instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\u2009<\u20090.05 and FC\u2009≥\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\u2009=\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.\Question: Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?
answer:
For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.


question:
Context: Stem cell factor (SCF) has well-known proliferative effects on hematopoietic cells. SCF also has effects on differentiation and proliferation in other cell types. Interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha have proliferative effects in the liver. Recent studies in our laboratory have linked SCF's hepatoproliferative actions to those of IL-6, demonstrating that IL-6-induced hepatocyte proliferation depends, at least in part, on SCF. We now hypothesize that TNF-alpha's hepatoproliferative effects are also dependent on SCF.", 'In vitro studies using primary mouse hepatocytes show that SCF is induced by TNF-alpha; anti-SCF antibody treatment in this system inhibits TNF-alpha-induced hepatocyte proliferation, suggesting that TNF-alpha-induced hepatocyte proliferation is also SCF dependent. Additional in vivo experiments were performed in which wild type and/or TNF-alpha receptor-1 knockout mice (TNFR1(-/-)) were subjected to 70% hepatectomy or sham laparotomy. TNFR1(-/-) mice are known to have delayed hepatic regeneration after partial hepatectomy. Initial experiments demonstrated that the SCF receptor, c-kit, is upregulated after partial hepatectomy in wild-type mice, further emphasizing the importance of this system in the restoration of hepatic mass. SCF administration to TNFR1(-/-) mice in the context of partial hepatectomy restores hepatocyte proliferation to normal. Further, SCF administration to TNFR1(-/-) mice before hepatectomy increases phosphotyrosine signal transducer and activator (p-stat-3) levels, suggesting that SCF-induced increases in hepatocyte proliferation may also be stat-3 mediated.\Question: Are stem cell factor and its receptor , c-kit , important for hepatocyte proliferation in wild-type and tumor necrosis factor receptor-1 knockout mice after 70 % hepatectomy?
answer:
These data suggest that TNF-alpha-induced hepatocyte proliferation depends, at least in part, on SCF and that SCF and its receptor, c-kit, are important for the liver's regenerative processes.


question:
Context: Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes.', 'Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real-time PCR and protein by Western blotting.', 'In human subjects, ZAG mRNA level was negatively correlated with BMI (r = -0.61, P < 0.001, n = 23, visceral; r = -0.6, P < 0.05, n = 14, subcutaneous) and fat mass (r = -0.62, P < 0.01, visceral; r = -0.6, P < 0.05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = -0.65, P < 0.001, visceral; r = -0.55, P < 0.05, subcutaneous) and homeostasis model of insulin resistance (HOMA-IR) (r = -0.65, P < 0.001, visceral; r = -0.52, P = 0.055, subcutaneous), and C reactive protein (CRP) (r = -0.46, P < 0.05, visceral; r = -0.53, P < 0.05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0.5, P < 0.05, visceral; r = 0.82, P < 0.001, subcutaneous) but negatively associated with leptin mRNA (r = -0.42, P < 0.05, visceral; r = -0.54, P < 0.05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes.\Question: Is the adipokine zinc-alpha2-glycoprotein ( ZAG ) downregulated with fat mass expansion in obesity?
answer:

ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity-related insulin resistance.