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: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.', 'The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 mol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.', 'Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-B p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-B p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).
Answer: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.
Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?

Context: Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2(loxP/loxP) Villin-Cre mouse model for Lynch syndrome.', 'Flow cytometry was used for quantitation of mutation rates at a CA13 microsatellite in human colon cancer (HCT116) cells that had been stably transfected with pIREShyg2-enhanced green fluorescent protein/CA13, a reporter for frameshift mutations. Mice were treated for 43weeks with mesalazine, thymoquinone or control chow. Intestines were analysed for tumour incidence, tumour multiplicity and size. MSI testing was performed from microdissected normal intestinal or tumour tissue, compared with mouse tails and quantified by the number of mutations per marker (NMPM).', 'Besides mesalazine, thymoquinone significantly improved replication fidelity at 1.25 and 2.5M in HCT116 cells. In Msh2(loxP/loxP) Villin-Cre mice, tumour incidence was reduced by mesalazine from 94% to 69% (p=0.04) and to 56% (p=0.003) by thymoquinone. The mean number of tumours was reduced from 3.1 to 1.4 by mesalazine (p=0.004) and to 1.1 by thymoquinone (p<0.001). Interestingly, MSI was reduced in normal intestinal tissue from 1.5 to 1.2 NMPM (p=0.006) and to 1.1 NMPM (p=0.01) by mesalazine and thymoquinone, respectively. Thymoquinone, but not mesalazine, reduced MSI in tumours.
Answer: Mesalazine and thymoquinone reduce tumour incidence and multiplicity in Msh2(loxP/loxP) Villin-Cre mice by reduction of MSI independent of a functional mismatch repair system. Both substances are candidate compounds for chemoprevention in Lynch syndrome mutation carriers.
Do mesalazine and thymoquinone attenuate intestinal tumour development in Msh2 ( loxP/loxP ) Villin-Cre mice?

Context: The aim of this study was the measurement of maternal serum levels of M-CSF throughout pregnancy, in a low risk obstetrical population, to examine the relationship of M-CSF and pregnancy outcome.', 'Maternal serum was obtained at various stages of pregnancy and post partum, M-CSF levels were measured by ELISA, pertinent clinical data tabulated, and pregnancy outcome was determined.', 'In 564 pregnancies studied, 22% of 260 nulliparous pregnancies and 10% of 304 multiparous pregnancies were hypertensive. Preeclampsia occurred in 1.5% of nulliparous and in 1% of the multiparous women. In apparently normal pregnancies with good outcome, M-CSF levels rose throughout pregnancy. No cases of preeclampsia occurred if maternal serum M-CSF levels increased more than 100% throughout pregnancy.
Answer: This study suggests that absolute levels and relative changes in maternal serum M-CSF levels during pregnancy are associated with adverse pregnancy outcomes.
Are maternal serum levels of macrophage colony-stimulating factor associated with adverse pregnancy outcome?