[Detection of peripheral follicular helper T cells in rheumatoid arthritis].

OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4+CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4+CXCR5+Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5+Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4+CXCR5+Tfh cells were analyzed by flow cytometry. The transcript levels of B-cell lymphoma 6 (Bcl-6), as well as IL-21 and IL-21R, were measured by real-time polymerase chain reaction. Besides, serum IL-21 and CXCL13 concentrations were determined by enzyme-linked immunosorbent assay. The potential association between Tfh cells and RA disease activity was detected. RESULTS: The cell surface marker of CXCR5+ on CD4+ cells was significantly increasingly higher across the following groups versus HC: total RA patients (16.75±3.92 vs.7.49±1.84, P<0.001); RA patients with low disease activity or remission (16.62±3.43 vs. 7.49±1.84, P<0.001); RA patients with moderate disease activity (16.82±3.07 vs. 7.49±1.84, P<0.001) and RA patients with high disease activity (16.87±5.50 vs. 7.49±1.84, P<0.001). Besides, the percentages of ICOS+, PD-1+, IL-21R+ on CD4+CXCR5+Tfh cells in the RA patients were significantly higher than that of HC (ICOS+CD4+CXCR5+cells, 8.37±4.28 vs. 3.72±1.81, P<0.001; PD-1+CD4+CXCR5+cells, 1.57±1.10 vs. 0.24±0.30, P=0.035; IL-21R+CD4+CXCR5+ cells, 4.60 ±4.05 vs. 0.20±0.19, P=0.006). But the percentage of CD40L+ on CXCR5+CD4+Tfh cells in the RA patients was not significantly higher than that of HC (3.38±3.71 vs. 0.54±0.34, P=0.135). The IL-21R mRNA expression was elevated significantly (5.00±4.94 vs. 0.74±0.55, P<0.001) in the RA patients but not in Bcl-6 mRNA[4.54(3.33, 7.23) vs. 5.31(2.81, 7.44), P=0.329]or IL-21 mRAN[0.72(0.26, 3.45) vs. 0.56(0.27, 3.71), P=0.195]. Additionally, the serum interleukin-21 (IL-21) and CXCL13 levels in the RA patients were higher than in the healthy controls [IL-21, (200.49±154.56) ng/L vs. (8.21±5.95) ng/L, P<0.001; CXCL13, (93.72±49.72) ng/L vs. (43.09±1.28) ng/L, P<0.001] and were both positively correlated with RA disease activity indexes, including erythrocyte sedimentation rate, the disease activity score in 28 joints (ESR-based or CRP-based), clinical disease activity index, and simplified disease activity index. However, none of the Tfh cells, anti-citrullinated protein antibody or rheumatoid factor had any relationship with RA disease activity. CONCLUSION: Peripheral Tfh cells and their relevant cytokines are higher in RA patients than healthy controls, indicating Tfh cells may participate in the pathogenesis of RA, therefore, blocking the pathway of Tfh cells may be reasonable cellular targets for therapeutic intervention.

Exercise improves cardiac function and attenuates insulin resistance in Dahl salt-sensitive rats.

BACKGROUND: The development of heart failure (HF) secondary to hypertension is a complex process related to a series of physiological and molecular factors including glucose dysregulation. The overall objective of this study was to investigate whether exercise training could improve cardiac function and insulin resistance in a rat model of hypertensive HF. METHODS: Seven week old Dahl salt-sensitive rats received either 8% NaCl (n = 30) or 0.3% NaCl (n = 18) diet. After a 5-week diet, animals were randomly assigned to exercise training (treadmill running at 18 m/min, 5% inclination for 60 min, 5 days/week) or kept sedentary for 6 additional weeks. 2D echocardiography was used to calculate left ventricular (LV) dimensions, volumes and global functional parameters. LV global deformation parameters were measured with speckle tracking echocardiography. Insulin resistance was assessed using 1h oral glucose tolerance testing. RESULTS: High salt diet led to cardiac hypertrophy and HF, characterized by increased wall thicknesses and LV volumes as well as reduced deformation parameters. In addition, high salt diet was associated with the development of insulin resistance. Exercise training improved cardiac function, reduced the extent of interstitial fibrosis and reduced insulin levels 60 min post-glucose administration. CONCLUSIONS: Even if not fully reversed, exercise training in HF animals improved cardiac function and insulin resistance. Adjusted modalities of exercise training might offer new insights not only as a preventive strategy, but also as a treatment for HF patients.

Impact of 24 Weeks of Resistance and Endurance Exercise on Glucose Tolerance in Persons with Multiple Sclerosis.

BACKGROUND: Recently, the authors reported an elevated prevalence of impaired glucose tolerance in individuals with multiple sclerosis (MS), compared with matched healthy controls, indicating metabolic defects that may increase comorbidity. MS also leads to a more inactive lifestyle, increasing the likelihood to develop fat accumulation, muscle wasting/weakness, and exercise intolerance. In other populations, these health complications can partly be reversed by physical exercise. OBJECTIVE: The aim of this study was to determine the impact of a mild-to-moderate-intensity exercise program on glucose tolerance, ranging between normal and impaired, in persons with MS. DESIGN: Persons with MS (mean expanded disability status scale, 3.3 ± 0.2; mean age, 48 ± 15 yrs) were randomized to an exercise group (n = 29) or a nonexercise control group (n = 15). Glucose tolerance, as well as muscle strength, exercise tolerance, and body composition to validate the applied exercise program, was determined in both groups at baseline and after 6, 12, and 24 wks of mild-to-moderate-intensity combined endurance and resistance training. RESULTS: No effects on blood glucose and serum insulin were detected. However, 6 mos of exercise improved muscle strength, exercise tolerance, and lean tissue mass within the intervention group as compared with baseline. In the control group, no changes were detected. CONCLUSION: Twenty-four weeks of mild-to-moderate-intensity combined endurance and resistance training was not able to improve glycemic control in this cohort of persons with MS. Future research is warranted to investigate the influence of higher exercise intensities on glucose tolerance, in an attempt to remediate metabolic deficits and to decrease the prevalence of comorbidities in MS.

Exercise training improves insulin release during glucose tolerance testing in stable chronic heart failure patients.

PURPOSE: Chronic heart failure (CHF) patients often present with (pre)diabetes, which negatively influences prognosis. Unlike the proven effect of exercise on glucose regulation in the general population, its effect in CHF is unclear. Therefore, this study aimed at investigating the effect of exercise training on glucose regulation in stable CHF patients. METHODS: Twenty-two CHF patients were randomized into training (EX, n = 15) and control (CON, n = 7) groups. Before and after a 12-week training intervention involving endurance and resistance training, glucose tolerance (2-hour oral glucose tolerance test), exercise tolerance (cardiopulmonary exercise test), muscle strength (isokinetic dynamometer), heart function (echocardiography), glycated hemoglobin, body composition (dual-energy x-ray absorptiometry), and quality of life (EQ5D) were assessed. RESULTS: At baseline, glucose levels 2 hours after glucose intake were elevated in both groups. Whereas area under the glucose curve did not change, area under the insulin curve decreased following training (EX, -13 ± 23% vs CON, +22 ± 33%; P < .05). Changes in the ratio of mitral peak velocity of early filling/early diastolic mitral annular velocity and waist-to-hip fat mass ratio were related to changes in the insulin curve. Exercise training resulted in improved oxygen uptake at the second ventilatory threshold (EX, +10 ± 5% vs CON, -8 ± 5%; P < .05) and isokinetic strength endurance of the upper leg (EX, +25 ± 9% vs CON, -6 ± 5%; P < 0.05). Lean body tissue was increased by 2.2 ± 0.5% in EX versus 0.2 ± 0.6% in CON (P < .05). CONCLUSION: Our data suggest that exercise training attenuates worsening of glucose regulation typically seen in a stable CHF population.

Enhanced fluorescence from CdTe quantum dots self-assembled on the surface of silver nanoparticles.

This paper presents an investigation on the fluorescent properties of semiconductor CdTe quantum dots (QDs) self-assembled on the surface of PVP (polyvinylpyrrolidone)-capped silver nanoparticles (NPs) by the ligand field effect. A significant 2.5-fold enhancement in the integrated fluorescence intensities, red shift of fluorescence peak, and obvious decrease of lifetime were observed in the CdTe QDs assembled on the Ag NPs in comparison with the pure CdTe QDs. The fluorescence enhancement factor and red shift were found to depend on the Ag NP concentration. The fluorescence enhancement was attributed to a highly localized electromagnetic field on the Ag NPs generated by the surface plasma and the change in the surface trap state of the CdTe QDs originating from plasma oscillations in the Ag NPs. It is first proposed that the surface passivation of CdTe QDs is also an important factor for metal-enhanced fluorescence. The surface defects of CdTe QDs can be modified by the Cd-O coordination interaction between the CdTe QDs and PVP molecules, which will cause the trap state density and luminescence lifetime to decrease. The surface passivation of CdTe QDs can also improve fluorescence quantum yield and lead to the red shift of the fluorescence peak. Compared with previous reports, the occurrence of the self-assembly of CdTe QDs on the surface of PVP-capped Ag NPs is fairly simple and easy. From a practical point of view, the combination of CdTe QDs with Ag NPs may lead to the fluorescence enhancement, which could be utilized in a variety of chemical and biological detection applications.