Pseudomonas aeruginosa (PA)-induced keratitis is one of the most common and destructive bacterial diseases. The pathogenesis of PA infections is closely associated with excessive inflammatory responses. Nucleotide oligomerization domain (NOD)-like receptor (NLR) family with caspase activation and recruitment domain (CARD) containing 3 (NLRC3) protein has been implicated as a negative regulator of inflammation and antiviral response, but the role of NLRC3 in PA-induced keratitis has not been described. In the present study, we investigated the effects of NLRC3 in PA-induced keratitis and explored the underlying mechanism. We found that the expression of NLRC3 was decreased in mouse corneas and macrophages after PA infection. Overexpr-ession of NLRC3 significantly attenuated disease progression, inhibited the activation of nuclear factor-κB signaling and decreased the production of pro-inflammatory cytokines after PA infection. Furthermore, overexpression of NLRC3 promoted K48-linked polyubiquitination and degradation of interleukin-1 receptor-associated kinase 1 (IRAK1). Taken together, we demonstrated that NLRC3 has an anti-inflammatory effect on PA-induced keratitis, which may provide an improved understanding of host resistance to PA infection.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factor β-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.

CSLTMs showed a thickness-dependent cytotoxic efficacy of DOX and greater drug resistance than the control, thereby providing useful information toward the development of improved biomimetic tumor models.

To investigate the effects of matrix metalloproteinase-1 (MMP-1) gene polymorphisms on the onset of osteomyelitis in Chinese Han population.In all, 80 osteomyelitis patients (case group) and 81 healthy people (control group) were recruited into this case-control study. Polymerase chain reaction-restriction fragment length polymorphism method was utilized to examine the genotypes of MMP-1 polymorphisms (−1607 2G/1G and −519A/G) in the 2 groups. Genotype and allele differences between the case and control groups were analyzed by chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to present the association strength between MMP-1 gene polymorphisms and osteomyelitis.Frequencies of −1607 2G/2G genotype between the case and control groups were statistically significant (P = .025). Compared with 1G/1G genotype carriers, the 2G/2G genotype carriers had 1.605 times risk of developing osteomyelitis (OR 2.605, 95% CI 1.116–6.082). Meanwhile, the 2G allele significantly associated with the risk of osteomyelitis (OR 1.735, 95% CI 1.115–2.701). In addition, frequency of −519GG genotype was obviously higher in case group than that in control group (P = .024), and GG genotype related to an increased risk of osteomyelitis (OR 2.792, 95% CI 1.127–6.917). Whereas, the −519G allele may be a susceptible factor for osteomyelitis (OR 1.622, 95% CI 1.038–2.536).The MMP-1 −1607 (2G/1G) and −519 (A/G) polymorphisms may contribute to the onset of osteomyelitis.