Given a passage, 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.

[Q]: The proteasome is a major cellular proteinase. Its activity is modulated by cellular oxidants. Hepatitis C core protein and ethanol exposure both cause enhanced oxidant generation. The aim was to investigate whether core protein, by its ability to generate oxidants, alters proteasome activity and whether these alterations are further affected by ethanol exposure.', 'These interactions were examined in Huh-7 cell lines that expressed inducible HCV core protein and/or constitutive cytochrome P450 2E1 (CYP2E1) and as purified components in a cell-free system. Chymotrypsin-like proteasome activity was measured fluorometrically.', 'Proteasome activity in core-positive 191-20 cells was 20% higher than that in core-negative cells and was enhanced 3-fold in CYP2E1-expressing L14 cells. Exposure of core-positive cells to glutathione ethyl ester, catalase, or the CYP2E1 inhibitor diallyl sulfide partially reversed the elevation of proteasome activity in core-positive cells, whereas ethanol exposure suppressed proteasome activity. The results indicate that proteasome activity was up-regulated by low levels of core-induced oxidative stress but down-regulated by high levels of ethanol-elicited stress. These findings were partially mimicked in a cell-free system. Addition of core protein enhanced the peptidase activity of purified 20S proteasome containing the proteasome activator PA28 and was further potentiated by addition of liver mitochondrial and/or microsome fractions. However, proteasome activation was significantly attenuated when fractions were obtained from ethanol-fed animals.
[A]: Is proteasome activation by hepatitis C core protein reversed by ethanol-induced oxidative stress?


[Q]: To investigate the role of nitric oxide (NO)-induced autophagy in human dental pulp cells (HDPCs) and the involvement of AMP-activated protein kinase (AMPK) pathway.', "The MTT assay was used to determine the cytotoxic effect of the NO donor sodium nitroprusside (SNP) in HDPCs. Apoptosis was detected by means of the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and apoptosis- or autophagy-related signal molecules were observed by Western blot analysis. Acidic autophagolysosomal vacuoles were stained with acridine orange to detect autophagy in the presence of 3-methyladenine (3MA) used to inhibit autophagy. To explore the mechanism underlying autophagy and its protective role against apoptosis, compound C, the chemical AMPK inhibitor, was used. Statistical analysis was performed using Student's t-test or analysis of variance (ANOVA) followed by the Student-Newman-Keuls test (p<0.05).", 'SNP decreased viability of the HDPCs in a dose- and time-dependent manner. Exposing the HDPCs to SNP increased the levels of p62 and LC3-II, the typical markers of autophagy, and increased the number of acidic autophagolysosomal vacuoles, indicating the appearance of autophagy as detected by acridine orange staining (p<0.05). Pretreatment with 3MA decreased cell viability but increased cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, apoptosis indicators, in the SNP-treated HDPCs (p<0.05). SNP activated AMPK/ULK signaling, while the inhibition of AMPK by compound C enhanced apoptotic cell death induced by SNP in the HDPCs (p<0.05).
[A]: Do nitric oxide-induced autophagy and the activation of AMPK pathway protect against apoptosis in human dental pulp cells?


[Q]: Aberrant expression of the cell cycle kinase inhibitors p16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome.', 'A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p16, p21, and p27 using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system.', 'High p16 (> or =5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (< or =50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p16 was related to lower patient age and low expression of p53. High expression of p16 indicated a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2-1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2-0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3-9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables.
[A]:
Does p16INK4a and p21Waf1/Cip1 expression correlate with clinical outcome in vulvar carcinomas?