Association between nuclear factor of activated T cells C2 polymorphisms and treatment response in rheumatoid arthritis patients receiving tumor necrosis factor-alpha inhibitors.

OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.

ADAM17 Genetic Variants and the Response of TNF-α Inhibitor in Rheumatoid Arthritis Patients.

PURPOSE: TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF­α results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNF­α inhibitors. PATIENTS AND METHODS: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-α inhibitors. RESULTS: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response. CONCLUSION: This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.

Oral diabetes medication and risk of dementia in elderly patients with type 2 diabetes.

AIM: To examine the effect of oral diabetes medication on the risk of dementia in an elderly cohort with type 2 diabetes. METHODS: This was a population-based cohort study using the Korean National Health Insurance claims data from 2002 to 2013. Elderly subjects (60 years of age or older) with and without type 2 diabetes were included; patients with new-onset type 2 diabetes were further divided into the oral diabetes medication group and no-medication group. RESULTS: Among 278,290 patients with type 2 diabetes, 56,587 developed dementia (20.3%) over 11 years of follow-up. Type 2 diabetes was associated with a 1.69-fold increased risk of dementia (95% CI 1.66-1.72). Among patients with newly diagnosed type 2 diabetes, the risk of dementia was lower in the oral diabetes medication group than in the no-medication group (adjusted hazard ratio [aHR], 0.79; 95% CI 0.77-0.81). Lower risk of dementia was particularly noticeable in all of the combination therapy groups and especially lower in the combination therapy group treated with dipeptidyl peptidase 4 inhibitor (aHR 0.48, 95% CI 0.45-0.51). CONCLUSION: Overall, the use of oral diabetes medication in type 2 diabetes patients significantly decreased the risk of dementia.

Effect of emulsification and spray-drying microencapsulation on the antilisterial activity of transcinnamaldehyde.

Spray-dried redispersible transcinnamaldehyde (TC)-in-water emulsions were prepared in order to preserve its antibacterial activity; 5% (w/w) TC emulsions were first obtained with a rotor-stator homogeniser in the presence of either soybean lecithin or sodium caseinate as emulsifiers. These emulsions were mixed with a 30% (w/w) maltodextrin solution before feeding a spray-dryer. The antibacterial activity of TC alone, TC emulsions with and without maltodextrin before and after spray-drying were assayed by monitoring the growth at 30 °C of Listeria innocua in their presence and in their absence (control). Whatever the emulsifier used, antilisterial activity of TC was increased following its emulsification. However, reconstituted spray-dried emulsions stabilised by sodium caseinate had a higher antibacterial activity suggesting that they better resisted to spray-drying. This was consistent with observation that microencapsulation efficiencies were 27.6% and 78.7% for emulsions stabilised by lecithin and sodium caseinate, respectively.

Effect of a Vietnamese Cinnamomum cassia essential oil and its major component trans-cinnamaldehyde on the cell viability, membrane integrity, membrane fluidity, and proton motive force of Listeria innocua.

The antibacterial mechanism of a Cinnamomum cassia essential oil from Vietnam and of its main component (trans-cinnamaldehyde, 90% (m/m) of C. cassia essential oil) against a Listeria innocua strain was investigated to estimate their potential for food preservation. In the presence of C. cassia essential oil or trans-cinnamaldehyde at their minimal bactericidal concentration (2700 µg·mL(-1)), L. innocua cells fluoresced green after staining with Syto9® and propidium iodide, as observed by epifluorescence microscopy, suggesting that the perturbation of membrane did not cause large pore formation and cell lysis but may have introduced the presence of viable but nonculturable bacteria. Moreover, the fluidity, potential, and intracellular pH of the cytoplasmic membrane were perturbed in the presence of the essential oil or trans-cinnamaldehyde. However, these membrane perturbations were less severe in the presence of trans-cinnamaldehyde than in the presence of multicomponent C. cassia essential oil. This indicates that in addition to trans-cinnamaldehyde, other minor C. cassia essential oil components play a major role in its antibacterial activity against L. innocua cells.