instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: The proteasome is the proteolytically active core of the ubiquitin-proteasome system, which regulates vital processes and which can cause various diseases when it malfunctions. Therefore, the proteasome has become an attractive target for pharmaceutical interventions. Inhibition of the cardiac proteasome by specific proteasome inhibitors has been shown to attenuate cardiac hypertrophy and ischaemia reperfusion injury of the heart. We have resolved the cardiac proteasome into its subtypes and have addressed the key question of how proteasome inhibitors affect single cardiac proteasomal subtypes.', 'The 20S proteasome from rat heart was dissected into three different subpopulations (groups I-III), each comprising 4-7 different subtypes. The major group (group II) comprises standard proteasome subtypes; the two minor subpopulations (groups I and III) contain intermediate proteasome subtypes. All subtypes exhibit chymotrypsin-, trypsin-, and caspase-like activity but to different degrees. We have tested the effect of two common proteasome inhibitors on the chymotrypsin-like activity of all subtypes: 20-30 nmol/L MG132 caused 50% inhibition of all subtypes from groups I and II, whereas 100 nmol/L was necessary to affect group III subtypes to the same extent. However, another inhibitor, bortezomib (VELCADE), already used clinically, inhibited 50% of the activity of group III proteasome subtypes even below 20 nmol/L, a concentration showing almost no effect on group I and II proteasome subtypes. The caspase-like activity of group II proteasome subtypes was not affected by MG132 and was inhibited by bortezomib only at concentrations above 100 nmol/L.\Question: Do multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors?
answer:
These data show that different inhibitors have differential inhibitory effects on the various cardiac proteasome subtypes. Different cardiac subtypes are inhibited by the same dose of proteasome inhibitor to a different extent.


question:
Context: To examine whether trichostatin A (TSA), a histone deacetylase inhibitor (HDACI), can induce up-regulation of peroxisome proliferator-activating receptor gamma (PPAR gamma) and to see whether LG100268, a retinoid X receptor (RXR) ligand, can inhibit proliferation of endometriotic cells alone or in synergy with ciglitazone, a PPAR gamma agonist.', 'One endometrial stromal cell line and two endometriotic cell lines used as a model system: Western blot analysis to determine whether TSA can up-regulate PPAR gamma expression, and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) proliferation assay to see whether ciglitazone and LG100268 have any antiproliferative effects individually or jointly.', 'Academic.', 'None.', 'Culture of immortalized endometrial and endometriotic cell lines with TSA, or ciglitazone or LG100268.', 'PPAR gamma protein expression levels in cells treated with or without TSA, and number of viable cells treated with or without ciglitazone, LG100268, or both.', 'The TSA treatment resulted in up-regulation of PPAR gamma expression in all cell lines in a dose-dependent fashion. Both ciglitazone and LG100268 inhibited proliferation in a dose-dependent manner, and the antiproliferative effects appeared to be synergistic. In addition, endometriotic cells were more sensitive than endometrial stromal cells to LG100268 treatment.\Question: Do peroxisome proliferator-activated receptor-gamma and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells?
answer:
The up-regulation of PPAR gamma induced by TSA indicates that the action of HDACIs also includes the PPAR gamma signaling pathway, suggesting that the activation of PPAR gamma is a desirable way to contain endometriosis phenotypes. The higher sensitivity of endometriotic cells than their endometrial counterpart to LG100268 treatment suggests that the sensitivity differential could be exploited effectively to eradicate unwanted ectopic endometrial tissues while minimizing the collateral damage to the normal endometrial tissues.


question:
Context: The pathogenesis and the clinical impact of diastolic dysfunction (DD) in cirrhosis remain unclear. Our aim was to investigate the factors significantly associated with the presence of DD in patients with decompensated cirrhosis on the waiting list for liver transplantation.', 'consecutive patients with decompensated cirrhosis, who admitted for transplant assessment, were prospectively evaluated. We assessed the independent factors associated with the presence of DD, while their discriminative ability was evaluated by AUC curve. The diagnosis of DD was based on Doppler echocardiography and classified into three categories according to the current guidelines.', 'we evaluated 115 consecutive patients. Sixty six patients (57.3%-group 1) had DD and 49 (42.7%-group 2) had not DD. The 2 groups had similar Child-Pugh/MELD scores and survival. In multivariable logistic regression analysis, pulse rate (OR: 1.082, 95% CI: 1.03-1.15, p = 0.004), and UNa24h (OR: 0.98, 95% CI: 0.97- 0.99, p = 0.004) were the only variables independently associated with the presence of DD. In the subgroup of consecutive patients (n = 31) with evaluation of cytokines, those (n = 22) with DD, compared to those (n = 9) without DD, had significantly higher levels of inteleukin-6 [145 (45-2000) vs. 56 (10-149)pg/mL, p = 0.043].\Question: Is diastolic dysfunction associated with low urinary sodium excretion in patients with decompensated cirrhosis?
answer:

We found that DD was independently associated with lower 24-hour urine sodium. Although no correlation was found between DD and severity of liver disease or survival, further studies are needed for final conclusions.