C1q/TNF-related protein 3 (CTRP3) and 9 (CTRP9) concentrations are decreased in patients with heart failure and are associated with increased morbidity and mortality.

BACKGROUND: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality. METHODS: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. CTRP3 and CTRP9 levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Both CTRP3 and CTRP9 concentrations were significantly decreased in the HFrEF group compared to the control group (p \u3c 0.001). Moreover, patients with higher New York Heart Association class had significantly lower CTRP3 or CTRP9 concentrations. Correlation analysis revealed that CTRP3 and CTRP9 levels were positively related with LVEF% (CTRP3, r = 0.556, p \u3c 0.001; CTRP9, r = 0.526, p \u3c 0.001) and negatively related with NT-proBNP levels (CTRP3, r = - 0.454, p \u3c 0.001; CTRP9, r = - 0.483, p \u3c 0.001). After a follow up for 36 months, after adjusted for age, LVEF and NT-proBNP, we observed that CTRP3 or CTRP9 levels below the 25th percentile was a predictor of total mortality (CTRP3,HR:1.93,95%CI1.03~3.62,P = 0.042;CTRP9,HR:1.98,95%CI:1.02~3.85,P = 0.044) and hospitalizations (CTRP3,HR:2.34,95% CI:1.43~3.82,P = 0.001;CTRP9,HR:2.67,95%CI:1.58~4.50,P \u3c 0.001). CONCLUSIONS: CTRP3 and CTRP9 are decreased in patients with HFrEF, proportionate to disease severity, and each is associated with increased morbidity and mortality. TRIAL REGISTRATION: NCT01372800 . Registered May 2011

Physical activity counseling in overweight and obese primary care patients: Outcomes of the VA-STRIDE randomized controlled trial.

The purpose of this 2-arm randomized clinical trial was to evaluate the effectiveness of a 12-month, expert system-based, print-delivered physical activity intervention in a primary care Veteran population in Pittsburgh, Pennsylvania. Participants were not excluded for many health conditions that typically are exclusionary criteria in physical activity trials. The primary outcome measures were physical activity reported using the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire and an accelerometer-based activity assessment at baseline, 6, and 12 months. Of the 232 Veterans enrolled in the study, 208 (89.7%) were retained at the 6-month follow-up and 203 (87.5%) were retained at 12 months. Compared to the attention control, intervention participants had significantly increased odds of meeting the U.S. recommended guideline of ≥ 150 min/week of at least moderate-intensity physical activity at 12 months for the modified CHAMPS (odds ratio [OR] = 2.86; 95% CI: 1.03-7.96; p = 0.04) but not at 6 months (OR = 1.54; 95% CI: 0.56-4.23; p = 0.40). Based on accelerometer data, intervention participants had significantly increased odds of meeting ≥ 150 min/week of moderate-equivalent physical activity at 6 months (OR = 6.26; 95% CI: 1.26-31.22; p = 0.03) and borderline significantly increased odds at 12 months (OR = 4.73; 95% CI: 0.98-22.76; p = 0.053). An expert system physical activity counseling intervention can increase or sustain the proportion of Veterans in primary care meeting current recommendations for moderate-intensity physical activity. Trial Registration Clinical trials.gov identifier: NCT00731094 URL: http://www.clinicaltrials.gov/ct2/show/NCT00731094

The Role of Long Non-coding RNAs in the Pathogenesis of RA, SLE, and SS

Rheumatoid diseases are a group of systemic autoimmune diseases which affect multiple organs with largely unknown etiology. In the past decade, long non-coding RNAs (lncRNAs) have emerged as important regulators of biological processes and contribute deeply to immune cell development and immune responses. Substantial evidences have been accumulated showing that LncRNAs involved in the pathogenesis of the rheumatoid diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). In this review, we summarize literature combined with bioinformatics methods to analyze the unique and common lncRNAs patterns in rheumatoid diseases and try to reveal the important function of lncRNAs in RA, SLE and SS

Effects of the stem extracts of Schisandra glaucescens Diels on collagen-induced arthritis in Balb/c mice

Ethnopharmacological relevance Schisandra glaucescens Diels (SGD) is used in a subclass of traditional Chinese medicine known as “Tujia drugs”. It has been long used for the treatment of rheumatoid arthritis (RA), cough with dyspnea, spontaneous sweating, night sweating, chronic diarrhea, and neurasthenia. As a woody liana growing in mountain jungles at the altitudes of 750–1800 m, it is mainly distributed in Sichuan and Hubei Provinces of China. Aim of the study To evaluate the antiarthritic activity of acetate (EA) and n-butanol (Bu) fractions of SGD extract on a collagen-induced arthritis mice model. Materials and methods Acute toxicity of EA and Bu fractions of SGD extract was evaluated by gavage on normal mice. Pharmacological investigations were conducted on arthritis male Balb/c mice. The animal model was induced by immunization with type II bovine collagen (CII) on the 1st and the 14th day of the experimental schedule. EA fraction (104, 312, 936 mg/kg), Bu fraction (156, 469, 1407 mg/kg) of SGD extract was orally administered every two days since the 15th day for 3 weeks. Progression of edema in the paws was measured using a vernier caliper every 3 days since the 10th day. At the end of the experiment, the spleen index and histological changes of the hind knee joints were investigated. Additionally, to explore the possible antirheumatic mechanisms of the EA and Bu fractions, ELISA was carried out to analyze TNF-α, IL-10, IL-6 and IL-1β in the serum. Results The half lethal doses of both EA and Bu fractions were much higher than the dose administered in the pharmacological investigations. Oral administration of EA fraction and Bu fraction of SGD extract significantly and does-dependently inhibited type ІІ collagen induced arthritis (CIA) in mice, as indicated by the effects on paws swelling and spleen index. Histopathological examinations demonstrated that SGD effectively protected the bones and cartilages of knee joints from erosion, lesion and deformation. Besides, the serum concentrations of cytokines TNF-α, IL-1β and IL-6 were significantly lower than the ones from the vehicle control group. Respectively, while cytokine IL-10 was remarkably higher compare with the vehicle control group. Conclusions SGD might be a safe and effective candidate for the treatment of RA, and deserves further investigation on the chemical components in both EA and Bu fractions of SGD extract

Probing Allostery through DNA

Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which—together with molecular dynamics simulations—suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.Chemistry and Chemical Biolog