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.
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Question: 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 µmol/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-κB) 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-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB 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.

Answer: Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?


Question: Context: To evaluate whether P2X3 receptors (P2X3R) are expressed in the bladder urothelium and to determine their possible function in modulating purinergic detrusor contractions in the rat urinary bladder.', 'The expression of urothelial receptors was determined using conventional immunohistochemistry in bladders from normal Sprague-Dawley rats. The urothelial layer was removed by incubation with protamine, and disruption of the urothelium was confirmed using haematoxylin and eosin staining on bladder sections. Open cystometry was used to determine the effects of both urothelial removal as well as intravesical application of a specific P2X3R antagonist on bladder properties from intact and protamine-treated rats. Isometric contractile responses to potassium chloride (KCl) depolarization, electrical field stimulation (EFS) or chemical P2X activation were determined in normal and urothelium-denuded bladder strips, with and without application of the P2X3R antagonist.', 'Immunohistochemical staining showed high expression of P2X3R in the medial and basal layers of the urothelium. Removal of the urothelial layer disturbed normal bladder performance in vivo and eliminated the effects of the P2X3R antagonist on increasing the contractile interval and reducing the amplitude of voiding contractions. Removal of the urothelium did not affect bladder strip contractile responses to KCl depolarization or EFS. Pharmacological inhibition of P2X3R prevented desensitization to P2X-mediated detrusor muscle contractions during EFS only in the strips with an intact urothelium. A concentration-dependent, specific inhibition of P2X3R also prevented desensitization of purinergic contractile responses in intact bladder strips.
Answer: In the rat bladder, medial and basal urothelial cells express P2X3R, and specific inhibition of the receptor leads to a more hyporeflexive bladder condition. This pathway may involve P2X3R driving a paracrine amplification of ATP released from umbrella cells to increase afferent transmission in the sub-urothelial sensory plexus and desensitization of P2X1-mediated purinergic detrusor contractions.

Answer: Does inhibition of urothelial P2X3 receptors prevent desensitization of purinergic detrusor contractions in the rat bladder?


Question: Context: Several factors influence the outcome after acute ischemic stroke secondary to proximal occlusions of cerebral vessels. Among others, noneligibility for intravenous thrombolysis (IVT) and incomplete revascularization have been identified as predictors of unfavorable outcome. The aim of this study was to investigate whether concomitant IVT influences the revascularization efficacy in mechanical thrombectomy (MT).', 'This study conducted a retrospective analysis of all consecutive patients presenting with an anterior circulation stroke due to large-artery occlusion with imaging evidence who were treated with MT between July 2012 and December 2013 at 2 high-volume stroke centers. Imaging data were regraded and re-evaluated according to the modified Treatment in Cerebral Ischemia scale and its respective vessel occlusion site definitions. Clinical end points included National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale; imaging and procedural measures were technical end points.', 'We identified 93 patients who presented with an occlusion of the middle cerebral artery (MCA): of these patients, 66 (71%) received IVT. We did not find statistically significant differences in the baseline NIHSS score, time from symptom onset to groin puncture, and age when comparing the IVT group with the non-IVT group. The rate of successful recanalizations (modified Treatment in Cerebral Ischemia score\u2009≥\u20092b) was significantly higher in patients with MCA occlusion and concomitant IVT (P\u2009=\u2009.01). Stepwise logistic regression identified IVT and thrombus length as predictive factors for successful mechanical recanalization (P\u2009=\u2009.004, P\u2009=\u2009.002).
Answer: IVT and thrombus length are predictive factors for a successful recanalization in MT for acute ischemic stroke with underlying MCA occlusion.

Answer:
Does intravenous Thrombolysis facilitate Successful Recanalization with Stent-Retriever Mechanical Thrombectomy in Middle Cerebral Artery Occlusions?