Association between genetic variants and development of antibodies to infliximab: A cross-sectional study in Chinese patients with Crohn’s disease

Aims: Genetic variants increase the susceptibility to anti-drug antibodies (ADA) in response to anti-TNF therapy in chronic inflammatory diseases. However, little is known about genetic variants in Chinese populations. This study aimed to identify genetic variants contributing to the risk of the development of antibodies to infliximab (ATI) in Chinese patients with Crohn’s disease (CD).Methods: CD patients (n = 104) treated with infliximab (IFX) during the maintenance therapy were enrolled in this cross-sectional study. ATI was assessed by an in-house developed drug-tolerant ELISA method. ATI titers of 1:20 and ≥1:60 were considered a low titer and a high titer, respectively. Thirteen types of single nucleotide polymorphisms (SNPs) within 13 genes involved in the immune process, the susceptibility to chronic inflammatory diseases, cytokines and apoptosis pathways were investigated.Results: The median trough levels of infliximab (TLI) in patients with clinical remission (CR) were higher than those in patients without CR (3.80 vs. 1.50 μg/mL, p < .001). The median TLI in patients with high-titer ATI was significantly lower than that in ATI-negative patients (1.15 vs. 4.48 μg/mL, p < .001) or those with low-titer ATI (1.15 vs. 2.95 μg/mL, p = .03). The HLA-DQA1*05 rs2097432 GG and GA genotypes were more frequent in patients with ATI (GG and AG vs. AA, 27/38 = 71.05% vs. 29/66 = 43.94%, OR 2.94, 95% CI 1.19–7.30, p = .02). Patients carrying the CC and AC genotypes of rs396991 in FCGR3A were associated with a higher frequency of ATI formation (CC and AC vs. AA, 37/57 = 64.91% vs. 19/47 = 40.43%, OR 2.94, 95% CI 1.24–6.96, p = .01). According to the number of variants in rs2097432 and rs393991, patients with two variants had a higher proportion of producing ATI (two variants vs. no variant, 17/21 = 80.95% vs. 9/30 = 30.00%, OR 9.92, 95% CI 2.59–37.87, p = .001; single variant vs. no variant, 30/53 = 56.60% vs. 9/30 = 30.00%, OR 3.04, 95% CI 1.18–7.88, p = .02). No association was found between other SNPs and ATI production.Conclusion: Rs2097432 in HLA-DQA1*05 and rs396991 in FCGR3A are associated with ATI production in Chinese patients with CD. A pharmacogenomic strategy could help with the clinical management of CD

Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naive, First-Episode Drug-Free Schizophrenia

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients. Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied. Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P \u3c 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P \u3c 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = -0.345,-0.369,-0.444, respectively, P \u3c 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = -0.316 to -0.553, P \u3c 0.05). Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naive, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients

Social capital influences farmer participation in collective irrigation management in Shaanxi Provence, China

Purpose – The purpose of this paper is to investigate the influence of four components of social capital on farmers’ participative behaviour in collective actions for constructing and operating small-scale groundwater irrigation systems on the Guanzhong Plain, Shaanxi Province, China. Design/methodology/approach – The four components (social networks, social trust, social reciprocity and social participation) were derived by employing exploratory factor analysis. Logistic model was used to estimate the influence of these components on farmers’ participative behaviour. Information was obtained from a field survey covering six counties in 2011 of Shaanxi Province, China. Findings – The findings indicate that considering different components of social capital allows for a better understanding of farmers’ participative behaviour. The authors find that higher levels of social trust and social participation lead to a higher propensity for collective action, while social reciprocity reduces the probability of participation. Other socio-economic factors and farming characteristics such as education levels, cultivated area, cropping patterns and grain subsidies also have a significant impact. Practical implications – The findings suggest creating favourable conditions for communication and information exchanges between households, which enhance their trust of each other, and encourage farmers to participate in collective affairs. Moreover, supportive rules are necessary for the future development of collective action. The results of this study also have implications for national irrigation plans for small-scale irrigation facilities in other developing countries. Originality/value – A consideration of the different components of social capital allows for a more precise understanding of farmers’ participative behaviour

Expression and clinical significance of LXRα and SREBP-1c in placentas of preeclampsia

To evaluate the expression and correlations of liver X receptor alpha (LXRa) and its target gene sterol regulatory element-binding protein-1c (SREBP-1c) in placentas of preeclampsia (PE) and their significance in PE

Income Groups, Social Capital, and Collective Action on Small-Scale Irrigation Facilities : A Multigroup Analysis Based on a Structural Equation Model

This article examines whether relationships between social capital characteristics and the willingness of farmers to cooperate in collective action is moderated by the farmers' income level. We employed a structural equation model to analyze the influence of social capital components (social networks, interpersonal trust, social reciprocity, and social participation) on the willingness of farmers to cooperate in collective small-scale irrigation in Guangling County, Shanxi Province of China. This analysis was complemented by a multigroup analysis to measure the potential variance effects across income groups. Our results show that low- and middle-income farmers give more importance to the aspects of social networks, social reciprocity, and social participation, while high-income farmers place emphasis on interpersonal trust and social participation. Accordingly, the willingness of farmers to cooperate for the different income groups was influenced in different ways in relation to the various social capital components. Therefore, social capital and income differences have complex effects on the willingness of farmers to cooperate. In this regard, our research provides an alternative way to understand the complex process involved in the formation of collective action under the presence of increasing economic heterogeneity in local communities

Integrating genomic sequencing resources: an innovative perspective on recycling with universal Angiosperms353 probe sets

Abstract Sequencing strategies have continually advanced, with high-throughput sequencing (HTS) technologies emerging as pivotal tools in plant phylogenomics. As a standard form of target capture sequencing, hybridization target enrichment sequencing (Hyb-seq) is innovative and flexible, and then HTS strategy is widely adopted in phylogenomics. The universal Angiosperms353 probe sets (Angiosperms353) are instrumental in Hyb-seq and have been witnessed increased application in recent years. This review integrates numerous publications and empirical datasets to comprehensively assess the potential applications of Angiosperms353. Through evaluations using 18-taxa and 343-taxa genomic datasets, this review explores potential factors influencing Angiosperms353 gene capture. The RNA-seq strategy yielded the highest number of Angiosperms353 genes, followed by whole-genome sequencing and genome skimming. Increased sequencing depth enhanced gene capture yields, and no evident bias was observed across all tested angiosperm groups. In the genomics era with extensive HTS data, this review provides comprehensive guidelines for the practical application of Angiosperms353, promoting resource recycling and maximizing genomic data sharing and utilization

MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells

Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed in many types of cancers including prostate carcinoma, but the mechanisms underlying this event remain largely unknown. Here we investigated the expression of miR199b and HIF-1α in normal prostate tissue, prostate cancer tissues and prostate carcinoma (PCa) cell lines LNCaP, PC-3 and DU145.We found that miR-199b expression level was decreased in prostate cancer while HIF-1α was significantly over-expressed. Furthermore, we postulated the posttranscriptional regulation of HIF-1α by miR199b through bioinformatics analysis, and herein we experimentally demonstrated that miR199b negatively regulated HIF-1α by targeting its 3'-untranslated region. Artificial over-expression of miR199b by using adenoviral vectors in prostate cancer PC-3 and DU145 cells significantly down-regulated HIF-1α, together with reduced cell growth and increased cell death