ABSTRACT
Background: Livin, survivin and Pak-1 are all related to the occurrence and development of gastric cancer. Livin and survivin play their roles by inhibiting the activity of caspase-7. Aims: To investigate the expressions and significance of livin, survivin, Pak-1 and caspase-7 in different gastric mucosal lesions. Methods: A total of 45 cases of gastric cancer and paracancerous tissue, 45 chronic atrophic gastritis with intestinal metaplasia, 45 chronic non-atrophic gastritis from Jan. 2015 to Dec. 2019 at the Second Affiliated Hospital of Baotou Medical College were collected. Immunohistochemistry was used to detect the expressions of livin, survivin, Pak-1 and caspase-7, and their correlations with clinicopathological features of gastric cancer patients were analyzed. Results: Compared with chronic non-atrophic gastritis group and paracancerous group, the positivity expression rates of livin, survivin and Pak-1 in intestinal metaplasia group were significantly increased (P<0.05), while caspase-7 was significantly decreased (P<0.05). Compared with intestinal metaplasia group, the positivity expression rates of livin, survivin and Pak-1 in gastric cancer group were significantly increased (P<0.05), while caspase-7 was significantly decreased (P<0.05). Expressions of livin, survivin, Pak-1 and caspase-7 were correlated with the differentiation degree, TNM stage, depth of infiltration and lymph node metastasis in patients with gastric cancer (P<0.05). Conclusions: Livin, survivin, Pak-1 and caspase-7 play important roles in the occurrence and development of gastric cancer.
ABSTRACT
Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.