Construction of an engineered alpha 1-antitrypsin with inhibitory activity based on theoretical studies

Background: The elastase inhibitor \u3b1-1-antitrypsin (AAT), is a member of the serpin superfamily of protease inhibitors. AAT has a characteristic secondary structure of three-\u3b2-sheets, nine-\u3b1-helices and a reactive central loop (RCL). This protein inhibits target proteases by forming a stable complex in which the cleaved RCL is inserted into \u3b2-sheet-A of the serpin, leading to a conformational change in the AAT protein. Spontaneous polymerization and instability of AAT are challenges with regard to producing drugs against AAT-deficient diseases. Therefore, the purpose of many investigations currently is to produce drugs with lower degrees of polymerization and higher stabilities. In order to investigate the effect of the N-terminal segment (residues 1-43) on AAT structure, molecular dynamic (MD) simulation was used to study structural properties including Root-mean-square deviation (RMSD), internal motions, intramolecular non-bonded interactions and the total accessible surface area (ASA) of native and reduced AAT. These properties were compared in native and truncated AAT. Results: Theoretical studies showed no noticeable differences in the dynamic and structural properties of the two structures. These findings provided the basis for the experimental phase of the study in which sequences from the two AAT constructs were inserted into the expression vector pGAPZ and transformed into Pichia pastoris. Results showed no differences in the activities and polymerization of the two AAT constructs. Conclusions: As small-scale medicines are preferred by lung drug delivery systems, in this study AAT was designed and constructed by decreasing the number of amino acids at the N-terminal region

Psychosocial Adjustment to Illness and Its Relationship with Spiritual Wellbeing in Iranian Cancer Patients

Background. The aim of this study was to investigate the psychosocial adjustment to illness and its relation with spiritual health in cancer patients. Methods. This study was conducted in 2019 in Iran. It was a descriptive study with a sample of 124 cancer patients. Data were collected using two questionnaires of the psychosocial adjustment to illness scale (PAIS) with 46 questions and the Paloutzian and Ellison spiritual health scale with 20 questions. Results. The mean age of the participants in this study was 52.4±13.2 (range 18 to 87 years). The mean months of life with cancer were 16.5 months. The mean score of psychosocial adjustment to illness was 30.7±15.5. The mean score of spiritual wellbeing in the studied patients was 71.4±17.1. The results of the Pearson correlation test showed a significant inverse relationship between the mean score of psychosocial adjustment to illness and the mean score of spiritual wellbeing (p>0.001, rr=−.355). Conclusion. Cancer patients in this study had relatively good psychosocial adjustment with their illness. Spiritual wellbeing can increase psychosocial adjustment to illness in this group of patients