Adipocytokines and CD34+ Progenitor Cells in Alzheimer's Disease

BACKGROUND: Alzheimer's disease (AD) and atherosclerosis share common vascular risk factors such as arterial hypertension and hypercholesterolemia. Adipocytokines and CD34(+) progenitor cells are associated with the progression and prognosis of atherosclerotic diseases. Their role in AD is not adequately elucidated. METHODS AND FINDINGS: In the present study, we measured in 41 patients with early AD and 37 age- and weight-matched healthy controls blood concentrations of adiponectin and leptin by enzyme linked immunoabsorbent assay and of CD34(+) progenitor cells using flow cytometry. We found significantly lower plasma levels of leptin in AD patients compared with the controls, whereas plasma levels of adiponectin did not show any significant differences (AD vs. control (mean ± SD): leptin:8.9 ± 5.6 ng/mL vs.16.3 ± 15.5 ng/mL;P = 0.038; adiponectin:18.5 ± 18.1 µg/mL vs.16.7 ± 8.9 µg/mL;P = 0.641). In contrast, circulating CD34(+) cells were significantly upregulated in AD patients (mean absolute cell count ± SD:253 ± 51 vs. 203 ± 37; P = 0.02) and showed an inverse correlation with plasma levels of leptin (r =  -0.248; P = 0.037). In logistic regression analysis, decreased leptin concentration (P = 0.021) and increased number of CD34(+) cells (P = 0.036) were both significantly associated with the presence of AD. According to multifactorial analysis of covariance, leptin serum levels were a significant independent predictor for the number of CD34(+) cells (P = 0.002). CONCLUSIONS: Our findings suggest that low plasma levels of leptin and increased numbers of CD34(+) progenitor cells are both associated with AD. In addition, the results of our study provide first evidence that increased leptin plasma levels are associated with a reduced number of CD34(+) progenitor cells in AD patients. These findings point towards a combined involvement of leptin and CD34(+) progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin and circulating CD34(+) progenitor cells could represent an important molecular link between atherosclerotic diseases and AD. Further studies should clarify the pathophysiological role of both adipocytokines and progenitor cells in AD and possible diagnostic and therapeutic applications

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients

Objectives: BCL3, a known atypical IκB family member, has been documented to be upregulated in hematological malignancies and in some solid tumors, functioning as a crucial player in tumor development. Recently, rs8100239, a tag-Single Nucleotide Polymorphism (SNP) in BCL3 (T > A) has been identified, but there are no data regarding its involvement in non-small-cell lung cancer (NSCLC) initiation and progression. Materials and methods: To study the possible association of BCL3 with NSCLC, 268 patients and 279 healthy controls were genotyped for rs8100239. Moreover, BCL3 protein expression was also investigated in 112 NSCLC cases through an immunohistochemical analysis. Results: NSCLC patients with AA genotype displayed significantly worse prognosis compared to T allele carriers (P < 0.001), who had less frequent intermediate nuclear BCL3 expression (P = 0.042). In addition, overexpression of BCL3 was detected in tumor specimens, compared to normal tissue (P < 0.001). Furthermore, BCL3 protein levels were associated with five-year survival (P=0.039), maximum diameter of lesion (P = 0.012), grade (P = 0.002) and relapse frequency (P = 0.041). Conclusions: The present study is the first to show a relationship between the genetic variation rs8100239 of BCL3 and cancer patients' survival. It also represents the first quantitative evaluation of BCL3 expression in NSCLC. Our findings indicate that rs8100239 may be considered as a novel prognostic indicator, demonstrating also the overexpression of BCL3 protein in NSCLC and implicating this pivotal molecule in the pathogenesis of NSCLC. © 2015 Elsevier Ireland Ltd

Association of IL‐10

Abstract Background Previous studies have generated controversial results about the association of interleukin 10 (IL‐10) gene polymorphisms (−1082G/A) in the progression of cardiovascular disease (CVD). Therefore, this study processed a systemic meta‐analysis to verify this association. Methods The publication studies on the IL‐10 (−1082G/A) polymorphism and CVDs risk were obtained by searching PubMed and Embase databases. We analyzed the genotype data for meta‐analysis. The results were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Meanwhile, our meta‐analysis was also performed sensitivity analyses, heterogeneity test, and identification of publication bias. Results The present meta‐analysis suggested that the risk with allele G is lower than with allele A for CVD. The G allele of IL‐10 (−1082) could increase the risk of CVDs in the 31 case–control studies for all genetic models. (OR = 1.10, 95% CI: 1.04–1.15 for the allele model A vs. G; OR = 0.87, 95% CI: 0.72–1.04 for the dominant model GG+AG vs. AA; OR = 1.03, 95% CI: 1.02–1.05 for the recessive model GG vs. AG + AA; OR = 1.06, 95% CI = 1.03–1.10 for the homozygote comparison model GG vs. AA; and OR = 0.88, 95% CI = 0.73–1.06 for the heterozygote comparison model AG vs. AA). Conclusions In genetic models, the association between the IL‐10 (−1082G/A) polymorphism and CVDs risk was significant. This meta‐analysis proposes that the IL‐10 (−1082G/A) polymorphism may serve as a risk factor for CVDs

Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD) prevalence in a large Japanese population.</p> <p>Methods</p> <p>A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs) in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m²) of the subjects were compared among the genotypes.</p> <p>Results</p> <p>A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of <it>IL4 </it>-33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and <it>IL6 </it>-572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with <it>IL4 </it>CC + <it>IL6 </it>GG showed the highest mean eGFR (79.1 ml/min/1.73 m²) and lowest CKD prevalence (0.0%), while subjects carrying <it>IL4 </it>TT + <it>IL6 </it>CC showed the lowest mean eGFR (73.4 ml/min/1.73 m²) and highest CKD prevalence (17.9%).</p> <p>Conclusions</p> <p>The functional promoter polymorphisms <it>IL4 </it>T-33C (rs2070874) and <it>IL6 </it>C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.</p