Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment / 中华医学杂志(英文版)

<p><b>Objective</b>Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions.</p><p><b>Data Sources</b>Using the combined keywords: "RBD", "neurodegenerative disease", "Parkinson disease", and "magnetic resonance imaging", the PubMed/MEDLINE literature search was conducted up to January 1, 2018.</p><p><b>Study Selection</b>A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full.</p><p><b>Results</b>Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings.</p><p><b>Conclusions</b>More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.</p>

Bergapten attenuates D-galactose-induced immunosenescence in BALB/c mice / 中国药理学与毒理学杂志

OBJECTIVE Bergapten (BG), is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg-1)subcutaneous injections for 30 d.To evaluate the establishment of the aging-related effect in mice, serum samples of BALB/c mice were collected from tail vein. Aging BALB/c mice were freely divided into three groups: negative control group received 1% Tween 80 solution only, named D-gal group. Positive groups were received BG administration at the dose of 20 and 100 mg·kg-1, named D-gal+BG(20)group and D-gal+BG(100)group,respectively.Effects of bergapten on T lympho-cyte proliferation and flow cytometry were assessed by using the splenic cell suspension. Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ)and interleukin-4(IL-4) levels of the isolated serum. Immunophenotype was determined by using mixture of antibodies includ-ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg-1)therapy can modulate immu-nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat-ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1)and T helper 2(Th2)cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg-1)restored antigen-specific CD4+and CD8+T cells in aging models (P<0.05, P<0.01), which may help to curing chronic infections. CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.

Myeloid-derived suppressor cells promoted autologous B cell proliferation in rheumatoid arthritis / 北京大学学报(医学版)

Objective:To investigate the effect of myeloid-derived suppressor cells (MDSC) on pro liferation of B lymphocytes in rheumatoid arthritis (RA) patients.Methods:The peripheral blood specimens were collected from 15 healthy adults and 38 RA patients who were divided into high disease activity group,medium activity group and low activity group according to their 28-joint disease activity score (DAS28).And the frequencies of MDSC were determined by flow cytometry.Then,B cells and MDSC were isolated by flow cytometry,respectively.B cells were labeled with carboxyfluorescein diacetate suecinimidyl ester (CFSE) and then were co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L CpG,for 3 days.Flow cytometry was performed to investigate the proliferation of B cells.Results:MDSC expanded markedly in high disease activity patients (7.13％ ±2.17％) compared with medium (5.35％ ±-1.36％) and low disease activity patients (4.72％ ± 1.08％) or healthy controls (4.79％ ± 1.02％) (P ＜ 0.05),and there were no statistical differences between healthy controls,medium and low disease activity RA (P ＞ 0.05).Moreover,the frequencies of MDSC were positively correlated with the DAS28 (P ＜ 0.05).After co-culture,MDSC significantly promoted B cell proliferation (P ＜0.01).Conclusion:Our studies showed that MDSC expanded obviously in high disease activity RA patients,and their frequencies were positively correlated with the disease activities.Furthermore,MDSC could promote autologous B cell proliferation remarkably in vitro.These findings suggest that MDSC might be involved in RA pathogenesis through regulating B cell functions.

Increased serum C-C chemokine ligand 19 levels correlated with B cell abnormalities in systemic lupus erythematosus / 北京大学学报(医学版)

Objective:To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters,trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus.Methods:The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls.These SLE patients included 75 patients who received treatment with glucocorticoids and disease-modifying anti-rheumatic drug (DMARD) and 15 patients without therapy.The frequencies of peripheral blood B cells and the B cell subsets were assessed in the patients with SLE by flow cytometry.The correlation between the clinical data,laboratory parameters,B cell subset frequencies and serum CCL19 levels were analyzed.Independent samples t test,paired t test,Pearson and Spearman correlation were used for statistical analyses.Results:The levels of CCL19 were markedly higher in the SLE patients without therapy and the patients with therapy than in the health controls[(596.25 ±409.19) ng/L and (422.90 ± 395.84) ng/L vs.157.79 ± 125.23) ng/L,all P ＜ 0.001].Serum CCL19 levels in the SLE patients without therapy were higher than the SLE patients who accepted glucocorticoids and DMARD treatment (P ＜ 0.05).The levels of serum CCL19 were positively correlated with anti-double stranded deoxyribonucleic acid (dsDNA),anti-nucleosome antibody (AnuA),IgA,IgG and IgM (r =0.38,P =0.007;r =0.332,P =0.029;r =0.519,P =0.007;r =0.461,P =0.018,respectively).Serum CCL19 levels in the SLE patients with photosensitivity,arthritis and secondary Sj(o)gren's syndrome were higher than the SLE patients without photosensitivity,arthritis and secondary Sj(o)gren's syndrome,respectively [(562.25 ± 399.12) ng/L,(565.6 ± 435.24) ng/L and (694.9 ± 531.02) ng/L vs.(394.7 ± 281.42) ng/L,(385.90-± 325.33) ng/L and (424.8 ± 305.46) ng/L,all P ＜ 0.05].The levels of serum CCL19 were positively correlated with the percentage of CD27-B cells and CD27-IgD-double-negative memory B cells (r =0.519,P =0.007;r =0.461,P =0.018,respectively).However,the levels of serum CCL19 were negatively correlated with the percentage of CD27 + memory B cells and CD27 + IgD-switched memory B cells (r =-0.433,P =0.027;r =-0.616,P =0.001,respectively).Conclusion:The increased serum CCL19 levels in SLE patients were associated with the production of autoantibodies,and CCL19 might be involved in the pathogenesis of SLE by disturbing the homeostasis of B cell subsets.