Differential expression and correlation of immunoregulation related piRNA in rheumatoid arthritis

BackgroundAlthough PIWI-interacting RNAs (piRNAs) have recently been associated with germline development and many human diseases, their expression pattern and relationship in autoimmune diseases remain indistinct. This study aimed to investigate the presence and correlation of piRNAs in rheumatoid arthritis (RA).MethodsWe first analyzed the expression profile of piRNAs using small RNA sequencing in peripheral leukocytes of three new-onset untreated RA patients and three healthy controls (HCs). We then selected piRNAs related to immunoregulation by bioinformatics analysis and verified them in 42 new-onset RA patients and 81 HCs by RT-qPCR. Furthermore, a receiver operating characteristic curve was generated to quantify the diagnostic performance of these piRNAs. A correlation analysis was conducted to observe the link between piRNA expression and RA clinical characteristics.ResultsA total of 15 upregulated and 9 downregulated piRNAs among 1,565 known piRNAs were identified in peripheral leukocytes of RA patients. Dysregulated piRNAs were enriched in numerous pathways related to immunity. After selection and validation, two immunoregulation piRNAs (piR-hsa-27620 and piR-hsa-27124) were significantly elevated in RA patients and have good abilities to distinguish patients from controls, which have the potential to serve as biomarkers. PIWI and other proteins implicated in the piRNA pathway were also associated with RA

OR-008 ERK-BAX signaling is involved in GLP-1-mediated antidepressant effects of metformin and exercise in CUMS mice

Objective Both depression itself and antidepressant medication have been reported to be significantly related to the risk of type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a treatment target for T2DM, has a neuroprotective effect. As an enhancer and sensitiser of GLP-1, metformin has been reported to be safe for the neurodevelopment. The present study aimed to determine whether and how GLP-1 mediates antidepressant effects of metformin and exercise in mice. Methods Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 8 weeks. From the 4th week, CUMS mice were subjected to oral metformin treatment and/or treadmill running. A videocomputerized tracking system was used to record behaviors of mice for a 5-min session. ELISA, western blotting and immunohistochemistry were used to examine gene expression in mouse serum or hippocampus. Results Our results supported the validity of metformin as a useful antidepressant; moreover, treadmill running favored metformin effects on exploratory behaviors and serum corticosterone levels. CUMS reduced GLP-1 protein levels and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), but increased protein levels of B-cell lymphoma 2-associated X-protein (BAX) in mice hippocampus. All these changes were restored by both single and combined treatment with metformin and exercise. Conclusions Our findings have demonstrated that ERK-BAX signaling is involved in GLP-1-mediated antidepressant effects of metformin and exercise, which may provide a novel topic for future clinical research

New Mothers' Survey in 2008 in rural China : A CHIMACA report

CHIMACA = Structural hinders to and promoters of good maternal care in rural ChinaLiitteenä kyselylomakkeet englannin ja kiinan kielell

Maternal care in rural China: a case study from Anhui province

<p>Abstract</p> <p>Background</p> <p>Studies on prenatal care in China have focused on the timing and frequency of prenatal care and relatively little information can be found on how maternal care has been organized and funded or on the actual content of the visits, especially in the less developed rural areas. This study explored maternal care in a rural county from Anhui province in terms of care organization, provision and utilization.</p> <p>Methods</p> <p>A total of 699 mothers of infants under one year of age were interviewed with structured questionnaires; the county health bureau officials and managers of township hospitals (n = 10) and county level hospitals (n = 2) were interviewed; the process of the maternal care services was observed by the researchers. In addition, statistics from the local government were used.</p> <p>Results</p> <p>The county level hospitals were well staffed and equipped and served as a referral centre for women with a high-risk pregnancy. Township hospitals had, on average, 1.7 midwives serving an average population of 15,000 people. Only 10–20% of the current costs in county level hospitals and township hospitals were funded by the local government, and women paid for delivery care. There was no systematic organized prenatal care and referrals were not mandatory. About half of the women had their first prenatal visit before the 13th gestational week, 36% had fewer than 5 prenatal visits, and about 9% had no prenatal visits. A major reason for not having prenatal care visits was that women considered it unnecessary. Most women (87%) gave birth in public health facilities, and the rest in a private clinic or at home. A total of 8% of births were delivered by caesarean section. Very few women had any postnatal visits. About half of the women received the recommended number of prenatal blood pressure and haemoglobin measurements.</p> <p>Conclusion</p> <p>Delivery care was better provided than both prenatal and postnatal care in the study area. Reliance on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care.</p

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis

Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57–0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45–2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15–1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32–3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56–2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32–0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles

Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus

Background & objectives: The presence of CD4+CD8+ (double positive) T cells (DPT) in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE). Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA), anti-double strain deoxyribonucleic acid (anti-dsDNA), anti-U1 ribonucleoprotein (anti-U1 RNP), anti-sjogren syndrome A (anti-SSA), anti-ribosomal P protein (anti-rib-P), anti-Smith (anti-Sm), anti-Sjogren syndrome B (anti-SSB), complement 3 (C3) and complement 4 (C4). Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001). SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032). The DPT medians of positive subgroups with anti-dsDNA (P<0.001), anti-U1RNP (P=0.018), anti-SSA (P=0.021) or anti-rib-P (P=0.039) were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006). Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work

IL-1 β and IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype

textabstractBackground. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1β, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1β) were measured in sera of familial SLE patients (n=3), noninherited SLE patients (n=108), and healthy controls (n=80). Results. Three familial SLE patients and 5 noninherited SLE cases are with features of RF+IgE+. These RF+IgE+ SLE patients expressed significantly higher levels of IL-1β and IL-6 than the other SLE patients (P<0.05). IL-6 correlated with both IgE and IL-1β levels in RF+IgE+ SLE patients (r2=0.583, P=0.027; r2=0.847, P=0.001), and IgE also correlated with IL-1β (r2=0.567, P=0.031). Conclusion. Both IL-1β and IL-6 are highly expressed cytokines in RF+IgE+ SLE subtype which may be related to the pathogenesis of this special SLE subtype and provide accurate treatment strategy by neutralizing IL-1β and IL-6

Association of E26 Transformation Specific Sequence 1 Variants with Rheumatoid Arthritis in Chinese Han Population

<div><p>Objective</p><p>E26 transformation specific sequence 1 (ETS-1) belongs to the ETS family of transcription factors that regulate the expression of various immune-related genes. Increasing evidence indicates that ETS-1 could contribute to the pathogenesis of autoimmune disease. Recent research has provided evidence that ETS-1 might correlate with rheumatoid arthritis (RA), but it's not clearly defined. In this study, we aimed to identify whether polymorphisms of ETS-1 play a role in Rheumatoid arthritis (RA) susceptibility and development in Chinese Han population.</p><p>Methods</p><p>Four single nucleotide polymorphisms (SNPs) within ETS-1 were selected based on HapMap data and previous associated studies. Whole blood and serum samples were obtained from 158 patients with RA and 192 healthy subjects. Genotyping was performed with polymerase chain reaction-high resolution melting (PCR-HRM) assay and the data was analyzed using SPSS17.0.</p><p>Results</p><p>A significantly positive correlation was observed between the SNP rs73013527 of ETS-1 and RA susceptibility, DAS28 and CRP (P<0.001, P = 0.001, and P = 0.028, respectively). Carriers of the haplotype CCT or TCT for rs4937333, rs11221332 and rs73013527 were associated with decreased risk of RA as compared to controls. No statistical significant difference was observed in the distribution of rs10893872, rs4937333 and rs11221332 genotypes between RA patients and controls.</p><p>Conclusions</p><p>Our data further supports that ETS-1 has a relevant role in the pathogenesis and development of RA. Allele T of rs73013527 plays a protective role in occurrence of RA but a risk factor in the high disease activity. Rs10893872, rs11221332 and rs4937333 are not associated with RA susceptibility and clinical features.</p></div

Linkage disequilibrium for four SNPs in 350 individuals.

<p>The linkage disequilibrium plot shows r² values between each pair of SNPs. rs10893872 and rs4937333 were in strong LD (black squares). D’ = 1.000, r2 = 0.980.</p

Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA Nephropathy in Adults from a Chinese Han Population.

MicroRNA 146a (miR-146a) is a 19 to 23 nucleotide long, small non-coding RNA with gene regulatory functions that has influence on the pathogenesis of many diseases. A single nucleotide polymorphism (rs2910164 C>G) in pre-miR-146a is correlated with the expression of miR-146a. The aim of this study was to perform an association analysis of rs2910164 with IgA nephropathy in adult patients from a Chinese Han population.A total of 145 patients with renal biopsy-proved IgA nephropathy (IgAN) and 179 healthy controls were recruited to the current study. rs2910164 was genotyped by the polymerase chain reaction (PCR) and high-resolution melting methods (HRM). Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of kidney biopsy.There were significant differences among the population of patients grouped by different age of onset in a co-dominant model (CG vs. CC vs. GG) (p = 0.033) and a recessive model (CG+CC vs. GG) (p = 0.001). However, no significant difference was observed in the distribution of genotypes between cases and controls (p = 0.144). There was also no significant difference between rs2910164 and patient quantitative traits (all p > 0.003) or different pathology grading (Lee's grading system and tubular atrophy/interstitial fibrosis in the Oxford classification) (all p > 0.05).There was no association of rs2910164 with susceptibility to IgAN in adults from a Chinese Han population. However, rs2910164 was correlated with the age of onset of IgAN in adult patients