Streptococcus thermophilus extends lifespan through activation of DAF-16-mediated antioxidant pathway in Caenorhabditis elegans

Streptococcus thermophilus bacteria, which are widely used as fermented starter for dairy production, exert various beneficial health effects. Nevertheless, even though pro-longevity effects of various probiotics have been reported, no report has described Streptococcus thermophilus effects on longevity. This study was conducted to evaluate Streptococcus thermophilus effects on lifespan extension and to elucidate the Streptococcus thermophilus-mediated longevity mechanism using Caenorhabditis elegans worms as a model animal. They were fed standard food (Escherichia coli OP50) or Streptococcus thermophilus from the young adult stage. Feeding with Streptococcus thermophilus, compared to Escherichia coli OP50, to Caenorhabditis elegans extend the lifespan, reduced lipofuscin accumulation, and maintain vigorous locomotion. Feeding with Streptococcus thermophilus did not alter the worm growth curve or the offspring number, indicating that the Streptococcus thermophilus-mediated lifespan extension is not attributable to caloric restriction. The qRT-PCR data showed that Streptococcus thermophilus increased the expression of daf-16 and some of its downstream antioxidant genes. Furthermore, the pro-longevity effects of Streptococcus thermophilus were decreased in loss-of-function mutant of daf-16. Results show that Streptococcus thermophilus extends the lifespan of Caenorhabditis elegans through DAF-16-mediated antioxidant pathway activation.     

Functional and oncological outcomes after retropharyngeal node dissection for papillary thyroid carcinoma

European Archives of Oto-Rhino-Laryngology - Papillary thyroid carcinoma frequently metastasizes to central and lateral neck lymph nodes, but metastasis to retropharyngeal lymph nodes (RPLN) is...     

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.     

Scaffold-Mediated Sustained,Non-viral Delivery of miR-219/miR-338 Promotes CNS Remyelination

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Preparation,Characterization, Solubility,and Antioxidant Capacity of Ellagic Acid-Urea Complex

Ellagic acid (EA), a natural polyphenol found in berries, has high antioxidant capacity. This study aimed to improve EA solubility by complex formation with urea (UR) using solvent evaporation method and evaluate its solubility, antioxidant capacity, and physical properties. The solubility test (25 °C, 72 h) showed that the solubility of EVP (EA/UR = 1/1) was approximately two-fold higher than that of EA (7.13 µg/mL versus 3.99 µg/mL). Moreover, the IC₅₀ values of EA and EVP (EA/UR = 1/1) (1.50 µg/mL and 1.30 µg/mL, respectively) showed higher antioxidant capacity of EVP than that of EA. DSC analysis revealed that the UR peak at 134 °C disappeared, and a new endothermic peak was observed at approximately 250 °C for EVP (EA/UR = 1/1). PXRD measurements showed that the characteristic peaks of EA at 2θ = 12.0° and 28.0° and of UR at 2θ = 22.0°, 24.3°, and 29.1° disappeared and that new peaks were identified at 2θ = 10.6°, 18.7°, and 26.8° for EVP (EA/UR = 1/1). According to 2D NOESY NMR spectroscopy, cross-peaks were observed between the -NH and -OH groups, suggesting intermolecular interactions between EA and UR. Therefore, complexation was confirmed in EA/UR = 1/1 prepared by solvent evaporation, suggesting that it contributed to the improvement in solubility and antioxidant capacity of EA.     

Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.

BACKGROUND: DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts. METHODS: We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing. RESULTS: The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+ 1587G>A, p = .014; 396T   

Discontinuation of etanercept after achievement of sustained remission in patients with rheumatoid arthritis who initially had moderate disease activity—results from the ENCOURAGE study,a prospective,international, multicenter randomized study

Objectives: To investigate the efficacy and safety of etanercept (ETN) in patients with rheumatoid arthritis (RA) with moderate disease activity and the possibility to discontinue ETN after achieving remission.

Methods: Multicenter, randomized, and open-label study was conducted in Japan and Korea. RA patients (disease duration?<5 years) with moderate disease activity despite methotrexate (MTX) treatment were allocated to either MTX or ETN?+?MTX (Period 1) for 12 months. Patients who achieved sustained remission defined as DAS28?<?2.6 at both 6 and 12 months in the ETN?+?MTX group, were randomized to either continue or discontinue ETN for 12 months (Period 2).

Results: A total of 222 patients were enrolled in Period 1 and clinical remission was achieved in 106/157 (67.5%) and 5/28 (17.9%) patients in the ETN?+?MTX and MTX groups, respectively. In Period 2, sixty-seven patients were randomized and finally 28/32 (87.5%) and 15/28 (53.6%) patients who continued or discontinued ETN maintained clinical remission. Baseline disease activity and the presence of comorbid diseases influenced the maintenance of remission after ETN discontinuation.

Conclusions: ETN?+?MTX was efficient for RA patients with moderate disease activity into remission. After achieving sustained remission, a half of the patients who discontinued ETN could maintain remission for 1 year.     

Improvement of physical activity in chronic obstructive pulmonary disease by pulmonary rehabilitation and pharmacological treatment

Physical activity (PA) is defined as bodily movement produced by skeletal muscles with energy expenditure beyond resting levels. PA is closely related to reduced morbidity and mortality in chronic obstructive pulmonary disease (COPD). Self-report questionnaires are often subject to recall bias, correlating poorly with objectively qualified PA, and do not provide an accurate estimate of free-living energy expenditure. PA may be objectively evaluated by newly developed tri-axial accelerometers by quantifying steps or body movements over a period of time. Low-intensity, home-based pulmonary rehabilitation (PR) using pedometer feedback improves PA. Improvement in physiological factors correlates with increased walking time in stable elderly COPD patients.This review focuses on the effects of PR and pharmacological treatment on PA in COPD patients. We selected 32 studies from our literature search evaluating the effects of PR and 11 studies examining the effects of pharmacological treatment on PA. Findings in both categories were inconsistent. Nineteen studies showed a positive effect with PR whereas 13 showed no effect. Eight studies showed a positive effect, while three revealed no effect from pharmacological intervention. As both interventions increase exercise capacity without a consistent effect on PA, counseling with behavioral changes may be necessary to achieve a significant and lasting increase in PA. Changing PA behavior in COPD patients requires an interdisciplinary approach involving specialists in respiratory medicine, rehabilitation, social, and behavioral sciences. Future research in this area is warranted to advance our knowledge in this area, specifically with regard to the interaction of pharmacological and non-pharmacological interventions.     

Analysis of systemic and airway inflammation in obstructive sleep apnea

Purpose

The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA.

Methods

This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry.

Results

In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum.

Conclusions

Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.