome, proteome, secretome and effectome of plant fungal pathogens. Conclusions: Our findings demonstrated different genome evolution strategies of plant fungal pathogens with different lifestyles and explored their lifestyle-conserved and specific candidate effectors. It will provide a new basis for discovering the novel effectors and their pathogenic mechanisms
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