Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Ex Input:
To determine whether all-trans retinoic acid or a synthetic retinoic acid receptor-α/β-specific agonist, Am80, can reduce the degree of experimental autoimmune optic neuritis in mice with experimental autoimmune encephalomyelitis.', 'Optic neuritis was induced in C57BL/6 mice by immunizing them with myelin oligodendrocyte glycoprotein35-55 . All-trans retinoic acid (350\u2009μg/mouse/time point) or Am80 (5\u2009mg/kg/time point) was administered every other day from day 0 to day 20. The degree of experimental autoimmune encephalomyelitis was scored and histopathological analysis of the optic neuritis was performed on day 22 after the immunization. In vivo-primed draining lymph node cells obtained from vehicle-treated or all-trans retinoic acid-treated mice were stimulated with myelin oligodendrocyte glycoprotein35-55 , and the culture supernatant was collected for assays of interferon-γ and interleukin-17.', 'All-trans retinoic acid treatment significantly reduced the clinical score of experimental autoimmune encephalomyelitis and the severity of the optic neuritis by histopathological analysis. The production of interferon-γ and interleukin-17 was significantly reduced in all-trans retinoic acid-treated mice compared with vehicle-treated mice. Am80 treatment also significantly decreased the severity of the optic neuritis in mice with experimental autoimmune encephalomyelitis.

Ex Output:
0


Ex Input:
Triterpene alcohols and acids are multifunctional compounds widely distributed throughout the plant kingdom that exhibit a variety of beneficial health properties, being synthetic analogs of oleanolic acid under clinical evaluation as anti-tumoral therapeutic agents. However, the antineoplastic activity of two natural occurring triterpenoid alcohols extracted from olive oil, erythrodiol (an intermediate from oleanolic acid), and its isomer, uvaol, has barely been reported, particularly on brain cancer cells. Astrocytomas are among the most common and aggressive type of primary malignant tumors in the neurological system lacking effective treatments, and in this study, we addressed the effect of these two triterpenic diols on the human 1321N1 astrocytoma cell line.', 'Erythrodiol and uvaol effectively affected cell proliferation, as well as cell cycle phases and induced 1321N1 cell death. Both triterpenes successfully modulated the apoptotic response, promoting nuclear condensation and fragmentation. They caused retraction and rounding of cultured cells, which lost adherence from their supports, while F-actin and vimentin filaments disappeared as an organized cytoplasmic network. At molecular level, changes in the expression of surface proteins associated with adhesion or death processes were also observed. Moreover, triterpene exposure resulted in the production of reactive oxygen species (ROS) with loss of mitochondrial transmembrane potential, and correlated with the activation of c-Jun N-terminal kinases (JNK). The presence of catalase reversed the triterpenic diols-induced mitochondrial depolarization, JNK activation, and apoptotic death, indicating the critical role of ROS in the action of these compounds.

Ex Output:
0


Ex Input:
Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.', 'Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms.', 'Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.

Ex Output:

1