Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.", 'Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.
Answer: These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.
Are plasma PCSK9 levels significantly modified by statins and fibrates in humans?

Context: Current knowledge of the potential effects that several dietary lipids exert on immune functions indicates that these substances participate actively in the modulation of immune system by which they contribute to the improvement of the conditions of patients suffering from inflammatory disorders. However, long-chain n-3 polyunsaturated fatty acids induce an immunosuppressive status that leads to a reduction of the host natural resistance to infectious agents as well as to an enhancement of oxidative damage. Hence, the present study has been designed to evaluate the effects on the immune system of the antioxidant N-acetyl-L-cysteine (NAC) in mice fed dietary lipids and infected with Listeria monocytogenes.', 'Balb/c mice were fed for 4 weeks with diets containing either olive oil (OO, 20% by weight), fish oil (FO, 20% by weight) or hydrogenated coconut oil (HCO, 20% by weight). After dietary lipid administration mice were experimentally infected with L. monocytogenes or treated with NAC (25mg/ml intraperitoneally).', 'NAC at a concentration of 1mM promoted a loss of cell viability, although no differences were observed among the four groups. After injection of NAC in combination with L. monocytogenes, 25% of mice fed a low-fat (LF) diet survived. However, in the groups fed dietary lipids no effect on survival of mice was found. NAC participated in the reduction of superoxide anion generation measured with nitroblue tetrazolium (NBT) in the group fed a FO diet. Finally, NAC reduced the recovery of L. monocytogenes from spleen of mice fed diets containing LF or HCO.
Answer: On the basis of these results, we can confirm that the administration of NAC improves survival in mice fed LF diet, whereas a reduction in the generation of superoxide radicals was measured in mice fed a FO diet and infected with L. monocytogenes. Similarly, bacterial recovery was diminished in mice fed diets containing LF or HCO. Hence, these data reveal a beneficial effect of NAC in mice fed LF or HCO and a detrimental action of this antioxidant in mice fed diets containing FO or OO.
Do anti-oxidant properties of N-acetyl-L-cysteine improve the immune resistance of mice fed dietary lipids to Listeria monocytogenes infection?

Context: Baseline carbohydrate antigen 19-9 (CA 19-9) is a useful prognostic marker in pancreatic ductal adenocarcinoma (PDA); however, data on the significance of a change in CA 19-9 following neoadjuvant therapy are lacking.', "All patients receiving neoadjuvant therapy for PDA from July 2010 to February 2013 were retrospectively reviewed. Resection rate, R0 resection rate, need for venous resection, and overall survival were correlated to CA 19-9 response. Fisher's exact test, Kaplan-Meier survival analysis, and multivariate analysis using Cox regression were used.", 'A total of 78 patients were studied (21 patients with resectable disease, 40 borderline resectable, and 17 with locally advanced disease). A variety of chemotherapies ± radiation were utilized during the study period. Overall, 56 patients (72 %) had a decrease in CA 19-9 of >50 % with neoadjuvant treatment. In borderline resectable patients, CA 19-9 response of >50 % predicted R0 resection (odds ratio 4.2; p = 0.05). In borderline resectable patients who had an increase in CA 19-9, none of five (0 %) underwent R0 resection compared with 80 % of the remaining cohort (p = 0.001). The complete pathologic response rate was 29 % in patients who had a CA 19-9 response of >90 % versus 0 % in the remaining patients (p < 0.001). A CA 19-9 response of >50 % resulted in improved overall survival (28.0 vs. 11.1 months; p < 0.0001) and was an independent predictor of survival (hazard ratio 0.26; 95 % CI 0.13-0.55; p < 0.0001).
Answer: CA 19-9 response to neoadjuvant therapy is associated with R0 resection rate, histopathologic response, and survival. Incorporation of this easily obtainable biomarker into future clinical trials may facilitate more rapid evaluation of novel regimens.

Is serum CA 19-9 response to neoadjuvant therapy associated with outcome in pancreatic adenocarcinoma?