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: Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise.', "Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient.", 'Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α).
Answer: Our results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network.
Does physical exercise alleviate ER stress in obese humans through reduction in the expression and release of GRP78 chaperone?

Context: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC).', 'Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo.', 'miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice.
Answer: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.
Does microRNA-361-5p inhibit Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma?

Context: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis.', 'To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis).', 'The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05).
Answer: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies.

Does angiogenesis and proliferation of bile duct enhance ischemic tolerance in rats with cirrhosis?