The current study was to determine the predictors of survival in 491 Chinese patients with lupus nephritis (LN). All patients were evaluated and consecutively followed up from 2003 to 2010. The female: male ratio was 9.5:1, with a median age of 31.1 ± 12 years. Forty-nine (10.0%) patients were lost to follow-up and 47 (10.3%) patients died. The overall cumulative probability of survival at 5, 10, 15 and 20 years by Kaplan-Meier analysis was 88%, 77%, 53% and 45%, respectively. The log-rank test showed that the probability of survival was significantly decreased in the late-onset patients (≥50 years) (P = 0.036), patients with hypoproteinaemia (≤35 g/l) (P = 0.014), patients with increased creatinine (≥1.5 mg/dl) (P = 0.002) and patients with massive proteinuria (≥3.5 g/24 h) (P = 0.009). However, the probability of survival was significantly higher in patients treated with hydroxychloroquine (HCQ) (P = 0.003) than those not treated with it. Based on a multivariate model, increased creatinine (hazard ratio (HR) = 2.041; P = 0.017) and proteinuria ≥3.5 g/24hours (HR=1.716; P = 0.016) were independent risk factors. Glucocorticoid (HR = 0.457; P = 0.01) and HCQ (HR=0.197; P = 0.026) were independent protective factors. Our findings suggest that renal dysfunction and massive proteinuria are independent risk factors for mortality. HCQ could improve the survival of patients with LN.
Interferon-γ (IFN-γ), a pleiotropic lymphokine, has important regulatory effects on many cell types. Although IFN-γ is essential for the initiation of uterine vascular modifications and maintenance of decidual integrity, IFN-γ administration can also cause pregnancy failure in many species. However, little is known about the effector mechanisms involved. In this study, using an IFN-γ-induced abortion mouse model, we reported that no Dolichos biflorus agglutinin lectin-positive uterine natural killer (uNK) cells were observed in the uteri from IFN-γ-induced abortion mice. By contrast, the percentage of CD3−CD49b+ NK cells in the uterus and blood from a foetal resorption group was significantly higher than that of the control group. Similarly, significantly upregulated expression of CD49b (a pan-NK cell marker), CX3CL1 and CX3CR1 (CX3CL1 receptor) was detected in the uteri of IFN-γ-induced abortion mice. Using isolated uterine stromal cells, we showed that upregulated expression of CX3CL1 by IFN-γ was dependent on a Janus family kinase 2-signal transducers and activators of transcription 1 (JAK2-STAT1) pathway. We further demonstrated the chemotactic activity of CX3CL1 in uterine stromal cell conditioned medium on primary splenic NK cells. Finally, we observed increased recruitment of CD49b+ NK cells into the endometrium after exogenous CX3CL1 administration. Collectively, our findings indicate that IFN-γ can significantly increase uterine CX3CL1 expression via activation of the JAK2-STAT1 pathway, thus inducing CD49b+ NK cell uterine homing, and eventually provoke foetal loss. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ on pregnancy with the aberrant regulation of CX3CL1 and CD49b+ NK cells.
ABSTRACT. In lily flowers, the volatile ester methyl benzoate is one of the major and abundant floral scent compounds; however, knowledge regarding the biosynthesis of methyl benzoate remains unknown for Lilium. In this study, we isolated a benzoic acid/salicylic acid carboxyl methyltransferase (BSMT) gene, LiBSMT, from petals of Lilium 'Yelloween'. The gene has an open reading frame of 1083 base pairs (bp) and encodes a protein of 41.05 kDa. Sequence alignment and phylogenetic analyses of LiBSMT revealed 40-50% similarity with other known benzenoid carboxyl methyltransferases in other plant species, and revealed homology to BSMT of Oryza sativa.
Parthenogenetic cells are lost from fetal chimeras. This may be due to decreased proliferative potential. To address this question, we have made use of combined cell lineage and cell proliferation analysis. Thus, the incorporation of bromodeoxyuridine in S-phase was determined for both parthenogenetic and normal cells in several tissues of fetal day 13 and 17 chimeras. A pronounced reduction of bromodesoxyuridine incorporation by parthenogenetic cells at both developmental stages was only observed in cartilage. In brain, skeletal muscle, heart and intestinal epithelium, this reduction was either less pronounced or observed only at one of the developmental stages analysed. No difference between parthenogenetic and normal cells was observed in epidermis and ganglia. Our results show that a loss of proliferative potential of parthenogenetic cells during fetal development contributes to their rapid elimination in some tissues. The analysis of the fate of parthenogenetic cells in skeletal muscle and cartilage development demonstrated different selection mechanisms in these tissues. In skeletal muscle, parthenogenetic cells were largely excluded from the myogenic lineage proper by early post-midgestation. In primary hyaline cartilage, parthenogenetic cells persisted into adulthood but were lost from cartilages that undergo ossification during late fetal development.
Colorectal cancer (CRC) is the third common cancer and most of the chemotherapies of CRC currently used often suffer limited efficacy and large side effects. Targeted small-molecule by anti-tumor drugs are thought a promising strategy for improving the efficacy and reducing the side effects. In this investigation, we report a novel multikinase inhibitor, termed SKLB-287, which was discovered by us recently. SKLB-287 could efficiently inhibit the activation of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2). It displayed very good anti-proliferative activity against LoVo CRC cells and considerable antiangiogenic potency in transgenic zebrafish embryos. Oral administration of SKLB-287 resulted in dose-dependent suppression of tumor growth in LoVo xenograft mouse model. Immunohistochemistry was adopted to examine the in vivo anti-tumor mechanism of action of SKLB-287.
Objective To estimate concurrent co-morbidity of body mass index (BMI) (underweight/overweight/obesity vs 'normal') groups with psychological distress and assess the direction of association at different life-stages. Design and Setting Prospective birth cohort born in 1958 in England, Scotland, and Wales (≈17,000) with eight data collections. Participants 12,918 participants at age 7 years followed-up to 50 years. Main Outcomes Psychological distress was assessed with ageappropriate instruments: Teacher-Rated Bristol Adjustment (7-11 years) and Rutter Scale (16 years) (scores in the top 13%), and Psychological Malaise Inventory at 23-50 years (scores >5). Depression and anxiety symptoms were obtained at 45 years. BMI groups were calculated from measured (7, 11, 16, 33, copyright.
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